Category Archives: Gene therapy

Recently, a patient centricity concept has spread across all corners of the healthcare community with a straightforward goal: to improve and save patients lives through innovative and effective drug therapies adapted to patients' individual needs. However, for this concept to truly come to life, it is necessary to count on temperature-controlled supply chain logisticslike CRYOPDP to turn what could be a complex operation into a highly efficient process. This is extremely vital, because a patients life could literally be on the line with every shipment.Patient centricity in the clinical trial community involves meeting the patients where they are.The clinical trial industry is globalising and demands international healthcare logistics partners that can serve its growing and continuously evolving needs. For decades, temperature-controlled logistics experts have operated behind the scenes with patients barely aware of the hard work that went into their medicines journey. Thanks to the Covid-19 vaccine distributions impressive performance and its universal effect on people's health across the globe, it has become apparent to the world just how critical and important a logistics providers mission is for both patients and the industry.The endless pandemic lockdowns meant that patients could not travel to hospital sites for clinical trials due to travel and access restrictions. This led to a seismic shift where sponsors quickly moved to a direct-to-patient model to try to continue trials and keep patient treatments on schedule. As part of our response to this unique situation, CRYOPDP as a specialist in temperature-controlled logistics, with the mission to improve people's healthcare options, had to go further and dive deeper to better understand customers perceptions of the impact of the pandemic and work with them to provide those options.With the patient always at the centre of its business and considering the huge development of decentralised clinical trials, the development and implementation of a new service such as Direct-to-Patientseems to be the most natural evolution for CRYOPDP. We have been offering this turnkey solution completely adapted to patients needs, with the same efficiency and total peace of mind, to the benefit of many customers.This model makes life a lot easier for patients and their families, as they dont have to make multiple trips to a clinic or hospital that is potentially a great distance from their home. It is also beneficial for patients who may be too ill to travel, as well as saves patients time and money.Because of these benefits, the direct-to-patient model has increased clinical trial recruitment by up to 60 percent and helped to maintain patient retention by over 95 percent. Drug developers can also gain access to a larger patient population by onboarding those who are not located near participating hospitals or clinics.Patient centricity becomes more evident with the new generation of cell and gene therapies.From day one, CRYOPDP temperature-controlled logistics solutions have always been essential to improve and save patients lives. But, when speaking about cell and gene therapies in particular, this gains an even more significant meaning.The increase in personalised medicine, advanced therapies, and improved access to healthcare in the developing world are influencing future supply chain solutions development. Cell and gene therapies are enabling the healthcare community to shift the arrow and think about patients in a whole new way.Cell and gene therapies demand rigorous and precise temperature control to ensure that the therapies maintain their viability. And maintaining temperature control calls for flawless implementation and execution.From designing the best transportation route to selecting the correct packaging, every detail is critical to keep product integrity high under all conditions, and for this to happen, the healthcare community can count on CRYOPDP specialists who can meticulously handle the entire supply chain process. We've been supporting the life sciences and healthcare communities and focused on improving patient centricity with innovative temperature-controlled logistics solutions because thinking about the patient and the outcome of our work is what moves and inspires us to be better every day.

In all the geographies of the world that we cover, around 150 countries, we produce an operational performance of 99.96%. And to deliver such operational performance, we count on our employees, the specialists around the globe, to follow our quality standards and protocols in detail, so we can deliver a quality service.

When dealing with patients lives, there is no room for errors. Its all about quality of service making sure that lifesaving samples are distributed on time, within the correct specifications and at the right temperature to ensure the patient's health is never compromised.This commitment has helped CRYOPDP to win numerous industry awards, including Best Clinical Trial Logistics Provider in APAC at the Bioprocessing Excellence Awards 2021 and Most Advanced Healthcare Solution Providers from Europe 2021 by Healthcare Insights Magazine.Our achievements are being recognised across the industry, and as we continue to improve our services for healthcare communities, it will be the end patient that benefits the most.

See the original post:
The Importance of Patient Centricity in Clinical Research and Cell / Gene Therapy Development - Contract Pharma

Purespring Therapeutics

Purespring Therapeutics and SwanBio Therapeutics announce licensing agreement for use of FunSel screening platform

FunSel is Puresprings proprietary in-vivo gene search engine, which allows functional selection of therapeutic factors unconstrained by previous drug discovery bias

SwanBio will use FunSel to advance AAV-based gene therapies for use in neurological diseases

London, UK & Philadelphia, USA 18 July 2022Purespring Therapeutics, a pioneering gene therapy company focused on transforming the treatment of kidney diseases, has entered into a collaborative licensing agreement with SwanBio Therapeutics, a gene therapy company advancing adeno-associated virus (AAV)-based therapies for inherited neurological conditions, for the use of FunSel, Puresprings proprietary gene therapy search engine.

FunSel enables a completely new way of discovering effective biological drugs, removing the narrow, target-focused bias built into traditional drug discovery. FunSel allows functional selection of the most effective factor for disease phenotype correction, starting from a library of thousands of AAV vectors that are selected directly in vivo. All factors in the FunSel library are secreted outside the cells, maximising therapeutic benefit. FunSel is gene and mechanism of action agnostic and is based on the physiology of the organ and disease in question.

Under the terms of the agreement, SwanBio will license the FunSel screening platform from Purespring to explore new targets for early-stage pipeline programs. SwanBio will have an option to develop any targets identified and to own and commercialise any molecules developed. Purespring will be entitled to milestones and royalties upon successful commercialisation. Additional financial terms are not being disclosed.

The FunSel platform has already been instrumental in the creation of Puresprings sister company Forcefield Therapeutics, a pioneer of best-in-class therapeutics to protect heart function, where FunSel was used to discover naturally occurring proteins that retain heart function and help existing cardiomyocytes protect themselves after myocardial infarction.

Story continues

Richard Francis, Chief Executive Officer of Purespring, commented: FunSel brings unique and pioneering screening capabilities and can help deliver the promise of gene therapy to non-monogenic disorders, allowing far broader patient populations to be treated than is the case with most gene therapies. This is the second example of how this gene search engine is helping to underpin a companys development strategy and demonstrates our ability to maximise the value of this platform by sharing this unique capability. SwanBio has a clear mission to develop AAV therapies for neurological disorders and its great to be able to support them and potentially others exploring new targets.

Tom Anderson, Chief Executive Officer of SwanBio, added: FunSel has the potential to enable acceleration and greater precision of candidate selection, and SwanBios application of FunSel has the potential to expand and confirm our early pipeline candidates. SwanBio is committed to advancing AAV-based therapies for the most debilitating neurological disorders and this technology promises to significantly support our ability to refine and further develop potential candidates for development.

- ENDS -

For further information, contact:

Purespring:

Richard Francis, CEOcontact@purespringtx.com+44 (0)20 3855 6324LinkedIn

Consilium Strategic Communications:

Amber Fennell, Jessica Hodgson, Genevieve Wilsonpurespring@consilium-comms.com

SwanBio Therapeutics:

Lara Furstlfurst@swanbiotx.com+1 703 946 0183

Notes to Editors

About Purespring

Purespring is the first company to treat kidney diseases by directly targeting the podocyte, a specialised kidney cell implicated in many kidney diseases, through AAV gene therapy.

Headed by former Sandoz CEO, Richard Francis, Purespring was founded on the work of Professor Moin Saleem, Professor of Paediatric Renal Medicine at the University of Bristol, where he heads a world leading group researching glomerular diseases. Purespring seeks to advance gene therapies for the treatment of both monogenic and non-monogenic chronic renal diseases that are currently poorly addressed with existing treatments.

The company also has a proprietary in-vivo pipeline engine, FunSel, which is a library of all biological factors that could be candidates for gene therapy, combined with a screening method to evaluate these factors in disease models. FunSel allows Purespring to discover new gene therapy candidates across all indications, unconstrained by genetics, to find the right candidate to make the best therapy.

An initial 45 million commitment to Purespring from Syncona Ltd is enabling Purespring to progress its assets to the clinic. Synconas Chief Investment Officer, Chris Hollowood, serves as Chairman. For more information please visit: purespringtx.com and follow us on LinkedIn.

About FunSel

FunSel is a proprietary in vivo gene therapy search engine developed by Purespring Therapeutics co-founder Professor Mauro Giacca, Professor of Cardiovascular Sciences at Kings College, London.

FunSel is gene agnostic: unconstrained by genetics and therefore does not rely on knowledge of which gene is causing a disease. It allows functional selection of therapeutic factors for disease phenotype correction. FunSel contains a library of thousands of AAV vectors encoding secreted proteins.

Because it is gene agnostic, FunSel offers potential to allow the application of gene therapy to non-monogenic disorders and treat much broader patient populations.

The platform has already been instrumental in the creation of Purespring Therapeutics and sister company Forcefield Therapeutics, a pioneer of best-in-class therapeutics to protect heart function and has broad potential for researchers developing gene therapy in many disease areas. It provides Purespring with opportunities to support industry peers through partnering and potential collaborations.

About SwanBio Therapeutics

SwanBio Therapeutics is a gene therapy company that aims to bring life-changing treatments to people with devastating, inherited neurological conditions. SwanBio is advancing a pipeline of gene therapies, designed to be delivered intrathecally, that can address targets within both the central and peripheral nervous systems. This approach has the potential to be applied broadly across three disease classifications spastic paraplegias, monogenic neuropathies, and polygenic neuropathies. SwanBios lead program is being advanced toward clinical development for the treatment of adrenomyeloneuropathy (AMN). For more information, visit SwanBioTx.com.

