Category Archives: Gene therapy

On 19 November, the UK BioBeat19 summit goes to Stevenage to discuss the potential of cell and gene therapy and how to accelerate these transformational medicines.

Victoria Higgins of GSK and Miranda Weston-Smith from BioBeat spoke to two panellists who gave a sneak peek of their remarks and agree wholeheartedly that the discovery side and clinical side work best when they are teamed up.

Sophie Papa, an oncologist at Guys Cancer at Guys and St Thomas NHS Trust, and Aisha Hasan, a clinical development lead at GSK, both recognise the big challenge ahead for cell therapy researchers: to dial up efficacy and dial down toxicity.

Cell and gene therapies, with their remarkable potential to transform medicine, have seen some important but hard-won milestones: it took 20 years of combined academic and industry research to deliver the first gene therapy approval in 2016 and today there are two CAR-Ts approved for haematological malignancies.

Whilst CAR-Ts recognise proteins expressed on the tumour cell surface, making them ideal for targeting blood cancers, more complicated but with greater potential to address solid tumours are the gene modified TCR-T technologies.

These harness the power of T cells to specifically target and destroy tumours even on the inside of cells. TCR-Ts come with an additional level of complexity, but potentially open the door to a range of untreatable cancer types.

Looking at the TCR opportunity is where Sophie Papa sees the inherent trade-off between risk and benefit as an academic clinician whos now evaluating modified T-cell based therapies in clinical trials.

Sophie urges her peers to take courage. It is important to be brave and tolerant of certain toxicities. Academic clinicians and drug researchers need to work closely together to engage the regulators in early discussion, so that we can move cell therapies earlier in treatment schedules as soon as feasible.

Timing is critical to enable patients to be treated when they are physically fit so they can better tolerate these complex and potentially toxic treatments.

From her perspective, this is not an either/or, but an area where discussion and open dialogue will allow us to make the most of the opportunity. By allowing clinical academics to play a lead role in developing guidelines to manage patient safety, we can address legitimate concerns but not let them stand in the way of clinical development, she says.

Aisha brings the perspective of drug discovery and development and starts by asking what is in the realm of the possible from a design perspective.

She says: A superior T-cell therapy will require engineering approaches that enhance efficacy on one-end while also incorporating switches to minimise toxicity.

For example, in a counter-intuitive way, a T-cell with high-killing capacity actually can create dangerous levels of inflammation in the body, due to the rapid death of cancer cells. But the beauty of drug design opens up options:By building a switch within the engineered T-cells, researchers can inactivate the T-cells and prevent harm to the patient, says Aisha.

But this creative problem solving requires open dialogue between clinicians and pharma. Aisha says: The more we talk about clinical need and toxicity benchmarks, the more sophisticated we can be when developing the next generation of enhanced engineered cell therapies.

Theres no doubt that the challenges of delivering cell and gene therapy span the full spectrum of issues related to medicine development. However, the potential for both curative therapy and commercial opportunity is tremendous.

The scientific, clinical, technical, regulatory and commercial challenges are all surmountable when everyone in the ecosystem work together towards a shared goal, united by an unwavering focus on the patient.

Sophie and Aisha are speaking about the translational journey from science to bedside at the BioBeat19 summit.

The BioBeat19 summit on Accelerating cell and gene therapy, 1-6pm, Tuesday 19 November, GSK Stevenage. Guarantee your place by registering at http://www.biobeat19.org

Read the original:
Next generation cell and gene therapies: fine tuning the promise - Business Weekly

It's a very early report, from just two patients, only a few months after treatment. But UMass Medical School Dean Terence Flotte this week shared at a conference what could be landmark news about a terrible genetic disease: Two young patients with Tay-Sachs disease showed no ill effects from a new gene therapy that aims to correct the defect at the heart of the disease.

One of them, treated at just 7 months, has appeared to stabilize instead of following the typical quick slide toward death by age 4.

