Category Archives: Gene therapy

WASHINGTON--(BUSINESS WIRE)--FerGene, a new gene therapy company formed by Ferring Pharmaceuticals and Blackstone Life Sciences, announced today positive results from the pivotal Phase 3 clinical trial evaluating nadofaragene firadenovec (rAd-IFN/Syn3), an investigational gene therapy, for the treatment of high-grade, Bacillus Calmette-Gurin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). FKD Therapies Oy (FKD) has led the development and regulatory filing of nadofaragene firadenovec, which has been studied in 33 centers across the U.S. in collaboration with the Society of Urologic Oncology Clinical Trials Consortium (SUO-CTC). The results were presented during the bladder cancer session at the Society of Urologic Oncology 20th Annual Meeting in Washington D.C.

The Phase 3 study of 157 patients from the U.S. met its primary endpoint with 53% of CIS Ta/T1 patients (carcinoma in situ; bladder cancer that is confined to the superficial layer, with or without concomitant high-grade Ta or T1 papillary disease) achieving a CR at three months, and 24% continuing to show a CR at 12 months. Moreover, the study also demonstrated broad efficacy in this difficult to treat patient population with a 73% HGRF survival in patients with papillary disease at three months and 44% HGRF survival at 12 months. In the study, nadofaragene firadenovec was instilled directly into the patients bladder every three months. All responses at 12 months were confirmed by protocol-mandatory five-point biopsies.

Bladder cancer is one of the most frequently occurring cancers with an estimated 699,450 people living with bladder cancer and more than 80,000 new cases diagnosed each year in the U.S. alone.1 In high-grade NMIBC patients, BCG is the standard treatment, and, although effective, over 60% of these tumors eventually re-occur. 2,3

Currently, patients living with high-grade NMIBC who are unresponsive to BCG have few treatment options and often face bleak outcomes, including complete bladder removal, known as cystectomy, said Colin P. N. Dinney, MD, Professor and Chairman of the Department of Urology at The University of Texas M.D. Anderson Cancer Center. Cystectomy is a complex and life-altering surgical procedure for patients, so these positive results from the Phase 3 trial of nadofaragene firadenovec are highly promising for patients. It would be gratifying to provide an alternative that addresses the critical unmet need for effective second-line therapy for patients facing radical cystectomy.

Efficacy Analysis*

AssessmentPeriod

CIS Ta/T1 Disease (n=103) CR(% [n])

High-Grade Ta/T1 Papillary Disease (non CIS)

(n=48) HGRF Survival (% [n])

Month 3

53.4% (55)

72.9% (35)

Month 6

40.8% (42)

62.5% (30)

Month 9

35.0% (36)

58.3% (28)

Month 12

24.3% (25)

43.8% (21)

*151 patients

In the Phase 3 trial, the most common adverse events (AEs) included fatigue, bladder spasm and discharge around the catheter, micturition urgency, hematuria, chills, fever, headache, painful urination, urinary tract infection, and diarrhea. No grade 4 or 5 treatment-related AEs were reported in the study. Study drug-related AEs were transient and local in nature, with a median duration of less than two days, with the exception of fatigue, which had a median duration of 11 days and urinary frequency which had a median duration of 41 days. There was a 1.9% percent rate of discontinuations due to study drug-related AEs.

We are pleased with these Phase 3 data results, including the complete response rates and favorable safety profile seen with nadofaragene firadenovec, said Nigel R. Parker4, PhD, of FKD Therapies Oy. These data were part of our submission package to the FDA, and we look forward to continuing to work with the agency to potentially bring nadofaragene firadenovec to patients with BCG unresponsive disease.

As a practicing urologist and trial investigator, its encouraging to see these types of efficacy and safety results in patients with high-grade NMIBC, an area thats been in need of new innovative treatment options for more than 20 years, said Neal Shore, MD, FACS, Medical Director, Carolina Urologic Research Center. These robust clinical results further demonstrate the potential of nadofaragene firadenovec as a valuable treatment option for NMIBC patients.

The U.S. Food and Drug Administration (FDA) has validated FKDs Biologics License Application (BLA) and granted Priority Review for nadofaragene firadenovec, which previously received Fast Track and Breakthrough Therapy Designations.