Read the rest here:
Purespring Therapeutics and SwanBio Therapeutics announce licensing agreement for use of FunSel screening platform - Yahoo Finance

Sekar Kathiresan, MD, Verve Therapeutics co-founder and CEO

Verve Therapeutics has dosed its first patient with what it said today was the first in vivo base editing therapy to reach the clinic, a potential treatment for Heterozygous Familial Hypercholesterolemia (HeFH).

Verve, which specializes in gene editing therapies for cardiovascular disease, said that its VERVE-101 is a single-course gene editing treatment designed to reduce the low-density lipoprotein cholesterol (LDL-C) that drives HeFH.

VERVE-101 consists of an adenine base editor messenger RNA that Verve has licensed from another base editing therapy developer, Beam Therapeutics, as well as an optimized guide RNA targeting thePCSK9gene packaged in an engineered lipid nanoparticle.

By making a single A-to-G change in the DNA genetic sequence ofPCSK9, VERVE-101 aims to inactivate that target gene. Verve reasons that inactivation of thePCSK9gene has previously been shown to up-regulate LDLR expression, leading to lower LDL-C levels and thus reducing the risk for atherosclerotic cardiovascular disease (ASCVD)of which HeFH is a subtype.

Base editing is a pinpoint method for engineering base substitutions without cleaving the DNA double helix backbone. The underlying technology was developed in the lab of Harvard University chemistDavid Liu, PhDwho co-founded Beam with Feng Zhang, PhD, and Keith Joung, MDwith research led by two postdocs,Alexis Komor, PhD, and Nicole Gaudelli, PhD.

Beam is also expected to enroll its first patient later this year in its first clinical trial for one of its base editing therapies, BEAM-101 for the treatment of sickle cell disease (SCD). Beam also plans two IND applications this yearone for its second SCD candidate BEAM-102, and the other for BEAM-201, a treatment for relapsed/refractory T cell acute lymphoblastic leukemia/T cell lymphoblastic lymphoma.

The dosing of the first human with such an investigational base editing medicine represents a significant achievement by our team and for the field of gene editing, Sekar Kathiresan, MD, Verves co-founder and CEO, said in a statement.

Preclinical data suggest thatVERVE-101 has the potential to offer people with HeFH a game-changing treatment option, transforming the traditional chronic care model to a single-course, life-long treatment solution, Kathiresan added.

Andrew Bellinger, MD, PhD, Verves chief scientific and medical officer, added that VERVE-101 is intended to improve upon current standard of care treatment for HeFH. He stated that less than 20% of patients achieve LDL-C goal levels due to the limitations of the chronic model, which include requirements for rigorous patient adherence, regular health care access, and extensive health care infrastructure.

Our ultimate goal withVERVE-101 is to bring a new option to the millions of people with ASCVD around the world, and dosing participants in the Phase I study for this first indication, HeFH, is a key inflection point to achieving that goal, Bellinger said.

Publicly traded Verves stock rose 8% on Tuesday, closing at $22.20.

VERVE-101 is under study in the Phase Ib heart-1 trial (NCT05398029), designed to assess the safety and tolerability ofVERVE-101 with additional analyses for pharmacokinetics and reductions in blood PCSK9 protein and LDL-C.

The trial is designed to enroll approximately 40 adults and includes three parts: A single ascending dose portion, followed by an expansion single-dose cohort where additional participants will receive the selected potentially therapeutic dose, and an optional second-dose cohort, in which eligible participants in lower dose cohorts in Part A have the option to receive a second treatment to reach the selected potentially therapeutic dose.

Verve is conducting the trial at a pair of clinical sites in New Zealand, according to ClinicalTrials.gov.

The company has said it plans to submit both a clinical trial application (CTA) in the United Kingdom and an IND application in the U.S., both in the second half of this year.

Interim clinical data for the heart-1 trialwhich will include safety parameters, blood PCSK9 level and blood LDL-C levelare expected in 2023, Verve said.

Given the once-and-done treatment potential for very large CV [cardiovascular] market opportunities, we seefirst human proof-of-concept data in 2023 for leadVERVE-101 as a key inflection point for the shares, Eun Yang, PhD, an analyst with Jefferies, wrote July 7 in a research note.

In January during a presentation at the 40th Annual J.P Morgan Healthcare Conference, Verve described its market opportunity in CV as potentially hundreds of millions of patients worldwide, including 31 million with a genetic form of ASCVD. Verve presented figures also cited by the National Organization for Rare Disorders (NORD) showing that HeFH affects 1 in 250 people, while HoFH is much rarer, affecting 1 in 250,000, the company said.

VERVE-101 has the potential to change the way cardiovascular disease is cared for by lowering LDL-C as low as possible for as long as possible after a single treatment, Bellinger added.

Given the once-and-done treatment potential for very large CV [cardiovascular] market opportunities, we seefirst human proof-of-concept data in 2023 for leadVERVE-101 as a key inflection point for the shares, Eun Yang, PhD, an analyst with Jefferies, wrote July 7 in a research note.

Verve is also developing a second program designed to lower blood lipids such as LDL-C by permanently turning off theANGPTL3gene in the liver, in order to treat homozygous familial hypercholesterolemia (HoFH), a rare genetic subtype of ASCVD characterized by extremely high blood LDL-C, as well as for patients with ASCVD who have not achieved goal LDL-C lowering with oral therapy and a PCSK9 inhibitor.

The company expects to identify its base editing development candidate targeting ANGPTL3 and begin IND-enabling studies later this year.

Since 2019, Verve had licensed Beams technology for human therapeutics against PCSK9 and three other liver-mediated, cardiovascular disease targets, including ANGPTL3, plus two undisclosed gene targets.

Just last week, Verve and Beam amended their agreement to develop and commercialize products targeting another liver-mediated, cardiovascular disease target, though that target and development timeline have not been disclosed.

Verve agreed to oversee development and commercialization of products targeting that gene, with Beam holding options to co-develop them after the final dosing of a patient in a Phase I clinical trial. If Beam opts in, it would share 35% of worldwide development expenses for the product, as well as jointly commercialize and share 35% of the profits and expenses of commercializing that product worldwide.

But if Beam doesnt opt in, it would be entitled to receive milestones and royalties as called for in the companies original agreement.

The amended agreement does not change Beams co-development option for Verves programs targeting PCSK9 and ANGPTL3. BEAM has the option to co-develop those programs at the end of Phase I. If Beam exercises that option, it would fund 33% of major market development costs and 50% of U.S. commercialization costsbut in return would receive 50% of U.S. profits, whileVerve wouldretain ex-US rights. For those ex-U.S. opt-in products, on aproduct-by-productbasis, Verve agreed to pay Beam clinical and regulatory milestones of up to $5.6million and sales-based milestones of up to $7.5million.

If Beam declines to opt in, it would be eligible instead for $11.3 million per product in payments tied to achieving development milestones, $15 million per product in sales milestone payments and royalties in the low single digits.

Verve finished the first quarter with cash, cash equivalents and marketable securities of $323.3 million as of March 31, 2022, down 10% from $360.4 million as of December 31, 2021.

Based on current operating plans, Verve expects its existing cash, cash equivalents and marketable securities will enable the company to fund its operating expenses and capital expenditure requirements into 2024, Verve said in May when it reported Q1 results.

Read more from the original source:
Verve Therapeutics Doses First Patient with In Vivo Base Editing Therapy - Genetic Engineering & Biotechnology News

Cergentis is a cornerstone acquisition that expands Solvias' solutions supporting complex and emerging therapies.

According to pharmaceutical market intelligence provider, Evaluate, global sales of cell and gene therapies are projected to accelerate at a 63% compound annual growth rate through 2026. As more researchers leverage emerging genetic engineering techniques to develop complex, novel medicines, they require sophisticated solutions to analyze their safety and effectiveness.

With the addition of Cergentis, Solvias supports the increasing number of global pharmaceutical, biotech, and contract development and manufacturing organizations developing genetically engineered therapies with an expanded platform of testing services highlighted by:

Archie Cullen, CEO, Solvias, stated:"We are relentlessly focused on ensuring the safety of new therapies in development. Cergentis is a cornerstone acquisition that expands our solutions supporting complex and emerging therapies. We will continue to pursue strategic acquisitions that add specialized capabilities to our offering and advance our goal of being a forerunner in our industry."

Joris Schuurmans, CEO, Cergentis, added:"We are excited to become part of a global leader that complements our scientific expertise, innovation and customer service. Solvias and Cergentis share a deep commitment to providing our customers with the highest quality solutions and support to safely get their products into the hands of patients who need them."

Effective immediately, Mr. Schuurmans will join Solvias' leadership team and continue to lead operations for Cergentis.

Cergentis marks Solvias' second acquisition since partnering with health care investors Water Street Healthcare Partners and JLL Partners in 2020. The company has recruited industry leaders to join its board and commenced a program to significantly upgrade and expand its information technology platform and infrastructure to support its plans for global expansion.

Financial terms of the acquisition are not being disclosed. Achelous Partners served as the advisor to Cergentis on the transaction.