"It seems right now that she's not degenerating," Flotte said. "But I would say it's too early to say that definitively."

Tay-Sachs is a fatal disorder that tends to affect babies of Eastern-European Jewish ancestry, along with other ethnicities including Cajun and Irish. They usually seem to develop normally for the first few months, but as the disease kills off their nerve cells, they lose the ability to move or breathe on their own.

Flotte says the brain MRI of the baby treated at 7 months looks encouraging, and a clinical trial in more than a dozen patients is expected to begin soon.

Edited highlights of our conversation follow.

You've just presented at a gene therapy conference. What did you report?

We reported the first two patients ever treated with gene therapy for Tay-Sachs disease two infants treated at UMass Memorial Medical Center. What we presented was that these two patients were both treated safely. The vector[the engineered virus that delivered the genetic fix] was administered directly into the brain.

We saw bio-activity, which basically means that we partially restored the enzyme that is missing in Tay-Sachs disease. And the patients were able to tolerate that safely. Also, in one of the cases, with the patient treated early in the course of the disease, we've seen some stabilization of the patient's condition.

What do you mean by stabilization?

One of the patients was treated at 2-1/2 years of age, and that patient had really advanced disease. And we've seen the biochemical effect, but really no clinical effect.

The second patient was treated between 6 and 7 months of age, and in that patient, it appears, although it's still very early, that the patient may be having some continued preservation of her ability to sit up and control her muscles. She's basically seeming to have a more gradual progression at the current time, really being stable at a time point when we might be expecting her to lose some of these developmental milestones.

The best way to explain it is that if a normal infant begins to sit up at around six months of age, Tay-Sachs babies do that, but then they tend to lose the ability to sit up some time between 10 months of age and maybe 15 months of age. The last time we assessed the patient, at 10 months of age (and she's now close to 12 months of age), she seems to not be losing any of the strength required to sit up. We have her older siblings for comparison, and it's encouraging that she seems to be progressing less than they did. We also saw some encouraging signs on her brain MRI.

It seems right now that she's not degenerating. But I would say it's too early to say that definitively. If you think about the progression of development as the slope of a line, the line is flat at this point. It's not going up or going down. The next assessment will be very important, to see whether she's continuing to be flat, which would be a major benefit, or whether she's regressing but just a little bit more slowly.

When you say flat, she's also not advancing as a typical child would?

That is right. It looks like preservation of function rather than gaining. But her oldest sibling died before his third birthday. So considering how fast these patients can decline, a preservation or stabilization could be very important.

It's important to note, too, that we are just at the very beginning. The first patient got the vector injected just into the fluid around the brain, the cerebro-spinal fluid, not into the brain tissue. The second patient got a portion of it injected into the thalamus, which projects out to the entire brain tissue. It's kind of the relay center of the brain, and it can actually ship enzyme out all over the brain.

No one's ever tried that in a humans before, so that was really an important milestone, that intra-thalamic injection. As the trials progress, a larger dose will be injected into the thalamus.

Why has there never been an injection into the thalamus in humans before? What's the challenge?

One challenge is that it is a completely irreplaceable structure. Effectively, all motor and sensory function relays through the thalamus. So if you were to have bleeding or injury to the thalamus, it could cause a stroke or a persistent pain syndrome. So it is somewhat risky. On the other hand, when you're dealing with the infantile form of Tay-Sachs, it's so tragic that it warrants a rather risky approach.

It's been done many times in animals, but this was the first time doing it in patients.

What's next? A full clinical trial?

Yes, Axovant has licensed the program. This first program was done all at UMass Medical School and UMass Memorial Medical Center, and the program is now licensed to Axovant, and they are planning in the near future to do a Phase 2 trial, which we will still be involved in.

It will entail increasing the proportion of the vector injected into the thalamus, so that we will get to the exact proportional dose that was used to correct all of the different animal models that have been treated: a mouse, a sheep and a cat model.

UMassMed Magazine has more on the school's Tay-Sachs gene therapy work here.