About nadofaragene firadenovec

Nadofaragene firadenovec (rAd-IFN/Syn3) is an investigational gene therapy being developed as a treatment for patients with high-grade, BCG unresponsive, NMIBC. It is an adenovirus vector-based gene therapy containing the gene interferon alfa-2b, administered by catheter into the bladder every three months. The vector enters the cells of the bladder wall, where, it breaks down, releasing the active gene to do its work. The internal gene/DNA machinery of the cells picks up the gene and translates its DNA sequence, resulting in the cells secreting high quantities of interferon alfa-2b protein, a naturally occurring protein the body uses to fight cancer. This novel gene therapy approach thereby turns the patient's own bladder wall cells into multiple interferon microfactories, enhancing the body's natural defenses against the cancer.

About Non-Muscle Invasive Bladder Cancer (NMIBC)

NMIBC is an early form of bladder cancer which is present in the superficial layer of the bladder and has not invaded deeper into the bladder or spread to other parts of the body.5 It is estimated that there will be 80,000 new cases of bladder cancer in the U.S. in 2019; more than 70% of these cases present as NMIBC.2,6 In patients with high-grade NMIBC, intravesical BCG is the recommended treatment; however, between 30% and 50% cases with high-grade disease will recur.7 The outcome for BCG unresponsive patients is poor, with total cystectomy (complete removal of the bladder) often being the next treatment option.8

About FerGene

FerGene, a new gene therapy company and Ferring subsidiary, has been created to potentially commercialize nadofaragene firadenovec in the U.S. and to advance the global clinical development. FerGenes goal is to bring this promising therapy to a patient population which has seen little improvement in their standard of care over the past twenty years. Blackstone Life Sciences will invest $400 million USD and Ferring will invest up to $170 million USD in FerGene. Ferring will also potentially launch and commercialize nadofaragene firadenovec outside of the U.S.

About FKD Therapies Oy

FKD Therapies Oy is a specialist gene therapy company based in Kuopio, Finland originally conceived by scientific and medical founders, Dr Nigel R Parker and Professor Seppo Yla-Herttuala4, for the specific purpose of undertaking the development of adenovirus mediated interferon alfa-2b. FKD has led the overall development of nadofaragene firadenovec through manufacturing at FinVector Oy, late stage clinical trials and the current BLA filing. FinVector Oy and FKD Oy are part of the Trizell Group.

About Ferring Pharmaceuticals

Ferring Pharmaceuticals is a research-driven, specialty biopharmaceutical group committed to helping people around the world build families and live better lives. Headquartered in Saint-Prex, Switzerland, Ferring is a leader in reproductive medicine and maternal health, and in specialty areas within gastroenterology and urology. Founded in 1950, Ferring now employs approximately 6,500 people worldwide, has its own operating subsidiaries in nearly 60 countries and markets its products in 110 countries.

1 National Cancer Institute. Cancer Stat Facts: Bladder Cancer. Available at: https://seer.cancer.gov/statfacts/html/urinb.html. Last accessed: December 2019.

2 Maruf, M et al., Non invasive bladder cancer: a primer on immunotherapy. Cancer Biol Med. 2016;13(2):194-205.

3 Derr, L et al., Intravesical Bacillus Calmette Guerin Combined with a Cancer Vaccine Increases Local T-Cell Responses in Non-muscle-Invasive Bladder Cancer Patients. Clin Cancer Res. 2017;23(3):717-725.

4 AIV Institute for Molecular Sciences, Kuopio, Finland.

5 Anastasiadis A, de Reijke TM. Best practice in the Treatment of Nonmuscle Invasive Bladder Cancer. Ther Adv Urol. 2012;4(1):13-32

6 Ghatalia, Pooja et al. Approved checkpoint inhibitors in bladder cancer: which drug should be used when?. Therapeutic advances in medical oncology vol. 10 1758835918788310. 30 Jul. 2018, doi:10.1177/1758835918788310.

7 Cambier S et al. EORTC Nomograms and Risk Groups for Predicting Recurrence, Progression, and Disease-specific and Overall Survival in NonMuscle-invasive Stage TaT1 Urothelial Bladder Cancer Patients Treated with 13 Years of Maintenance Bacillus Calmette-Gurin. European Urolology. 2016, Vol. 69(1): 60-69.

8 Cookson, M et al.,Use of intravesical valrubicin in clinical practice for treatment of nonmuscle-invasive bladder cancer, including carcinoma in situ of the bladder. Therapeutic Advances in Urology. 2014, Vol. 5(5):181-191.