About CergentisCergentis is a trusted genomics-focused biotechnology company providing services and in-house solutions based on its proprietary genomic analysis platform to all leading biopharmaceutical companies and renowned research institutes. With widely published and recognized genetic analyses, Cergentis supports a global customer base in the characterization and QC of genetically engineered models, biopharmaceutical cell line development, and cell- and gene therapy products. By helping to de-risk R&D program decisions, minimizing time-to-clinic, providing objective genomic evidence for regulators, and supporting patient safety, Cergentis aims to support biopharmaceutical medicine development programs worldwide. For more information, visit cergentis.com.

About Solvias AGSolvias is a worldwide leader in contract research, development and manufacturing for the pharmaceutical, biotech, material science and cosmetic industries. Drawing on 20 years of scientific excellence, the company provides flexible and scalable analytical and manufacturing solutions that ensure the integrity of pharmaceutical and medical device products across their life cycle. Headquartered in Kaiseraugst near Basel, Switzerland, Solvias and its laboratories operate to the highest standards and in accordance with ISO, GMP, GLP and FDA regulations. For more information, visit solvias.com.

SOURCE Solvias

Read the original:
Solvias Acquires Cergentis to Bolster Biologics and Cell & Gene Therapy Capabilities - PR Newswire

Plain Language Summary

Hemophilia is a bleeding disorder where blood does not clot normally because of a genetic mutation that causes missing or defective clotting protein. People with severe hemophilia have painful spontaneous bleeding in their joints, which can lead to chronic pain and disability. Gene therapy, which introduces the instructions to make the missing/defective clotting protein and prevent spontaneous bleeding, is being investigated as a potential treatment for severe hemophilia. Gene therapy for severe hemophilia A is a new treatment that is much different from standard, intensive hemophilia treatments. The Haemo-QOL-A questionnaire is used to evaluate health-related quality of lifein people with hemophilia on standard treatments. In this manuscript, we determine whether the Haemo-QOL-A questionnaire can be used to evaluate change in quality of lifefor people with severe hemophilia A after receiving gene therapy. Using data from previous clinical trials of the gene therapy valoctocogene roxaparvovec (AAV5-hFVIII-SQ), we show that the Haemo-QOL-A did measure a change in quality of life after gene therapy. We also estimate how much change in Haemo-QOL-A scores from before to after gene therapy represents a clinically meaningful improvement in quality of life. This threshold can be used in future research evaluating the effects of gene therapy on quality of life for people with hemophilia. While the results of this study are important, only 23 people were included in the analysis. To confirm our results, future analyses with larger numbers of participants are needed.

Hemophilia is a genetic bleeding disorder caused by deficiency or inactivity of factor VIII (FVIII; hemophilia A) or factor IX (hemophilia B) protein. Hemophilia A accounts for approximately 80% of hemophilia cases worldwide.1 Severe hemophilia A (FVIII <1 IU/dL) is characterized by recurrent and spontaneous musculoskeletal bleeding episodes, resulting in joint damage, mobility issues, and early mortality.1 People with severe hemophilia A (PWSHA) experience significant health-related quality of life (HRQOL) impairment, including negative effects on emotional and cognitive health, joint pain, poor functioning in school, and difficulties securing and maintaining employment.27

Treatment options for hemophilia A are rapidly evolving. Standard of care for PWSHA is prophylactic factor replacement therapy using exogenous FVIII or bypassing agents such as emicizumab-kxwh.1,8 Factor replacement therapy must be administered frequently through intravenous infusions (14 infusions/week), resulting in substantial treatment burden and potential risk of breakthrough bleeding following poor treatment adherence.9 Despite prophylactic treatment, most PWSHA still require on-demand treatment with FVIII or emicizumab to treat bleeding episodes.10

Gene therapies using recombinant adeno-associated viral (AAV) vectors carrying human FVIII gene may offer a novel approach to hemophilia A treatment.1113 In phase 1/2 and phase 3 studies, a 61013 vg/kg infusion of valoctocogene roxaparvovec, an investigational gene therapy utilizing a codon-optimized AAV serotype 5 vector encoding a B-domaindeleted human FVIII (AAV5-hFVIII-SQ), resulted in clinically relevant reductions in annualized treated bleed rate and exogenous FVIII replacement up to 5 and 1 years of follow-up, respectively.11,12,14,15 If long-term efficacy of viral vector gene transfer is established, it could represent a paradigm shift in hemophilia A treatment.

The general health questionnaire EuroQOL-5D-5L (EQ-5D-5L) is used to evaluate overall HRQOL.16 However, people with hemophilia completing the EQ-5D-5L reported higher health states than the general population, indicating the presence of a disability paradox in PWSHA.17 Thus, HRQOL assessment with the EQ-5D-5L scores may not accurately reflect the hemophilia-related burden they experience.18 To address the need for a reliable HRQOL assessment, the hemophilia-specific HRQOL questionnaire for adults (Haemo-QOL-A) was developed.19 It consistently performs well among adults relative to other hemophilia-specific questionnaires, demonstrating robust validity in people undergoing standard treatment regimens.2023

Gene therapy is a novel, potentially one-time intervention. To date, HRQOL has been evaluated only in a small number of PWSHA receiving gene therapy.14 It is unclear how gene therapy will incrementally benefit the HRQOL for PWSHA compared with standard of care or whether the Haemo-QOL-A will be an appropriate measure to detect HRQOL changes after gene therapy.24 Thus, in addition to estimating Haemo-QOL-A clinically important differences (CID) specifically for gene therapy recipients, this post hoc analysis of phase 1/2 and phase 3 clinical trial data aimed to evaluate the content validity, construct validity, and reliability of the Haemo-QOL-A for measuring HRQOL in adult PWSHA treated with gene therapy.

A post hoc psychometric analysis to determine the content validity, construct validity and reliability of the Haemo-QOL-A was conducted using data from a phase 1/2 open-label dose-escalation study (Clinicaltrials.gov, NCT02576795; EudraCT, 2014-003880-38)12 and phase 3 open-label, single-arm study (NCT03370913, EudraCT, 2017-003215-19) to evaluate the efficacy and safety of valoctocogene roxaparvovec in adult PWSHA.15 Full study design details have been published previously.11,12,14,15 All protocols were reviewed and approved by local institutional review boards or ethics panels and conducted according to the Declaration of Helsinki; all participants provided informed consent.

All participants were male and 18 years old with severe hemophilia A (FVIII levels 1 IU/dL). The phase 1/2 dose-escalation study included participants on FVIII prophylaxis or on-demand therapy who had 12 bleeding episodes within 12 months prior to enrollment; participants received an infusion of AAV5-hFVIII-SQ at 61012 vg/kg, 21013 vg/kg, 41013 vg/kg, or 61013 vg/kg. The ongoing phase 3 study included participants from 48 sites worldwide who were on prophylactic FVIII replacement therapy for 12 months prior to enrollment; all participants received an infusion of 61013 vg/kg AAV5-hFVIII-SQ.

Data from up to 3 years of follow-up for participants in the phase 1/2 study who received 61013 vg/kg dose of AAV5-hFVIII-SQ were used. The phase 3 study intention-to-treat (ITT) population was defined as all enrolled and treated participants, and the modified ITT (mITT) population was defined as all treated participants who were human immunodeficiency virus (HIV)-negative and who completed the week 26 visit. Data up to 26 weeks from both populations were used in these analyses.

Patient HRQOL was assessed using the Haemo-QOL-A questionnaire in both study populations, administered at baseline and at weeks 1, 2, 3, 4, 16, 28, 52, 78, 104, 130, and 156 in the phase 1/2 study population and at baseline and weeks 4, 12, and 26 in the phase 3 study population. The EQ-5D-5L was administered in the phase 3 study at baseline and weeks 4, 12, and 26.

The 41 items on Haemo-QOL-A include the domains of Consequences of Bleeding (7 items), Emotional Impact (6 items), Physical Functioning (9 items), Role Functioning (11 items), Treatment Concern (3 items), and Worry (5 items). Items were scored on a 6-point Likert-type scale with higher scores indicating better HRQOL or less impairment. Subscale scores for each disease domain range from 0 to 5 and the Total Score ranges from 0 to 30. Both domain and total raw scores are transformed to a 0 to 100 scale using the formula:

Domain scores were imputed using mean domain scores if <50% of items were missing. Total Score was not calculated, and no imputations were performed if >50% of items were missing. Change in scores at specific time points were calculated using the formula:

EQ-5D-5L was used to assess general health status for the 5 domains of Mobility, Self-care, Usual Activities, Anxiety and Depression, and Pain and Discomfort. Items on EQ-5D-5L were scored on a scale of 1 to 5 with higher scores representing increased impairment. The EQ-5D-5L vertical visual analog scale (VAS) of current health status scores were assessed on a scale ranging from 0 to 100, with higher scores indicative of better HRQOL.

Statistical analyses were performed using IBM SPSS Statistics 25 (IBM Corporation, Armonk, NY). Data normality was assessed graphically using frequency distribution histograms and statistically using skewness, kurtosis, and standard error. Categorical variables were described using frequencies and percentages. Continuous variables with normal distribution were assessed using descriptive statistics of mean standard deviation (SD) or range. Variables with non-normal distribution were assessed using mean SD and median (interquartile range [IQR]). Significance was assessed at <0.05 (2-tailed) with 95% confidence intervals (CIs).