Link:
Early Report: Baby Treated With Gene Therapy For Deadly Tay-Sachs Disease Appears To Stabilize - WBUR

The U.S. National Institutes of Health (NIH) wants to cure HIV and sickle cell disease with gene therapies, and will invest $100 million over the next four years towards that goal, the agency announced today (Oct. 23).

For this effort, the NIH will partner with The Bill & Melinda Gates Foundation, which will also invest $100 million.

Critically, the partnership aims to make the therapies affordable and accessible to people around the world, particularly in developing countries, where the burden of these diseases is greatest.

"This is a very bold goal, but we have decided to go big," Dr. Francis Collins, director of the NIH, said in a news conference today.

The effort aims to have the therapies ready for testing in clinical trials in the U.S. and sub-Saharan Africa within the next seven to 10 years.

Related: 10 Amazing Things Scientists Just Did with CRISPR

The majority of the 38 million people with HIV live in developing countries, with two-thirds living in Sub-Saharan Africa. For sickle cell disease, the majority of cases also occur in Sub-Saharan Africa.

The NIH has been trying to find a cure for HIV for "decades and decades," said Dr. Anthony Fauci, director of The National Institute of Allergy and Infectious Diseases. Although current treatments with antiretroviral therapy (ART) are effective at suppressing the virus in the body, they are not a cure, and must be taken everyday. What's more, there are millions of people with HIV who don't have access to ART treatment.

Although scientists are working to develop gene-based cures for HIV, these approaches are often costly and would be difficult to implement on a large scale, Fauci said. For example, some of these therapies take cells out of a patient's body and then re-infuse them, an expensive and time-consuming intervention.

For this reason, the new collaboration will focus on developing cures that use "in vivo" approaches, meaning they happen inside the body, Fauci said. One example of this could be to remove the gene for the CCR5 receptor, which HIV uses to get inside cells. Another idea is to excise the HIV "proviral" DNA that has copied itself into the human genome and lurks in the body even after years of treatment.

Similarly, for sickle cell disease, the goal would be to develop an in vivo therapy that could repair the genetic mutation that causes the disease. This would require a gene-based delivery system that could selectively target the mutation.

"Beating these diseases will take new thinking and long-term commitment. I'm very pleased to see the innovative collaboration announced today, which has a chance to help tackle two of Africa's greatest public health challenges," Matshidiso Rebecca Moeti, the World Health Organization's Regional Director for Africa, said in a statement.

Still, much work would be needed to make sure these therapies are safe and effective.

"It is very clear we have a ways to go, which is why this is a 10 year effort to try and take that promise and turn it into a reality," Collins said.

Earlier this year, the Trump Administration announced a plan to end the HIV epidemic in the U.S. in 10 years.

Originally published on Live Science.

See the article here:
Can Gene Therapy Cure HIV? US Gov't. Is Banking $100 Million On It. - Livescience.com

Dive Brief:

The EMA's green light for Bluebird's manufacturing removes a final hurdle standing in the way of marketing the gene therapy, which costs $1.8 million per patient.

A requirement from European authorities to narrow drug product specifications for Zynteglo forced the company to delay the gene therapy's launch later than when Wall Street analysts had expected.

In a statement, Apceth said it's ready for the challenge to bring Bluebird's treatment to market. Between 2,000 and 3,000 patients in the European Union would be eligible under the conditions approved by regulators for Zynteglo's use.

Bluebird has cautioned investors to take a long view of the new treatment's prospects, and to expect a slow start. In addition to winning approval for the new manufacturing specifications, Bluebird has to navigate through healthcare systems that aren't used to paying large sums for a one-time treatment.

In hopes to alleviating those problems, the company has offered an installment plan that would require later payments only if the treatment continues to benefit patients. The hope is that Zynteglo saves healthcare dollars by sparing beta-thalassemia patients the need for regular blood transfusions and the complications that can go along with them.