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FerGene Announces Pivotal Phase 3 Study of Nadofaragene Firadenovec Met Its Primary Endpoint With More Than Half of Patients With High-Grade...

Gene therapy is an emerging field and industry is yet to work out how best to manufacture these life-saving products says expert. Interest in gene therapy is growing, says Andrew Powaleny, public affairs director at the Pharmaceutical Research and Manufacturers of America (PhRMA).

As of December 2018, the last time we did our analysis, there were 289 cell and gene therapies in development either in clinical trials or awaiting FDA approval, he adds.

And the interest is understandable. Gene therapies let doctors treat the root causes of disease, potentially curing patients. Also judging by products like Zynteglo and Zolgensma, which cost $1.7m and $2.1m, respectively, gene therapies will generate significant revenue for firms able to commercialize them successfully.

But manufacturing a gene therapy remains a complex technical challenge. Just ask Zynteglo developer, Bluebird Bio.

Zynteglo is designed to treat patients with transfusion-dependent -thalassemia (TDT). Development has not always been smooth. For example, in 2017 Bluebird announced it had made manufacturing process improvements for Zynteglo after the product disappointed in an earlier trial. However, in June this year it appeared Bluebird had turned things around when the EMA granted Zynteglo conditional clearance. But, in the approval presentation Bluebird announced it would not be able to launch the product until 2020.

Bluebird explained the delay was to allow it to work with the EMA to finalize commercial drug product specifications and manufacturing parameters. The situation changed again last month. The EMA accepted refined commercial drug product manufacturing specifications for Zynteglo. And Bluebird now expects the therapy to launch this year.

Similarly, Novartis, owner of the spinal muscular atrophy therapy Zolgensma, has encountered manufacturing issues. In October the firm said the EMA and Japans PMDA had extended their assessments of Zolgensma and asked for more CMC information.

Bluebird and Novartis travails are the high-profile examples, but the wider gene therapy sector faces manufacturing challenges according to Ashleigh Wake, laboratory director, Intertek Pharma Services Manchester.

Given the newness of medicines of this type there is limited historic information available on which to build strategy and as such adds extra uncertainty to any regulatory submission, says Wake. When considering how to build an effective CMC for a gene therapy IND, selection of critical assays will depend on the specific product but may include assays for concentration, purity such as determination of residual cellular DNA or empty viral particles, identity, activity, potency and stability.

Understanding which tests are critical to determining product quality is a key part of winning approval, continues Wake. From a regulatory perspective, an understanding of the critical quality attributes (CQAs) which impact product safety, purity, and potency are required. For gene therapy products this means developing and validating analytical assays to assess, vector productivity, vector purity, biological activity and safety.

With this in mind Intertek recently announced plans to expand its service center in Manchester in the UK.

Our expansion in laboratory footprint and recruitment of specialists in gene therapy analytics coupled with our integrated approach to analytical method lifecycle will mean we can develop methods which are best suited for the intended use at the various clinical stages on the way to commercialization, he points out.

The challenges will keep coming, according to Wake. She says therapies that use viral vectors will increase demand for quality control expertise and analytical technology.The inherent complexity of viral vector-based products makes physical and biological characterization highly challenging, she explains, citing the ability to differentiate between full capsids and empty ones as an example. In order to provide a complete quality control package, a range of analytical methods and technology are required, which incorporate instrumentation such as cryoelectron microscopy, qPCR or DDPCR which are not commonly associated with pharmaceutical quality control, in addition to techniques such as HPLC or analytical ultracentrifugation.

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Gene Therapy Production and Quality Control - Genetic Engineering & Biotechnology News

Tokyo-based FUJIFILM will invest 13 billion yen (about $120 million) to expand the companys gene therapy business and establish anew Gene Therapy Innovation Center adjacent to its current facility in College Station, Texas and add about 100 jobs.

The investment will include the addition of dedicated gene therapy laboratories and will be part of the existing FUJIFILM Diosynth Biotechnologies (FDB) in Texas, which opened last year. That site has been the companys center for excellence in gene therapy since 2014. The company is expanding its contract and development services for gene therapies as the market for CDMOs in gene therapy is expected to increase to $1.7 billion by 2025, the company said in its announcement.

The Gene Therapy Innovation Center, supported by a $55 million investment, will be approximately 60,000 square feet and will house state-of-the-art upstream, downstream and analytical development technologies. The facility is expected to be operational in the fall of 2021. Gene Therapy remains a strategic investment area for FUJIFILM.