Item facility, which assesses the possible presence of floor or ceiling effects, was calculated using data from the phase 1/2 study and the phase 3 ITT study populations. An item was considered to have floor or ceiling effects and poor item facility if >50% of reported responses for items were either the minimum/maximum option.25

Convergent validity, which assesses the degree of correlation with existing measures for a condition, was measured by correlating Haemo-QOL-A scores with EQ-5D-5L scores in participants treated in the phase 3 mITT study population. Spearmans Rank correlation coefficients were calculated between Haemo-QOL-A Total and domain scores vs EQ-5D-5L domain scores at baseline and week 26. Spearmans Rank correlation coefficients were calculated to assess the relationship between Haemo-QOL-A Total and domain score change and score change vs EQ-5D-5L domain score changes from baseline to week 26 in the phase 3 study. Pearsons Rank correlation coefficient was calculated between Haemo-QOL-A Total and domain score changes vs EQ-5D-5L VAS score changes. Regression analyses were also conducted to evaluate the relationship between the 2 instruments when assessing Haemo-QOL-A vs EQ-5D-5L score change from baseline to week 26 (change on change).

Discriminant validity is the ability of a scale to distinguish between different patient subgroups and was assessed by comparing groups of participants from the phase 3 mITT study population based on baseline EQ-5D-5L VAS scores. Independent sample t-tests were used to compare participants with baseline EQ-5D-5L VAS scores >87.15 vs <87.15 (the UK population norm for males aged 2535).26 Data from baseline and week 26 were pooled in order to compare mean Haemo-QOL-A Total and domain scores for participants with baseline EQ-5D-5L VAS scores >87.15 vs those with baseline EQ-5D-5L VAS scores <87.15.

Item discrimination and internal consistency, which assess the ability of an item to discriminate against others on its subscale, were calculated using data from the phase 1/2 study population and the phase 3 ITT study population. Item discrimination was predicted using Spearmans Rank correlation coefficient between individual item scores and Total Score. Cronbachs alpha and squared multiple correlation were used to calculate internal consistency. Items with Cronbachs alpha >0.7 were considered to have properties of internal consistency.

For QOL evaluation in chronic disease, half SD of baseline mean is used to determine a distribution-based estimate of the CID threshold.27 We estimated the CID via distribution methods; the half SD rule (of baseline) was applied for Haemo-QOL-A Total and domain scores.

Given the small sample size and large range of changes in EQ-5D-5L VAS score (ie, 25 to +25), different anchor methods were sequentially deployed to provide the most accurate CID estimate. Data from the phase 1/2 study population were not used since the EQ-5D-5L was not administered to study participants. The mean difference in Haemo-QOL-A Total Score change from baseline to week 26 was calculated between the following categories of participants based on their EQ-5D-5L VAS score change from baseline to week 26 in the phase 3 mITT study population:

a. Participants with VAS score change +3.

b. Participants with a VAS score change between +3 and 3.

c. Participants with VAS score change 3.

Next, results from regression analyses were extrapolated to predict change in Haemo-QOL-A Total Score (dependent variable) vs an EQ-5D-5L VAS score increase of 3. Then, the mean difference in Haemo-QOL-A Total and domain score changes from baseline to week 26 were calculated between categories of participants based on their EQ-5D-5LVAS score change from baseline to week 26 shown in Table 1. Between those categories, the relative magnitude of EQ-5D-5LVAS score change was mapped against relative magnitude of Haemo-QOL-A score change to derive the mean change in Haemo-QOL-A score vs EQ-5D-5L VAS score change of 1 and 3, respectively.

Table 1 EQ-5D-5L VAS Score Change Categories Used in Anchor-Based Estimation of Clinically Important Difference

Haemo-QOL-A data were analyzed from 7 participants in the phase 1/2 study through 156 weeks and 16 participants in the phase 3 study through 26 weeks (mITT = 16). Mean (SD) age was 30.4 (5.8) years and 29.7 (6.2) years for participants in the phase 1/2 and 3 trials, respectively.11,12,15

Baseline Haemo-QOL-A scores were similar in the phase 1/2 and phase 3 studies (Table 2). In the phase 3 mITT study population, both EQ-5D-5L VAS and Haemo-QOL-A Total Scores at week 26 were higher than at baseline, suggesting an improvement in HRQOL of participants following AAV5-hFVIII-SQ infusion (Table 3; Supplemental Figure 1).

Table 2 Mean Change from Baseline in Haemo-QOL-A Total and Domain Scores in the Phase 1/2 and 3 Studies

Table 3 Mean Transformed Haemo-QOL-A Total Score and EQ-5D-5L VAS Scores at Baseline and Week 26 by EQ-5D-5L VAS Score Change Subgroups

Items where >50% of responses were reported as the minimum/maximum response were considered to have poor items facility (ie, floor or ceiling effects). Out of 41 items, 13 had ceiling effects (Supplemental Table 1). The domains with the highest percentage of items with ceiling effects were Treatment Concern (2/3 items) and Emotional Impact (3/6 items). No floor effects were observed.

Our results indicate good convergent validity between the Haemo-QOL-A and EQ-5D-5L. Overall, Haemo-QOL-A Total and domain scores were inversely correlated with EQ-5D domain scores demonstrating that as degree of impairment in Mobility, Self-care, Usual Activities, Anxiety and Depression, and Pain and Discomfort decrease (demonstrating improvement), Haemo-QOL-A scores increase (demonstrating improvement), and vice versa.

The strongest correlations were seen when comparing week 26 and change vs change scores. In both cases, the Pain and Discomfort domain of the EQ-5D-5L was strongly and significantly correlated with the Haemo-QOL-A. At week 26, the strongest correlations were seen between Role Functioning and Pain and Discomfort (0.87, P <0.01), Emotional Impact and Pain and Discomfort (0.85, P <0.01), Physical Functioning and Pain and Discomfort (0.79, P <0.01), and Total Score and Pain and Discomfort (0.87, P <0.01) (Supplemental Table 2). When comparing change in Haemo-QOL-A to EQ-5D-5L scores, the strongest correlations were seen between Emotional Impact and Anxiety and Depression (0.88, P <0.01), Emotional Impact and Pain and Discomfort (0.7, P <0.01), Physical Functioning and Pain and Discomfort (0.73, P <0.01), Total Score and Anxiety and Depression (0.82, P <0.01), and Total and VAS scores (0.77, P <0.01), implying that improvement in Physical Functioning and Emotional Impact are being driven by a decrease in pain (Table 4). At baseline, the strongest correlations were between Physical Functioning domain of the Haemo-QOL-A and the Usual Activities (0.75, P <0.01) and Pain and Discomfort (0.64, P <0.01) domains of EQ-5D-5L (Supplemental Table 3). Regression analyses showed a linear correlation between change in Haemo-QOL-A Total Scores and EQ-5D-5L VAS scores (Figure 1), with a predicted change of 0.63 in Haemo-QOL-A Total Score for every EQ-5D-5L VAS score change of 1 (R2 = 0.5, adjusted R2 = 0.46).

Table 4 Correlations Between Change from Baseline to Week 26 in Haemo-QOL-A Transformed Scores and Corresponding Change in EQ-5D-5L Scores, Modified Intent-to-Treat Population, Phase 3 Study

Figure 1 Linear regression plot of change in Haemo-QOL-A Total Score vs change in EQ-5D-5L VAS scores, from baseline to week 26, modified intent-to-treat population, phase 3 study.

Abbreviations: EQ-5D-5L, EuroQOL-5D-5L; Haemo-QOL-A, hemophiliaspecific healthrelated quality of life questionnaire for adults; TS, total score; VAS, visual analog scale.

There was a substantial difference between mean Haemo-QOL-A scores reported by participants with an EQ-5D-5L VAS score change of magnitude <3 vs those with an EQ-5D-5L score change of magnitude 3 (Table 3). Good discriminant validity was demonstrated by a mean difference between participants with EQ-5D-5L scores above and below the UK population norm ranging from 6.4617.31. The Haemo-QOL-A Total Score (mean [CI] difference 11.81 [20.2, 3.4], P = 0.01) and domains scores for Emotional Impact (17.3 [26.4, 8.2], P = 0.001) and Role Functioning (15.4 [24.6, 6.2], P = 0.002) were most sensitive to discriminate differences in impairment based on EQ-5D-5L scores (Figure 2).

Figure 2 Difference between mean Haemo-QOL-A Total and domain scores in EQ-5D-5L VAS participant subgroups (UK population norm [n = 9]), modified intent-to-treat population, phase 3 study. an = 23 for VAS score

Abbreviations: EQ-5D-5L, EuroQOL-5D-5L; Haemo-QOL-A, hemophiliaspecific healthrelated quality of life questionnaire for adults; VAS, visual analog scale.

Additionally, review of participant-level data indicated a relationship between clinical outcomes (eg, ongoing arthropathy, bleeds and comorbidities) and Haemo-QOL-A scores, suggesting that the tool can discriminate between different disease states. In the phase 3 study population, 3/15 participants reported HRQOL score decreases greater in magnitude than the instrument CID estimate. All 3 participants had degenerative joint damage alongside other comorbidities. Of the 4/15 participants who reported Haemo-QOL-A score changes lower in magnitude than the CID estimate, 3 had ongoing arthropathy. Of the 8 participants that reported score increase >CID, only 3 had arthropathy.

Of the 41 items in Haemo-QOL-A, 38 had corrected item-total correlation scores >0.4. Three items were identified as non-discriminatory in their domain (corrected item-total correlation scores <0.4). The item I am able to complete household tasks in the Physical Functioning domain had a corrected item-total correlation of 0.03. However, the domain showed good internal consistency overall, and although deletion of this item improved Cronbachs alpha, it improved from an acceptable level regardless (from 0.71 to 0.76). In addition, 2 of 3 items in the Treatment Concern domain, I worry about the safety of my treatment and I worry about the availability of hemophilia products, had poor discrimination (item correlation-total scores 0.09 and 0.26, respectively). Overall, the domain showed poor internal consistency and deletion of each item only improved the Cronbachs alpha for this domain from 0.31 to 0.42 and 0.317, respectively.