Patients with the blood disorder carry a genetic mutation that hinders the body from effectively producing the crucial oxygen-carrying protein hemoglobin. As a result, they often require transfusions every two to five weeks to fight anemia.

"This is one step along the commercial journey as we advance our ongoing launch and market access activities on a country-by-country basis," said Alison Finger, Bluebird's chief commercial officer, in the company's statement on the EMA's nod.

In a September company presentation, Bluebird said it wants to make sure to "get the model right" as it looks toward future gene therapies it's developing in its pipeline. The company is initially planning to offer Zynteglo through treatment centers in Germany, Italy, the U.K. and France, with a drug manufacturing facility in Munich.

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Bluebird gets European green light for gene therapy production - BioPharma Dive

Zolgensma, a lifesaving treatment for infants and the worlds most expensive drug, has been used to treat 100 patients since its launch and brought in $160 million for its maker Novartis (NVS) last quarter, beating analysts expectations.

The gene therapy is a treatment for spinal muscular atrophy, a rare and devastating neurological disease. It carries a record price tag of $2.1 million, or an annualized cost of $425,000 per year for five years.

Novartis said Tuesday that roughly 99% of SMA patients who qualified for Zolgensma got coverage of the one-time therapy, although some had to go through an approval process to receive the drug. The company also indicated that it made progress in striking deals with health plans to cover the drug, saying that agreements are in place covering roughly 90% of patients insured commercially and roughly 30% of patients covered by Medicaid.

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I think the overall uptake that were seeing very early in the launch speaks to the promise of the product, the physician excitement, and the parent and patient desire to get kids on gene therapy, said Dave Lennon, president of AveXis, Novartiss gene therapy business.

The strong sales numbers came over a summer that saw a controversy involving manipulation of data used to support Zolgensmas approval by the Food and Drug Administration. In an unusual rebuke, the agency said in August that AveXis knew that preclinical data had been falsified before the drug was approved in May, but did not inform the Food and Drug Administration until later. The agency said that the drug should stay on the market, but the scandal sparked anger from lawmakers and a pledge from Novartiss CEO, Vas Narasimhan, to move more quickly on disclosing issues around data integrity.

Lennon said Novartis worked quickly to reassure patients and physicians of Zolgensmas quality, and the data manipulation scandal had no real impact on the treatments commercial performance, Lennon said.

Zolgensmas early success could be a worrying sign for Biogen, whose Spinraza has been the treatment of choice for SMA since its approval in 2016. More than 50% of patients treated with Zolgensma had switched over from Spinraza, according to Novartis, preferring a one-time therapy over Biogens every-four-months treatment.

Zolgensmas sales outstripped what analysts had forecasted. One average of analysts projections, from Bloomberg, had pegged the drugs sales for the quarter at $86 million. Another compiler of financial estimates, FOA, had gauged analysts consensus at $106 million.

Novartis expects revenue to grow. The company is counting on approvals for Zolgensma in Europe and Japan next year, and it recently presented data demonstrating the gene therapys effects on older SMA patients. Novartis is also counting on an expansion of newborn testing for SMA, which is currently done in 30% of U.S. states but could rise to 70% by 2020, according to the company.

Time is neurons for these kids, and we really want to make sure they get gene therapy as soon as possible, Lennon said.

Original post:
Novartis gene therapy brings in $160 million, beating expectations - STAT

Cobra Moradian, Fatemeh Rahbarizadeh

Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran

Correspondence: Fatemeh RahbarizadehDepartment of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal AleAhmad Highway, Tehran 14115-111, IranTel +98 21 82883884Fax +98 21 82884555Email rahbarif@modares.ac.ir