Gerry Farrell, COO at FUJIFILM Diosynth Biotechnologies in Texas, said they anticipate breaking ground on the new facility in the first quarter of 2020. The new Texas sit will triple the companys gene therapy development capabilities and will add approximately 100 jobs to its Texas campus, Farrell said.

Martin Meeson, president and chief operating officer of the U.S. division of FUJIFILM Diosynth Biotechnologies, said the investment will allow FUJIFILM to support the incredible growth that the gene therapy sector has experienced over the past few years.

We know that we need to invest now, in technology, assets and people in order to achieve a market leadership position. The expansion through the construction of the Gene Therapy Innovation Center demonstrates our ongoing commitment for growth, Meeson said in a statement.

FUJIFILMs main goal behind its new strategy is to position itself as a key provider of leading, future-proofed end-to-end gene therapy solutions, from pre-clinical to commercial launch. For the company, this investment builds on earlier plans to introduce its gene therapy fill finish services.

For FUJIFILM, this investment in Texas comes several months after it snapped up Biogens biologics manufacturing operations in Denmark. FUJIFILM paid the Cambridge, Mass.-based company $890 million for the site that had about 800 employees. The acquisition is part of the companys expanded manufacturing strategy. Last year, the company acquired two biotechnology units from JXTG Holdings Inc. for about $800 million.

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FUJIFILM Expands Texas Holdings with New Gene Therapy Center - BioSpace

The Food and Drug Administration has halted a clinical trial involving a Duchenne muscular dystrophy gene therapy from Solid Biosciences (SLDB) after a patient suffered serious kidney and blood-related injuries, the company said Tuesday.

This is the third time that the Cambridge, Mass.-based Solid has run into a serious safety problem with its gene therapy, called SGT-001. The FDA placed similar clinical holds on the same clinical trial after each prior incident, but later allowed the company to proceed with patient dosing.

SGT-001 uses an inactivated virus to deliver a miniaturized but functional version of the dystrophin gene to muscle cells. The gene therapy is designed to be a one-time and potentially curative treatment for all Duchenne patients, regardless of the mutation that causes their disease.

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Sarepta Therapeutics (SRPT) and Pfizer (PFE) are also developing their own gene therapies targeted at Duchenne.

Six patients have been dosed with SGT-001, starting with three at a lower dose; interim results in those patients were previously reported and found to be disappointing. Three more patients were then treated at a higher dose of SGT-001.

The sixth patient became ill soon after being treated in October, experiencing an over-activation of the immune system, an acute kidney injury, reductions in platelets and red blood cells, and cardio-pulmonary insufficiency, Solid said.

All of the toxicities were deemed related to SGT-001 by the patients treating doctor. The patient is being treated and is recovering, Solid said.

Solid reported the patients status to the FDA, which then placed the clinical trial on hold. In a statement, the company said it will work with the FDA in an effort to resolve the hold and determine next steps for the clinical trial.

Pfizers Duchenne gene therapy has also been tied to similar immune system over-activation and related kidney toxicity, although its clinical trial remains active.

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Solid's Duchenne gene therapy trial halted after patient suffers toxicity - STAT

COLLEGE STATION, Texas, Nov. 14, 2019 /PRNewswire/ -- FUJIFILM Diosynth Biotechnologies (FDB), a leading global biologics Contract Development and Manufacturing Organization (CDMO) has announced the expansion of its gene therapy services with the addition of dedicated process and analytical development laboratories. As a part of a capital investment of approximately 13 billion yen (approx. $120 million USD) in the gene therapy fieldby FUJIFILM Corporation,aninvestment of approximately $55 million USD will be made to establish anew Gene Therapy Innovation Center adjacent to FDB's existing state-of-the-art cGMP gene therapy manufacturing facility in College Station, Texas and forms part of the company's strategy to meet the growing demands in the Viral Gene Therapy Market. The gene therapy market forecast for CDMOs is expected to grow to $1.7Bn by 2025.1

The Gene Therapy Innovation Center will be approximately 60,000 square feet and will house state-of-the-art upstream, downstream and analytical development technologies. The facility will be operational in the fall of 2021.