Results of the distribution-based method to estimate CID in Haemo-QOL-A are shown in Supplemental Table 4. A variety of anchor-based methods were also tested. For participants with EQ-5D VAS score change categories of +3, between +3 and 3, and 3, the mean changes in Haemo-QOL-A Total Scores were 16.3, 1.8, and 2.8, respectively (Table 3). Comparison of groups indicated a score change 6.31 would represent a clinically meaningful change in the Haemo-QOL-A Total Score. However, as the mean VAS score change in the groups experiencing a score change 3 (ie a clinically meaningful change in VAS28) is far greater than the CID threshold for the VAS (mean score change of 13), it is likely that the true CID is <6.31; thus, further analyses were conducted and detailed below. First, results from regression analyses were extrapolated to predicted change in Haemo-QOL-A Total Score (dependent variable) vs EQ-5D VAS score increase of 3. Analyses predicted that for each 1-point increase in VAS score, Haemo-QOL-A Total Score would increase by 0.63. Therefore, a 3-point VAS score change should equate to a Haemo-QOL-A Total Score change of 1.89. Next, given the distribution of the available data, mean change in Haemo-QOL-A Total and domain scores were mapped against reported VAS change categories shown in Table 1 that were greater in magnitude than the accepted CID of 3.28 An average of all domain CID estimates was calculated to give an overall estimate for what would constitute a CID score change for the domains of the Haemo-QOL-A (Supplemental Table 5). The resultant Haemo-QOL-A Total Score CID estimate (score change 5.5 in magnitude) was lower than the estimated domain score (score change 6.0 in magnitude) due to lack of relevance of 2/3 items in the Treatment Concern domain in patients treated with gene therapy. Given the distribution of the data and small sample size, the latter anchor analyses in Supplemental Table 5 were deemed most reliable. This is further corroborated by the fact that the Haemo-QOL-A Total Score CID estimate derived from this method matches others that use a distribution-based method.

Participants in the phase 1/2 and 3 studies had higher mean Haemo-QOL-A Total Score change from baseline than the CID estimate at weeks 28, 52, 104, and 156 post-infusion and at week 26 post-infusion, respectively (Table 2). Similarly, participants reported clinically meaningful improvements in the domain scores for Consequences of Bleeding, Physical Functioning, Role Functioning, and Worry at all time points (Table 2). Changes in mean domain scores for Emotional Impact and Treatment Concern were not consistently above the CID threshold in the phase 1/2 study population (Table 5).

Table 5 Mean Change in Transformed Haemo-QOL-A Scores for Domains of Emotional Impact and Treatment Concern, Phase 1/2 Study

This is the first study to psychometrically validate the Haemo-QOL-A in PWSHA undergoing gene therapy. Validation of Haemo-QOL-A is important to inform clinical analysis of the effect of gene therapy on HRQOL. Our preliminary results demonstrate good psychometric validity of the Haemo-QOL-A when measured in participants undergoing gene therapy, consistent with the US Food and Drug Administration guidelines for patient-reported outcome instrument validation, though all results should be interpreted with caution and confirmed in a larger sample size.29

In this study, the Haemo-QOL-A had good preliminary construct validity, including convergent validity, as there was a high degree of correlation between the Haemo-QOL-A and EQ-5D-5L. Despite the limited sample size, mean Haemo-QOL-A Total and domain scores were capable of detecting differences in participant populations with vs without a high burden of disease, suggesting the instrument had good discriminant validity. The scale also showed good content validity with very few items displaying floor and ceiling effects, except in the Treatment Concern domain, where 2/3 questions are not relevant to an individual undergoing gene therapy in a clinical trial. Our results also establish CIDs in Haemo-QOL-A scores after gene therapy and demonstrate likely applicability in ongoing clinical studies.

Convergent validity preliminarily identified significant correlations between Haemo-QOL-A and EQ-5D-5L scores at both baseline and week 26. Correlations at baseline, although significant, were not as strong as at week 26, highlighting the disability paradox experienced by PWSHA.17 Improved outcomes on the Haemo-QOL-A Total Scores and domains of Emotional Impact, Physical Functioning, and Treatment Concern at week 26 post-infusion were inversely correlated with EQ-5D-5L domain scores for Usual Activities, Anxiety and Depression, and Pain and Discomfort. There were no significant correlations between the EQ-5D-5L domain of Mobility and the Haemo-QOL-A domain of Physical Functioning, suggesting that improvements in physical QOL of participants treated with gene therapy may be driven largely by a decrease in pain.

Mean Haemo-QOL-A Total Scores discriminated well among our limited sample of study participants with differing degrees of HRQOL impairment based on EQ-5D-5L VAS scores. Previous studies show similar discrimination between hemophilia A populations differing in disease severity, HIV status, and type of treatment (on-demand vs prophylaxis) using Haemo-QOL-A.19 The current analysis used general population scores based on UK norms.26 It will be interesting to evaluate the discriminant characteristics of Haemo-QOL-A in studies conducted in different geographic regions. Additionally, the tool discriminated between participants with and without ongoing arthropathy in our limited sample of study participants, suggesting that joint damage and subsequent pain heavily impact HRQOL in PWSHA; therefore, treatment should aim to prevent joint damage before it occurs.

Of the 6 Haemo-QOL-A domains, only Treatment Concern had poor internal consistency. Two items relating to treatment safety and availability lacked discrimination. The third item on concerns regarding clinician inexperience performed well. Thus, two-thirds of this domain was insensitive to the psychological HRQOL of participants pertaining to their treatment, which lowered the Haemo-QOL-A Total Score. Since a one-time infusion of gene therapy may circumvent the need for repeated factor infusions, participants may not be as concerned about treatment availability. Further, since gene therapy is provided through specialist treatment centers with thorough follow-up, participants may not be as concerned about the safety of their treatment. In the future, the Treatment Concern domain could be revised to be more appropriate for evaluating change post-gene therapy by, for example, using the remaining item I worry about the safety of my treatment to score the domain or adding additional questions that better reflect the current treatment landscape.

A total of 13 items showed ceiling effects. These were most prevalent in the Treatment Concern and Emotional Impact domains. Floor and ceiling effects diminish sensitivity of psychometric instruments and can result in underestimation of treatment effectiveness. Scores pertaining to these items must therefore be interpreted cautiously in future applications of Haemo-QOL-A in gene therapy.

It is important to benchmark HRQOL improvements in participants undergoing gene therapy for hemophilia A against CID estimates generated using both distribution- and anchor-based approaches. The current study used both methods to establish CID estimates that are in line with those previously published following FVIII prophylaxis, where the distribution-based CID estimate for Haemo-QOL-A Total Score ranged from 5 to 7 and that of the Physical Functioning domain ranged from 6 to 9.30 However, given the small number of participants receiving gene therapy in the current analysis and the vastly different nature of the HRQOL burden experienced by participants receiving gene therapy vs those receiving standard of care, clinicians should be cautious in comparing the magnitude of CID scores across these 2 studies.

Small sample size was a limitation in both populations, which precluded using several anchor-based estimation approaches.28 A low anchor magnitude of 3-point EQ-5D-5L VAS score change was adopted given the EQ-5D-5Ls limitation in determining differences in disease state in hemophilia.17 Of all participants evaluated across both populations, 4 reported baseline Total Score >85%, indicating possible ceiling effects. Here, some participants reported VAS scores higher than population norms; other research using the EQ-5D-5L in PWSHA found similar results, suggesting a disability paradox.17 People with chronic conditions often report higher or similar health state valuations than the general population,31,32 in part due to processes of adjustment and coping. A larger sample size may provide more meaningful anchor scores and allow more accurate estimation of CID.

Future availability of novel gene therapy interventions will likely shift the paradigm of hemophilia A treatment. This small study is the first to validate the Haemo-QOL-A for detecting clinically meaningful improvement in the HRQOL of PWSHA receiving gene therapy. Our analyses establish initial CID estimates and support the validity and reliability of the Haemo-QOL-A for measuring changes in HRQOL. These preliminary findings suggest that the Haemo-QOL-A is likely fit for evaluating HRQOL and provides a guide for future applications for measuring HRQOL outcomes in PWSHA following gene therapy. Prospective studies with larger sample sizes are needed to evaluate this instrument in a broader severe hemophilia A population.

De-identified individual participant data underlying these results (including text, tables, figures, and appendices) will be made available, together with the clinical protocol and data dictionaries, for non-commercial, academic purposes. Additional supporting documents may be available upon request. Investigators will be able to request access to these data and supporting documents via the Publication Data Request page at http://www.BioMarin.com beginning 6 months and ending 2 years after publication. Data associated with any ongoing development program will be made available within 6 months after approval of the relevant product. Requests must include a research proposal clarifying how the data will be used, including proposed analysis methodology. Research proposals will be evaluated relative to publicly available criteria available at http://www.BioMarin.com to determine if access will be given, contingent upon execution of a data access agreement with BioMarin Pharmaceutical Inc.