Background: Breast cancer stem cells (BCSCs) are cells with a higher ability to metastasis and resistance to conventional treatments. They have a phenotype of (CD44high/CD24low) and the unlimited ability for proliferation. Development of strategies to target the BCSC population may lead to the establishment of more effective cancer therapies. Pseudomonas exotoxin A (PE) is a potent cytotoxic protein. CXCR1 promoter provides BCSC and HER2 specificity on transcription level. 5UTR of the basic fibroblast growth factor-2 (bFGF 5UTR) provides tumor specificity on translation level. Here, we utilized a mutant form of PE encoding DNA PE38, CXCR1 promoter and bFGF 5UTR to target BCSCs.Methods: The stemness of SK-BR-3, MDA-MB-231 and MCF10A cell lines were evaluated based on the expression of the CD44high/CD24low stem cell signature and the ability to form mammospheres. Then, the cell lines were transfected with constructs encoding luciferase/PE38 under the control of the CMV/CXCR1 promoter with or without bFGF 5UTR. Luciferase protein expression was evaluated using dual-luciferase reporter assay. PE38 transcript expression was measured by real-time PCR, and the cytotoxic effect of PE38 protein expression was determined by MTT assay.Results: The percentage of CD44high/CD24low population did not correlate to mammosphere forming efficiency (MFE). Given that the percentage of CD44 high/CD24 low is not a conclusive BCSC profile, we based our work on the mammosphere assay. However, in comparison with MCF10A, the two tumorigenic cell lines had higher MFE, probably due to their higher BCSC content. Reporter assay and real-time PCR results demonstrated that CXCR1 promoter combined with bFGF 5UTR increased BCSC-specific gene expression. Meanwhile, tightly regulated expression of PE38 using these two gene regulatory elements resulted in high levels of cell death in the two tumorigenic cell lines while having little toxicity toward normal MCF10A.Conclusion: Our data show that PE38, CXCR1 promoter and bFGF 5UTR in combination can be considered as a promising tool for killer gene therapy of breast cancer.

Keywords: breast cancer stem cell, PE38, CXCR1 promoter, bFGF-2, HER2, mammosphere

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Targeted Toxin Gene Therapy Of Breast Cancer Stem Cells Using CXCR1 Pr | OTT - Dove Medical Press

During the third-quarter financial call, Vasant Narasimhan, CEO of Novartis, noted that questions from European and Japanese regulators regarding chemistry, manufacturing and controls (CMC) were behind expected decision dates on Zolgensma (onasemnogene abeparvovec) being pushed back into 2020.

At present, the company expects to receive opinions from the European Medicines Agency (EMA) and the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in the first quarter and the first half of 2020, respectively.

Narasimhan revealed few other details regarding the questions, only that there were an extensive set of questions with respect to manufacturing, to which it had submitted responses. Reuters stated that he also confirmed that the decision delay was not due to the revelation of data manipulation in August.

Despite the setback on potential approval date, the company was able to confirm that the product had achieved US sales of $160m (143m), arriving higher than analyst predictions of $98m (88m).

When questioned on the patient numbers this related to, on paid programs, Narasimhan confirmed that approximately 100 patients had been treated though other patients had received the gene therapy through treatment in clinical trials.

Once approved in elsewhere in the world, Narasimhan predicted such number could increase rapidly: I think in some countries in Europe, as well in the Middle East, there could be very strong demand coming very quickly after approval.

He cited pent-up demand as a reason that sales would increase quickly, and also pointed to early access programs being made available in France, Portugal and Germany as another positive long-term sign for the product.

The company will need to see substantial return on the product, after investing $8.7bn in the AveXis acquisition to gain access to the technology.

See the original post here:
Novartis gene therapy held up by manufacturing questions - BioPharma-Reporter.com

Some gene therapies, such as bluebird bios Zynteglo, work by modifying a patients own blood stem cells to deliver a functioning gene. While they hold great potential as life-saving treatments for many immune system disorders and blood-based conditions, the process for administration can be costly and time-consuming.

In a study published in the journal Blood, scientists at Scripps Researchdescribed a possible way to more efficiently deliver genes to improve gene therapy treatment outcomesand it involves a close relative to a natural compound found in grapes.