"We are very much aware of the incredible growth in such an important therapeutic space," said Martin Meeson, President and COO of FUJIFILM Diosynth Biotechnologies, US. "We know that we need to invest now, in technology, assets and people in order to achieve a market leadership position. The expansion through the construction of the Gene Therapy Innovation Center demonstrates our ongoing commitment for growth."

FDB's main goals behind this new strategy are to provide leading, future proofed end-to-end gene therapy solutions, from pre-clinical to commercial launch. This follows an earlier announcement made by FDB to introduce its gene therapy fill finish services. "We expect to break ground in the first quarter of 2020," said Gerry Farrell, COO at FUJIFILM Diosynth Biotechnologies, Texas, "this new facility will triple our gene therapy development capabilities and will add approximately 100 jobs to our Texas Campus."

Gene Therapy remains a strategic investment area for Fujifilm.

About Fujifilm FUJIFILM Diosynth Biotechnologies an industry-leading Biologics Contract Development and Manufacturing Organization (CDMO) with locations in Teesside, UK, RTP, North Carolina, College Station, Texas and Hillerod, Denmark. FUJIFILM Diosynth Biotechnologies has over thirty years of experience in the development and manufacturing of recombinant proteins, vaccines, monoclonal antibodies, among other large molecules, viral products and medical countermeasures expressed in a wide array of microbial, mammalian, and host/virus systems. The company offers a comprehensive list of services from cell line development using its proprietary pAVEway microbial and Apollo cell line systems to process development, analytical development, clinical and FDA-approved commercial manufacturing. FUJIFILM Diosynth Biotechnologies is a partnership between FUJIFILM Corporation and Mitsubishi Corporation. For more information, go to: http://www.fujifilmdiosynth.com

FUJIFILM Holdings Corporation, Tokyo, Japan, brings cutting edge solutions to a broad range of global industries by leveraging its depth of knowledge and fundamental technologies developed in its relentless pursuit of innovation. Its proprietary core technologies contribute to the various fields including healthcare, graphic systems, highly functional materials, optical devices, digital imaging and document products. These products and services are based on its extensive portfolio of chemical, mechanical, optical, electronic and imaging technologies. For the year ended March 31, 2019, the company had global revenues of $22 billion, at an exchange rate of 111 yen to the dollar. Fujifilm is committed to responsible environmental stewardship and good corporate citizenship. For more information, please visit: http://www.fujifilmholdings.com.

All product and company names herein may be trademarks of their registered owners.

1 Market research conducted by FUJIFILM Diosynth Biotechnologies strategic business development group.

SOURCE FUJIFILM Diosynth Biotechnologies

Global CDMO

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FUJIFILM Diosynth Biotechnologies Announces $55 Million USD Investment To Expand Gene Therapy Development Capabilities - PRNewswire

This years American Academy of Ophthalmology meeting in San Francisco had significant data releases from pharmaceutical companies focused on the treatment of neovascular age-related macular degeneration with gene therapy.

Regenxbio announced data about its lead compound RGX-314 delivered via subretinal delivery. The study tested five different doses in 42 patients previously treated with anti-VEGF agents. Overall, the subretinal delivery was well tolerated without significant intraocular inflammation. There was a dose-dependent increase of the protein in aqueous samples across the five arms. The data presented showed six patients with 1.5 years of follow-up and an impressive +9 letter visual gain from baseline. Three of the six patients were injection-free at 18 months, and the number of patients who were injection-free increased with the amount of protein delivered in cohort 4 and 5.

So, is gene therapy ready for prime time? While the data are very encouraging, the procedure is still invasive and requires surgery rather than a simple intravitreal injection, so its not likely to be the entry-level treatment. Will retina specialists commit all patients to the therapy if a small minority of patients do not require more than two to three injections over 2 years? That still remains to be determined. Lastly, with the advent of different mechanisms of action like pan-VEGF agents and anti-angiopoietin 2 agents, this will likely be step therapy for those patients with persistent or recurrent disease.

Nonetheless, there are really promising results on a platform that appears to be safe and effective in the management of active neovascular AMD.

Like what you are reading? Follow me on Instagram, Facebook and Twitter @drrishisingh.

Disclosure: Singh reports he is a consultant to Zeiss, Novartis, Regeneron, Genentech and Alcon and receives grant support from Apellis and Graybug.

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BLOG: Gene therapy promising for treatment of neovascular AMD - Healio

CHICAGO, Nov. 13, 2019 /PRNewswire/ -- According to Arizton's recent research report, Cell and Gene Therapy Market - Global Outlook and Forecast 2019-2024 is expected to grow at a CAGR of more than 24% during the forecast period.