The protocol for the 201 trial was reviewed and approved by the Imperial College Research Ethics Committee at Imperial College London and the ethics committees of all other participating sites. The protocol for the 301 trial was reviewed and approved by the Research Ethics Committee at the State University of Campinas and the institutional review boards or ethics committees of all other participating sites. Both studies were conducted in accordance with the guidelines outlined in the Declaration of Helsinki. All participants in both trials provided written informed consent prior to participating in any protocols.

We thank the study participants, study site personnel, and investigators who were involved in these clinical trials. We thank Nina Mitchell of BioMarin Pharmaceutical Inc., for her contributions to this project. Project management support was provided by Sara Hawley of BioMarin Pharmaceutical Inc. Medical writing support was provided by Kathleen Pieper, PhD, and Atreju Lackey, PhD, of AlphaBioCom, LLC, and funded by BioMarin Pharmaceutical Inc.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising, or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding for this research was provided by BioMarin Pharmaceutical Inc.

Jennifer Quinn was an employee and stockholder of BioMarin Pharmaceutical Inc., London, UK at the time of the study. Wing Yen Wong and Kathleen A Delaney are employees of BioMarin Pharmaceutical Inc., Novato, CA, USA. Wolfgang Miesbach has received speaker honoraria and project grants from Bayer, BioMarin Pharmaceutical Inc., Biotest, CSL Behring, Chugai, Freeline, LFB, Novo Nordisk, Octapharma, Pfizer, Roche, Sanofi, Sobi, Takeda/Shire, and uniQure. Monika Bullinger has received speaker honoraria and project grants from Bayer, BioMarin Pharmaceutical Inc., Janssen Cilag, Otsuka Lundbeck, and Pfizer. The authors report no other conflicts of interest in this work.

1. Srivastava A, Santagostino E, Dougall A, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26(Suppl 6):1158. doi:10.1111/hae.14046

2. Barr RD, Saleh M, Furlong W, et al. Health status and health-related quality of life associated with hemophilia. Am J Hematol. 2002;71(3):152160. doi:10.1002/ajh.10191

3. Forsyth AL, Witkop M, Lambing A, et al. Associations of quality of life, pain, and self-reported arthritis with age, employment, bleed rate, and utilization of hemophilia treatment center and health care provider services: results in adults with hemophilia in the HERO study. Patient Prefer Adherence. 2015;9:15491560. doi:10.2147/PPA.S87659

4. Limperg PF, Haverman L, Maurice-Stam H, et al. Health-related quality of life, developmental milestones, and self-esteem in young adults with bleeding disorders. Qual Life Res. 2018;27(1):159171. doi:10.1007/s11136-017-1696-0

5. Witkop M, Neff A, Buckner TW, et al. Self-reported prevalence, description and management of pain in adults with haemophilia: methods, demographics and results from the pain, Functional Impairment, and Quality of life (P-FiQ) study. Haemophilia. 2017;23(4):556565. doi:10.1111/hae.13214

6. Mercan A, Sarper N, Inanir M, et al. Hemophilia-specific quality of life index (Haemo-QoL and Haem-A-QoL questionnaires) of children and adults: result of a single center from Turkey. Pediatr Hematol Oncol. 2010;27(6):449461. doi:10.3109/08880018.2010.489933

7. Ozelo M, Chowdary P, Regnault A, Busk A. Impact of severe haemophilia A on patients health status: results from The Guardian 1 clinical trial of turoctocog alfa (NovoEight). Haemophilia. 2015;21(4):451457. doi:10.1111/hae.12617

8. Oldenburg J, Mahlangu JN, Kim B, et al. Emicizumab prophylaxis in hemophilia A with inhibitors. N Engl J Med. 2017;377(9):809818. doi:10.1056/NEJMoa1703068

9. Thornburg CD, Duncan NA. Treatment adherence in hemophilia. Patient Prefer Adherence. 2017;11:16771686. doi:10.2147/PPA.S139851

10. Castaman G, Santoro C, Coppola A, et al. Emergency management in patients with haemophilia A and inhibitors on prophylaxis with emicizumab: AICE practical guidance in collaboration with SIBioC, SIMEU, SIMEUP, SIPMeL and SISET. Blood Transfus. 2020;18(2):143151. doi:10.2450/2019.0186-19

11. Rangarajan S, Walsh L, Lester W, et al. AAV5-factor VIII gene transfer in severe Hemophilia A. N Engl J Med. 2017;377(26):25192530. doi:10.1056/NEJMoa1708483

12. Pasi KJ, Rangarajan S, Mitchell N, et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for Hemophilia A. N Engl J Med. 2020;382(1):2940. doi:10.1056/NEJMoa1908490

13. George LA, Ragni MV, Samelson-Jones BJ, et al. Spk-8011: preliminary results from a phase 1/2 dose escalation trial of an investigational AAV-mediated gene therapy for hemophilia A. Blood. 2017;130(Suppl 1):604.

14. Pasi KJ, Laffan M, Rangarajan S, et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 2021;27(6):947956. doi:10.1111/hae.14391

15. Ozelo MC, Mahlangu J, Pasi KJ, et al. Valoctocogene roxaparvovec gene therapy for hemophilia A. N Engl J Med. 2022;386(11):10131025. doi:10.1056/NEJMoa2113708

16. Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):17271736. doi:10.1007/s11136-011-9903-x

17. OHara J, Martin AP, Nugent D, et al. Evidence of a disability paradox in patient-reported outcomes in haemophilia. Haemophilia. 2021;27(2):245252. doi:10.1111/hae.14278

18. OHara J, Hughes D, Camp C, Burke T, Carroll L, Diego DG. The cost of severe haemophilia in Europe: the CHESS study. Orphanet J Rare Dis. 2017;12(1):106. doi:10.1186/s13023-017-0660-y

19. Rentz A, Flood E, Altisent C, et al. Cross-cultural development and psychometric evaluation of a patient-reported health-related quality of life questionnaire for adults with haemophilia. Haemophilia. 2008;14(5):10231034. doi:10.1111/j.1365-2516.2008.01812.x

20. Wharfe G, Buchner-Daley L, Gibson T, et al. The Jamaican Haemophilia registry: describing the burden of disease. Haemophilia. 2018;24(4):e179e186. doi:10.1111/hae.13517

21. Sun HL, McIntosh KA, Squire SJ, et al. Patient powered prophylaxis: a 12-month study of individualized prophylaxis in adults with severe haemophilia A. Haemophilia. 2017;23(6):877883. doi:10.1111/hae.13319

22. Manco-Johnson MJ, Lundin B, Funk S, et al. Effect of late prophylaxis in hemophilia on joint status: a randomized trial. J Thromb Haemost. 2017;15(11):21152124. doi:10.1111/jth.13811

23. Limperg P, Terwee C, Young N, et al. Healthrelated quality of life questionnaires in individuals with haemophilia: a systematic review of their measurement properties. Haemophilia. 2017;23(4):497510. doi:10.1111/hae.13197

24. Bullinger M, Gardner DL, Lewis HB, et al. The potential impact of gene therapy on health-related quality of life (HRQoL) domains in haemophilia. J Haemophilia Pract. 2021;8(1):5668. doi:10.17225/jhp00176

25. Streiner D, Norman G. Health Measurement Scales: A Practical Guide to Their Development and Use. 2nd ed. Oxford University Press; 1995.

26. Kind P, Hardman G, Macran S. UK population norms for EQ-5D. Discussion Paper 172. The University of York Centre for Health Economics; 1999.

27. Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003;41(5):582592. doi:10.1097/01.MLR.0000062554.74615.4C

28. Kaplan RM. The minimally clinically important difference in generic utility-based measures. COPD. 2005;2(1):9197. doi:10.1081/copd-200052090

29. US Department of Health and Human Services FDA Center for Drug Evaluation and Research, US Department of Health and Human Services FDA Center for Biologics Evaluation and Research, US Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes. 2006;4:120. doi:10.1186/1477-7525-4-1

30. Valluri S, Flood E, Mink D, Bell J, Pocoski J, Sasane R. Determination of the minimal important difference (mid) of the hemophilia-specific quality of life questionnaire (Hemo-QOL-A) for adults with severe hemophilia A: PO-TU-233. Haemophilia. 2012;18(Suppl. 3):180181.

31. Gandhi M, Tan RS, Ng R, et al. Comparison of health state values derived from patients and individuals from the general population. Qual Life Res. 2017;26(12):33533363. doi:10.1007/s11136-017-1683-5

32. Peeters Y, Stiggelbout AM. Health state valuations of patients and the general public analytically compared: a meta-analytical comparison of patient and population health state utilities. Value Health. 2010;13(2):306309. doi:10.1111/j.1524-4733.2009.00610.x

See the article here:
Psychometric validation of the Haemo-QOL-A | PROM - Dove Medical Press

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Renovacor, Inc. (NYSE: RCOR), a biotechnology company focused on delivering innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases, today announced it has expanded its pipeline to advance an AAV gene therapy program as a potential precision therapy for three genetic segments of arrhythmogenic cardiomyopathy (ACM). To accelerate this new program, Renovacor has entered into a research collaboration with the University of Utahs Nora Eccles Harrison Cardiovascular Research and Training Institute (CVRTI). The terms of the research agreement grant Renovacor an option for an exclusive license to inventions generated from the collaboration.