Key Highlights Offered in the Report:

Key Offerings:

Get your free sample today! https://www.arizton.com/market-reports/cell-and-gene-therapy-market

Cell and Gene Therapy Market Segmentation

Market Segmentation by Products

Market Segmentation by Distribution Channel Type

Market Segmentation by End-users

Cell and Gene Therapy Market Dynamics

CAR T-cell therapy has gained significant traction in recent years. It is the single most rapidly growing type of product in the market that generates revenue at a phenomenal rate. At present, it is the fastest advancing technology in cancer treatment and has the capability to replace many existing therapies. CAR T-cell therapy addresses current challenges in cancer care through superior efficacy, safety, and delivery mechanisms. CAR T-cell therapy has brought itself into focus due to the personalized nature of this therapy and the utilization of advanced genetic engineering technology. The wide acceptance and use of CAR T-cell therapy is fueling the growth of the global cell and gene therapy market.

Key Drivers and Trends fueling Market Growth:

Cell and Gene Therapy MarketGeography

The US dominates the cell and gene therapy market in North America due to the high prevalence of chronic diseases and other conditions. There is also comparably high utilization and wide accessibility of these therapies. In Europe, cell and gene therapy products are considered to be part of the Advanced Therapy Medicinal Products (ATMPs), which are commonly known as regenerative medicine globally. The major factors leading to the growth in APAC region are the growing prevalence of cancers, osteoarthritis, burns, and other chronic wounds, the introduction of advanced products in Japan, advanced R&D activities in countries such as South Korea, India.

Get your free sample today! https://www.arizton.com/market-reports/cell-and-gene-therapy-market

Market Segmentation by Geography

Major Vendors

Other vendors include - Anterogen, Tego Sciences, Japan Tissue Engineering, JCR Pharmaceuticals, Medipost, MolMed, AVITA Medical, CollPlant, Corestem, Biosolution, Stempeutics Research, Orchard Therapeutics, Takeda Pharmaceutical Company, CHIESI Farmaceutici, CO.DON, AnGes, GC Pharma, JW CreaGene, APAC Biotech, Nipro Corp., Terumo, Orthocell, and bluebird bio.

Explore our healthcare & lifesciencesto know more about the industry.

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About Arizton:

Arizton Advisory and Intelligence is an innovation and quality-driven firm, which offers cutting-edge research solutions to clients across the world. We excel in providing comprehensive market intelligence reports and advisory and consulting services.

We offer comprehensive market research reports on industries such as consumer goods & retail technology, automotive and mobility, smart tech, healthcare, and life sciences, industrial machinery, chemicals and materials, IT and media, logistics and packaging. These reports contain detailed industry analysis, market size, share, growth drivers, and trend forecasts.

Arizton comprises a team of exuberant and well-experienced analysts who have mastered in generating incisive reports. Our specialist analysts possess exemplary skills in market research. We train our team in advanced research practices, techniques, and ethics to outperform in fabricating impregnable research reports.

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The Cell and Gene Therapy Market to Reach Revenues of Over $6.6 billion by 2024 - Market Research by Arizton - PRNewswire

Dive Brief:

The companies identified Rett, Angelman and Dravet syndromes and Niemann-Pick disorder as the first four conditions that the new collaboration will try to treat. Four more could emerge, which would trigger an additional $42.5 million in additional payments.

Sarepta is paying the initial $48 million upfront fee in the form of combined cash and shares. StrideBio will be eligible for additional undisclosed development, regulatory and sales milestones, as well as royalties. The privately-held partner also will have an option to co-commercialization rights to one of the gene therapies, if successful.

The four StrideBio agents will join a Sarepta pipeline that already has 23 identified projects in clinical or pre-clinical development.

Cambridge, Massaschusetts-based Sarepta stated the collaboration will utilize StrideBio's "unique approach" to engineering capsids, the shells surrounding the adeno-associated virus (AAV) used by many researchers to deliver genes to cells.

StrideBio's technology tries to better target which cells their AAV-based therapies reach, as well as avoid triggering neutralizing antibodies, which can reduce the effectiveness of a gene therapy.

Immune responses to some AAV-based therapies have raised safety concerns. On Tuesday, Solid Biosciences announced the Food and Drug Administration had put a hold on its AAV9-based gene therapy for Duchenne muscular dystrophy (DMD) because of immune responses, although Sarepta's own DMD gene therapy has not seen anything similar.

As part of the agreement, Sarepta and StrideBio "plan to focus on strategies intended to address re-dosing challenges in patients who have received AAV-delivered gene therapy."

Re-treatment of patients who don't respond or have unlimited response to gene therapies is an unanswered question in this quickly evolving field, and drug developers and payers alike will closely watch any developments that emerge from the Sarepta-StrideBio re-dosing work.

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Sarepta brings in more gene therapies with StrideBio deal - BioPharma Dive

American Gene Technologies in Rockville, Maryland says it has submitted an application to the FDA for a gene therapy it claims eliminates HIV.

CBS Baltimore reports: The company said the therapy, AGT103-T, is a genetically-modified product made from a persons own cells that focuses on repairing damage to the immune system caused by HIV. The company expects to start a phase one clinical trial in humans in January.

Said Chief Science OfficerC.David Pauza, PhD: Our aim is to treat HIV disease with an innovative cell and gene therapy that reconstitutes immunity to HIV and will control virus growth in the absence of antiretroviral drugs. Development of this complex product (AGT103-T) required our deep knowledge of both HIV disease and lentivirus vector technology; it is the first cell and gene immunotherapy addressing the most critical feature of HIV infection, which is the chronic absence of virus-specific CD4 T cells.

SaidJeff Galvin, Founder and Chief Executive Officer of AGT: We are excited to have reached this milestone of submitting our first IND application to the FDA for an HIV gene/cell therapy. This event brings us closer to reaching our mission to transform lives with genetic medicines. Based on our successful commercial-scale product manufacturing runs and features of the product observed in our laboratories, this therapy has a high potential to be effective. I feel confident thatAGT103-Twill make an important difference in the lives of HIV infected persons. HIV is the first drug candidate to result from AGTs proprietary platform and model for creating gene and cell therapeutics more efficiently, predictably and reliably for clinical development.

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Maryland Company Claims to Have Cure for HIV/AIDS Through Gene Therapy, Expects Clinical Trial in January: WATCH - Towleroad

Heart failure (HF) is the most frequent cardiovascular diagnosis and exacts significant health and financial costs around the globe. It is estimated that at least 26 million people worldwide are living with HF, including nearly 6 million in the United States.1, 2 One in nine U.S. deaths in 2009 included heart failure as a contributing cause and about 50 percent of people in the U.S. with HF die within five years of diagnosis.2 The annual cost of HF-related healthcare services, medication and missed days of work is estimated at $40 billion in the United States and $108 billion globally.3, 4 Quality of life in HF patients is frequently worse than many other chronic diseases and comorbidities are common.5-7 The challenges of HF are expected to grow, as it is estimated that more than 8 million people in the United States alone will have HF by 2030.2 Current therapies improve quality of life in the short-term and have improved long-term survival but a significant number of patients have Class 3 HF despite optimal medical and device therapy. These patients have limited treatment options beyond heart transplant and left ventricular assist devices (LVAD). New therapeutic approaches that address the underlying causes of HF are needed to improve patient outcomes.

Heart failure is a complex disease process and multiple pathways contribute to its development and progression. Myocardial ischemia is frequently an issue in both ischemic and non-ischemic cardiomyopathy as well as HF with preserved and/or reduced ejection fraction. Myocardial ischemia results in insufficient oxygen and nutrients and leads to hypoxia, cardiomyocyte and fibrosis, which all contribute to the progression of heart failure. More effective angiogenesis may prevent this progression. Cell homing also plays a critical role, as injured cardiac tissue secretes factors that lead to the recruitment, proliferation, migration and differentiation of progenitor cells that can help repair tissue damage. Stromal cell-derived factor (SDF)-1 has been shown to play an important role in cardiac repair by mediating cell homing.10 Mitochondrial energy generation is also impaired in HF, leading to decreased contractility and adverse changes to cardiac architecture.11 Scar tissue formed in response to cardiomyocyte injury or death can compromise the hearts mechanical strength or electrical signaling results in myocardial infarction. Inflammatory responses to cardiac tissue damage can promote inappropriate and chronic inflammation and the expression of pro-inflammatory molecules that lead to pathologic changes to cardiac architecture.12, 13

These pathways offer a variety of potential new targets for therapeutic intervention to prevent the development and progression of HF. This opens the door to the development of novel therapies that address the underlying molecular and cellular causes of disease rather than treating HF symptoms alone.