The research collaboration will focus on a protein discovered by University of Utah scientists that has the potential to address multiple genetic segments of ACM. The new program is being developed as an AAV-based gene therapy to treat potentially life-threatening arrhythmias associated with the disease by restoring gap junction protein trafficking and gap junction communication between heart muscle cells. The program will be developed for the three largest genetic segments of ACM: plakophilin-2 (PKP2), desmoglein-2 (DSG2), and desmoplakin (DSP) associated ACM. Currently available treatment options do not address the trafficking defects central to each of the these genetically-driven forms of ACM.

The collaboration leverages positive proof-of-concept data generated in a genetic mouse model of ACM that was performed by the Shaw Lab, led by Robin Shaw, M.D., Ph.D., Professor of Medicine at the University of Utah and Director of the CVRTI. These data demonstrate restoration of gap junction trafficking to the intercalated disc and a significant reduction in premature ventricular contractions (PVCs). PVCs are a hallmark of ACM and key drivers of potentially lethal ventricular arrhythmias.

Renovacors pipeline expansion with this new AAV gene therapy research program for multiple genetic segments of ACM further demonstrates our precision medicine approach to develop potentially transformative therapies that target core biological drivers of serious cardiovascular diseases, said Matt Killeen, Ph.D., Chief Scientific Officer of Renovacor. We believe we have found the ideal program and partner to leverage our expertise in heart muscle biology to discover and develop a novel gene therapy that could one day address a significant unmet medical need.

We are thrilled to have Renovacor as a partner to continue the research into these very important genetic drivers of ACM, said Robin Shaw, M.D., Ph.D., Director of the CVRTI. ACM is a serious disease of heart muscle that can lead to life-threatening, intractable arrhythmias. The team at Renovacor are experts in the understanding the importance of heart muscle biology, which makes them the ideal development partner to advance a novel, precision medicine approach for ACM. By seeking to understand and address a key causal disease pathway in ACM, together we hope to develop a therapeutic that could help improve the lives of patients who are living with this serious form of cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a heritable heart muscle disorder that can affect the left and right ventricle. It is characterized by a heightened risk of potentially lethal ventricular arrhythmias, fibrofatty replacement of myocardial tissue, and in some patients, heart failure.(1,2) It is recognized as a disease of the desmosome, with well-defined genetic drivers. The prevalence of ACM is estimated to range from 1 case in 1,000 persons to 1 case in 5,000, with an average age of diagnosis of approximately 30 years.(1-3) Current treatment options aim to prevent potentially life-threatening arrhythmias and progression to end-stage disease, but they do not target the underlying genetics or disease biology and, as such, patients can continue to experience serious breakthrough events.(1-2)

About Renovacor

Renovacor is a biotechnology company focused on delivering innovative precision therapies to improve the lives of patients and families battling genetically-driven cardiovascular and mechanistically-related diseases. The companys lead program in BAG3-associated dilated cardiomyopathy (DCM) uses gene transfer technology to address the monogenic cause of this severe form of heart failure. Renovacors vision is to bring life-changing therapies to patients living with serious genetic cardiovascular and related diseases, by developing medicines that target the underlying cause of disease and provide a transformative benefit and significant improvement to quality of life.

About the University of Utah

The University of Utah is the states flagship institution of higher education, with 18 schools and colleges, more than 100 undergraduate and 90 graduate degree programs, and an enrollment of more than 32,000 students. The University serves as a catalyst for the regional innovation economy, having supported the launch and growth of over 300 companies and conducted more than $640 million in annual research.

---------------------

Austin KM et al Nat Rev Cardiol. 2019 Sep; 16(9): 519537

Corrado D, et. al, N Engl J Med 2017;376:61-72

McNally E (2017) in: Adam MP, Mirzaa GM, Pagon RA, GeneReviews

Forward-Looking Statements

This press release contains certain forward-looking statements within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995, as amended, including statements regarding the anticipated development of Renovacors product candidates and development programs. These forward-looking statements generally are identified by the words believe, project, expect, anticipate, estimate, intend, strategy, future, opportunity, plan, may, should, will, would, will be, will continue, will likely result, and similar expressions. These forward-looking statements are based upon current estimates and assumptions of the Company and its management and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release. Factors that may cause actual results to differ materially from current expectations include, but are not limited to: competition, the ability of the company to grow and manage growth, maintain relationships with customers and suppliers and retain its management and key employees; the Company's ability to successfully advance its current and future product candidates through development activities, preclinical studies and clinical trials and costs related thereto; the timing, scope and likelihood of regulatory filings and approvals, including final regulatory approval of our product candidates; changes in applicable laws or regulations; the possibility that the Company may be adversely affected by other economic, business or competitive factors; the Companys estimates of expenses and profitability; the evolution of the markets in which the Company competes; the ability of the Company to implement its strategic initiatives and continue to innovate its existing products; the ability of the Company to defend its intellectual property; the impact of the COVID-19 pandemic on the Companys business, supply chain and labor force; and the risks and uncertainties described in the Risk Factors section of the Company's annual and quarterly and reports filed the Securities Exchange Commission. These filings identify and address important risks and uncertainties that could cause actual events and results to differ materially from those contained in the forward-looking statements. Forward-looking statements speak only as of the date they are made. Readers are cautioned not to put undue reliance on forward-looking statements, and Renovacor assumes no obligation and does not intend to update or revise these forward-looking statements, whether as a result of new information, future events, or otherwise. Renovacor gives no assurance that it will achieve its expectations.

See the original post here:
Renovacor Announces Pipeline Expansion with New Research Program for Multiple Genetic Segments of Arrhythmogenic Cardiomyopathy - Business Wire

CAMBRIDGE, Mass., July 18, 2022 (GLOBE NEWSWIRE) -- Ring Therapeutics, a life sciences company founded by Flagship Pioneering to revolutionize gene therapy with its commensal virome platform, today announced three upcoming presentations at the 41st Annual Meeting of the American Society for Virology to be held from July 16-20, 2022 in Madison, Wisconsin. These presentations showcase Rings significant progress building out the Anellogy platform to engineer novel precision medicines through harnessing the unique biology of anelloviruses.

Oral Presentations:

Title: In vitro production of recombinant human anellovirus particles using synthetic viral genomesSession Title: Replication and Gene ExpressionAbstract Number: 3733463Board number: W49-10Presenter: Dr. Dhananjay NawandarPresentation Date and Time: Tuesday, July 19, 2022, 4:15 - 4:30 p.m. CST

This talk will present data from a study demonstrating an in vitro system to effectively produce anelloviruses and recapitulate tissue specific delivery in vivo. These results amplify basic understanding of anelloviruses and offer new insights into harnessing their unique biology for development of novel precision medicines.

Title: The First Structure of an Anellovirus Particle Reveals a Mechanism for Immune EvasionSession Title: W41: StructureAbstract Number: 3733650Presenter: Dr. Kurt SwansonPresentation Date and Time: Monday, July 18, 2022, 7:30 7:45 p.m. CST

This talk will showcase the first high resolution structure of an anellovirus and regions of the genome that are required for capsid assembly. The structure also provides a potential mechanism for anellovirus immune evasion, a hallmark of this viral family that could make them an ideal viral-based therapy.

Poster Presentations:

Title:Comprehensive profiling of antibody responses to anelloviruses within the commensal human virome using programmable phage display Session Title: Oncolytics, Gene Therapy and Viral VectorsAbstract Number: 3731105Board number: P28-1Presenter: Dr. Harish SwaminathanPresentation Date and Time: Monday, July 18, 2022, 8:30 - 10:00 p.m. CST

Data from this poster will illustrate that most anellovirus peptides are not associated with an antibody response in humans when compared to other known human viruses. These results further the understanding of anellovirus immune favorability.

About Ring TherapeuticsRing Therapeutics is revolutionizing the gene therapy and nucleic acid medicine space by harnessing the most abundant and diverse member of the human commensal virome, anelloviruses. The company developed the Anellogy platform which focuses on anelloviruses to potentially treat a broad range of diseases. Through harnessing the unique properties of these commensal viruses, the Anellogy platform generates diverse vectors that exhibit both tissue-specific tropism and the potential to be re-dosed. Ring Therapeutics, founded by Flagship Pioneering in 2017, aims to develop and further expand its portfolio by leveraging its platform to unlock the full potential of gene therapy and nucleic acid medicines, enabling a variety of mechanisms that successfully deliver therapeutic cargo to unreachable organs and tissues. To learn more, visit https://www.ringtx.com/ or follow us on Twitter at @Ring_tx.

Ring Therapeutics Media:Brittany Leigh, Ph.D.LifeSci Communicationsbleigh@lifescicomms.com+1-813-767-7801

Link:
Ring Therapeutics Announces Three Presentations at the 41st Annual Meeting of the American Society for Virology (ASV) - GlobeNewswire

Dive Brief:

Despite significant setbacks that have left the fate of its eye gene therapy in doubt and shares trading near all-time lows, Adverum hasnt given up.

The company is one of a few gene therapy makers aiming to develop a one-time treatment for diabetic macular edema and age-related macular degeneration, two common forms of vision loss that are treated with chronic injections of biologic medicines. But those drugs, like Eylea and Lucentis, are highly effective and considered safe, making the bar much higher for a gene therapy whose main goal is to improve convenience.

Adverums program was also beset by side effects the company once described as not seen before in ocular gene therapy, a combination of inflammation, vision loss and decrease in eye pressure observed in five trial participants.

Adverum stopped that trial, in diabetic macular edema, in 2021. At the time, some analysts suggested the company should attempt a reverse merger, a way for struggling biotechs to bring in new assets by combining with a privately held company seeking fast access to the public markets.