After decades of development, gene-based therapies are now validated therapeutic modalities for the treatment of inherited retinal disorders and cancer and are undergoing clinical evaluation in a variety of inherited, acute and chronic diseases. Nearly two dozen single gene-based therapies for HF have been evaluated in clinical trials.14 Genes evaluated as monogenic gene therapy for HF in clinical trials include vascular endothelial growth factor (VEGF) and fibroblast growth factor type 4 (FGF4) to promote angiogenesis; adenylyl cyclase type 6 (AC6) and sarco/endoplasmic reticulum Ca2+-ATPase type 2 (SERCA2) to improve cardiac calcium homeostasis, which plays a critical role in the contraction and relaxation of heart muscle; and stromal cell-derived factor-1 (SDF-1) to improve cell homing and promote cardiac tissue repair. Late-stage trials of single gene therapies have yielded conflicting results, raising the question as to whether positively impacting a single pathway can be sufficient to overcome detrimental activity of other pathways that contribute to the development and progression of HF. Other potential limitations to HF therapies evaluated in clinical trials to date include the method of delivery, dose and the potency of vectors and gene products.

Given the multiple molecular and cellular pathways active in HF, a multi-gene approach to HF gene therapy may be needed. Simultaneously delivering multiple genes that target diverse HF-related pathways has the potential to improve cardiac biology and function. A triple gene therapy approach (INXN-4001, Triple-Gene LLC, a majority-owned subsidiary of Intrexon Corporation) is currently in clinical development, with each of the genes targeting a specific HF-related pathway. The investigational drug candidate INXN4001 vector expresses: the S100A1 gene product, which regulates calcium-controlled networks and modulates contractility, excitability, maintenance of cellular metabolism and survival; SDF-1a which recruits stem cells, inhibits apoptosis and supports new blood vessel formation; and VEGF-165 which initiates new vessel formation, endothelial cell migration/activation, stem cell recruitment and tissue regeneration. The hypothesis is that the simultaneous delivery of multiple genes in a single vector would more effectively improve multiple aspects of cardiac function compared with single gene therapy. It is delivered by retrograde coronary sinus infusion of a triple effector plasmid designed with a self-cleaving linker to constitutively express human S100A1, SDF-1a and VEGF 165. This route is designed to allow for delivery of a dose to the ventricle which may help achieve improved therapeutic effect.

Several preclinical studies have set the foundation on which to advance a triple gene therapy for HF into the clinic.15-17 Using in vitro studies, transfecting cells derived from patients with dilated cardiomyopathy with a triple gene combination demonstrated improvement in contraction rate and duration, to the levels demonstrated by the control cells and did not result in increased cell death compared to controls.15 Studies in an Adriamycin-induced cardiomyopathy rodent model demonstrated triple gene therapy increased fractional shortening and myocardial wall thickness compared to controls.16 In addition, retrograde coronary sinus infusion of INXN-4001 in a porcine model of ischemic HF resulted in a cardiac-specific biodistribution profile.17

A Phase 1 clinical study has been initiated to evaluate the safety of a single dose of triple gene therapy in stable patients implanted with a LVAD for mechanical support of end-stage HF. An independent Data and Safety Monitoring Board agreed to proceeding to the second cohort following review of the data from the first cohort in the multi-site study.18 The study is ongoing and final results will help to inform our understanding of the potential that multi-gene therapy may play in the treatment of HF.

The recent FDA approvals of gene therapies for an inherited retinal disease and cancer are evidence that gene therapy is a valid therapeutic strategy. Realizing the potential of gene therapy in HF will require appropriately designed clinical trials, but several interesting approaches currently in development may prove to be effective. The results of the initial investigational drug INXN-4001 Phase 1 trial should provide insight into the safety of combining S100A1, SDF-1a and VEGF-165. Evaluation of additional multi-gene combinations will also be important for understanding which targeted pathways yield the greatest effects with respect to relevant clinical endpoints. Continued refinement and optimization of vector design and delivery methods will also be important for advancing further HF gene therapies from bench to bedside.

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The Heart of the Matter: Leveraging Advances in Cardiac Biology to Innovate Gene-Based Therapies for Heart Failure - Physician's Weekly