The company instead vowed to press on. Executives suggested testing a lower dose than previously planned with a different regimen of protective drugs could lead to better results in AMD. In 2021, the company noted that no cases of severe inflammation were observed in DME patients treated with a lower dose or in participants with AMD in another trial.

Adverum has since gained clearance from U.S. regulators for its new plan, a Phase 2 trial in AMD thatll test both the lowest dose evaluated in previous studies as well as one more than three-times lower. With shares trading at just over $1 apiece and equity harder to raise during the sectors downturn, Adverum has turned to cost-cutting to save money and fund the work. The savings could enable the company to get to one-year results from that trial, in 2023, without needing to raise more cash, wrote RBC analyst Luca Issi.

Yet Adverums odds remain long. A rival gene therapy from Regenxbio is already in Phase 3 testing in AMD, and pending positive results, could lead to an approval filing in 2024. The company remains a show-me story given its history, Issi wrote. Additionally, Adverums decision to turn to layoffs, rather than a partnership, may also signal limited strategic interest in the platform, he added.

Read more:
Adverum cuts jobs, restructures to give eye gene therapy another shot - BioPharma Dive

Jonah Sacha, Ph.D., at OHSU's Oregon National Primate Research Center and Vaccine & Gene Therapy Institute. (OHSU/Kristyna Wentz-Graff)

A new pre-clinical study in nonhuman primates will evaluate an experimental drugs potential use as a gene therapy that could prevent people who have HIV from having to take daily antiviral drugs for the rest of their lives.

The research will be led by Oregon Health & Science University researcher Jonah Sacha, Ph.D., who also serves as a scientific adviser to CytoDyn, the biotechnology company developing the drug, called leronlimab. The study is funded by a five-year grantof up to $5 million that was recently awarded to OHSU by the National Institute of Allergy and Infectious Disease, which is part of the National Institutes of Health.

This grant will fund the development and early study of leronlimab as a potential single-injection gene therapy, said Sacha, professor at OHSUs Vaccine and Gene Therapy Institute and Oregon National Primate Research Center. If this approach works as hoped, it could provide a functional cure for HIV, meaning it could suppress HIV enough that patients would no longer need to take daily antiviral pills for the rest of their lives."

In an earlier study, Sacha and colleagues found leronlimab completely preventednonhuman primates from being infected with the monkey form of HIV. That result indicated leronlimab held promise as a potential pre-exposure drug to prevent human infection from the virus that causes AIDS.

Now, this study aims to design a way to offer leronlimab as gene therapy. Sacha and colleagues will explore how to contain the coding sequence of the experimental drug inside a lab-made form of the adeno-associated virus, an approach that gene therapy researchers call an AAV vector. The resulting therapy would then be injected inside the body where muscle cells would make leronlimab long term.

Leronlimab is a monoclonal antibody that blocks HIV from entering immune cells through a surface protein called CCR5. The drug has demonstrated it can mimic a CCR5-deficient donor by occupying all available CCR5 molecules, but this would require a new method for delivery as a gene therapy. Viral vectors have been used to deliver antigens from specific pathogens for decades.

In this project, researchers will design a synthetic AAV vector to enable the long-term production leronlimab inside the body. The goal is to develop a safe and effective single injection that suppresses HIV replication and eliminates the need for life-long antiretroviral therapy.

Currently, patients often take multiple antiretroviral pills daily, said Sacha. Removing this pill burden could not only improve patients quality of life, but remove problems with adherence.

Rhesus macaques at OHSUs Oregon National Primate Research Center that have been exposed to a monkey version of HIV will be given a single AAV injection that contains leronlimab. Researchers will monitor the nonhuman primates for years to assess the safety and efficacy of this approach.

This research is supported by the National Institute of Allergy And Infectious Diseases of the National Institutes of Health under Award Number R01AI166969. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

In our interest of ensuring the integrity of our research and as part of our commitment to public transparency, OHSU actively regulates, tracks and manages relationships that our researchers may hold with entities outside of OHSU. In regard to this research, Dr. Sacha has a significant financial interest in CytoDyn, a company that may have a commercial interest in the results of this research and technology. Reviewdetails of OHSU's conflict of interest programto find out more about how we manage these business relationships.

All research involving animal subjects at OHSU must be reviewed and approved by the universitys Institutional Animal Care and Use Committee (IACUC). The IACUCs priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. No live animal work may be conducted at OHSU without IACUC approval.

Follow this link:
One-time gene therapy injection could provide HIV treatment that may last a lifetime - OHSU News

Emily Kaiser [EK]: Hello, welcome. I'm Emily Kaiser, editor of Modern Retina. I'm sitting down with Dr. Rahul Khurana to discuss the Aaviate study. Dr. Khurana, can you tell us a little bit about the Aaviate data presented at the Angiogenesis meeting?

Rahul Khurana, MD [RK]: For sure, Emily.

Aaviate is a really exciting clinical trial that I've been involved with and at Angiogenesis this year, we presented the updated data on the first two cohorts. And so to give everyone kind of a background, obviously, gene therapy is a very exciting area of interest right now.

We know there's a lot of unmet needs in our treatments of macular degeneration. You know, these treatments often are very effective, but they require a lot of treatments. And there's a high burden with our current set of treatments out there, and gene therapy offers the potential for a one-time treatment to give us long-term, anti-VEGF suppression and really a long-term answer to this kind of chronic disease.

And so Aaviate is along with many gene therapy programs, or studies, that are looking to kind of tackle this. And the thing which is interesting about Aaviate is that most of gene therapy has really looked at it the traditional approaches. Either theyve gone intravitreal, which is something we're very used to because we do these injections, or done a subretinal gene therapy delivery, which requires surgery, which is much more invasive. And Aaviate utilizes a suprachoroidal approach.

And the benefit of this is that we get good drug delivery of inhibiting anti-VEGF gene therapy, but by delivering it in the office. And one of the benefits of suprachoroidal delivery over intravitreal delivery is that in intravitreal, there is a potential for a lot of exposure of the medicine to not just the back of the eye, but also the front of the eye. And we've seen in some early gene therapy programs, a lot of complications involving inflammation and hypotony.

In a suprachoroidal approach, you can get a very high concentration to the retina with very low concentration to the anterior segment.

EK: That's really interesting. Has anything developed since the presentation?

RK: the study has been ongoing. So what I presented at Angiogenesis was the first two cohorts in the sense that those patients had been fully enrolled, and we had up to date up to six months. So that was really exciting. And we'll kind of delve into some of the details there. But there's still cohorts three, four, and five, which are now fully enrolled. So since that time, we've now fully enrolled those patients. And we're basically waiting to hear back on updates, or we were waiting to hear back those results. And we need to once they're fully enrolled, we need to have the subsequent time to see how these patients do.

EK: And what are the next steps?

RK: Part of the next steps for gene therapy is really to finish up the clinical study. The patients are all enrolled, which is wonderful. Now we want to see how they did in these higher enrolling cohorts. So one thing that we haven't talked about is what were the results that we actually found from the first two cohorts? And so as I mentioned before, Aaviate takes patients who have been previously treated so these patients who were in the study were basically patients who needed to get multiple injections.

On average, they average nearly nine injections in the previous year, which is about an injection every five weeks. And we took those patients who basically needed regular anti-VEGF therapy, and we basically offered them a super coronal injection of RGX-314, which involves a novel Aaviate vector, which encodes for an anti VEGF monoclonal antibody fragment, which is transduced, or basically transvexed, the patient's own retinal cells to produce anti-VEGF protein to effectively give you long term suppression.

And the data showed that in the first two cohorts where this was done, not only was the treatment quite safe, there was a very low rate of inflammation and no serious adverse events. But more impressively, that the number of treatments had gone down dramatically. The patients in the study were able to maintain their visual acuity, which was wonderful to see. But more importantly, the number of injections went down significantly.

As I told you, before, most of these patients needed about an injection every five weeks, and in the study, the number of injections went down nearly 70 to 79% than they had before receiving the gene therapy, they were able to maintain the visual acuity, maintain the retinal anatomy, and the number of patients who didn't even need injections was nearly 30% in the first cohort, and nearly 40% in the second cohort. And that was quite exciting because this truly was kind of delivering on the promise of a once-and-done therapy. But as I said before, we really need the long-term data to kind of see how this translates and also we need to see how higher doses if we can get better efficacy and also maintain a very good safety profile.

EK: Wow. So what does this mean for clinicians and for patients?

RK: I think it offers a really exciting hope for both our patients and physicians. As we mentioned before, we have a lot of treatment options for anti-VEGF therapy and they do work very well. The problem is that they require a lot of treatments and there's a high treatment burden, and this is challenging for patients because not all patients can come back in there's a high rate of lost to followup, non-compliance, and non-adherence to the treatment regimens. And we've seen in Phase 3 clinical studies, especially in follow up in real world practice that when patients are not getting regular treatments, they lose vision. And that's why we've it's been hard to replicate the excellent results we've seen in the Phase 3 studies in real world practice. And the hope is that if one of these gene therapy treatments can work, we can offer a really one-and-done or a much more sustainable treatment therapy for our patients, which ultimately lead to better compliance and better visual outcomes.

EK: Fantastic. Well, thank you so much for the update.

RK: My pleasure. Thanks for having me.

Note: This transcript has been lightly edited for clarity.

Original post:
AAVIATE: Gene therapy via suprachoroidal drug delivery may lower treatment burden for patients with AMD - Modern Retina