Take Zynteglo, formerly known as LentiGlobin. Approved in the EU to treat beta thalassemia, an inherited blood disorder, it uses a lentiviral vector to insert a functioning version of the beta-globin gene into a patients blood-producing hematopoietic stem cells (HSCs) outside of the body. When the cells are given back to the patient, the gene can multiply and start to make healthy red blood cells.

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However, HSCs protect themselves with structures known as interferon-induced transmembrane (IFITM) proteins against viral attacks. Therefore, in preparation for a gene therapy, the lentiviral vectors could be intercepted several timeswasting a large amount of expensive materialsbefore a successful delivery.

This is why gene therapy of hemopoietic stem cells has been hit-or-miss, Bruce Torbett, the studys senior author, said in a statement. We saw a way to potentially make the treatment process significantly more efficient.

Torbett and colleagues at Scripps Research focused on caraphenol A, a small molecule related to resveratrol, which is a natural compound produced by grapes widely known for its antioxidant and anti-inflammatory effects.

The team found that adding caraphenol A to human HSCs, along with lentiviral vectors, could reduce the cells natural defenses by lowering the levels of IFITM2 and IFITM3, allowing the vectors to pass more easily. The effect was even more pronounced once the HSCs were transplanted into mice, as the cells divided and produced blood cells with the corrected gene, according to the team.

RELATED:Improving viral vectors for hemophilia gene therapies by tricking the immune system

Because gene therapy holds the promise of a potential cure for debilitating diseases that are deadly or require long-term care, scientists have been exploring new ways to improve it. A research team at the San Raffaele Telethon Institute for Gene Therapy in Italy recently found integrating the protein CD47 in the surface of lentiviral vectors could help them escape detection and destruction by the immune system once inside the body.

Torbett and his team believe caraphenol A could reduce costs of HSC-based gene therapy, which are high: Bluebird has priced Zynteglo at 1.6 million ($1.8 million) in Europe. It could also save time by helping patients get the therapy sooner. And because the longer stem cells stay outside of the body, the more likely they are to lose their ability to self-generate, more efficient gene delivery could also preserve their self-renewing properties, Tobett said.

See more here:
Could a grape-based compound improve gene therapy efficiency? - FierceBiotech

Sanofi is playing catch-up in gene therapy, but new CEO Paul Hudson is taking quick steps to close the gap. A reorganization of the R&D unit is intended to pivot thedrugmaker toward immuno-oncology drugs and gene therapies. And to hasten the transition, the company is retrofitting a vaccine plant in France into a gene therapy manufacturing operation.

A spokesman Monday confirmed Sanofi is preparing teams at its Lyon-Gerland site to work on vector-based gene therapies. John Reed, Sanofi's head of R&D,spoke about the project in an interview with BioPharma Dive.The drugmaker expects the facility to be operational a year from now.

RELATED: Sanofi quits Voyager gene therapy deal once worth up to $845M

De-Risking the Solid Form Landscape of an API

This presentation will discuss how predictable stability and solubility can minimize development timelines and cost. Attend to hear about two case studies exemplifying the importance of understanding the hydration space of an API and how hydrate formation may be avoided by development of a robust crystallization procedure.

Sanofi has invested about 25 million in the Lyon-Gerland site over the last five years. In 2013, the drugmaker struck a deal with France's Transgene to share the cost of a 10 million facility thereto manufacture Transgene's immuno-oncology therapies.

The Lyon vaccine facility is being retrofitted even as Sanofi this summer reworked itsgene therapy partnership with Voyager Therapeutics. Sanofi dumped two programs it has started with Voyager, and now the two will develop adeno-associated virus capsids the protein shells of the virusfor the delivery of gene therapies. Sanofi gets the exclusive option to use these capsids to deliver treatments for up to two non-CNS diseases.

RELATED: Sanofi U.S. plant sets new bar for biologics production

The project also comes as Sanofi has been upgrading other parts of its manufacturing network for the future. Last week, it opened a new biologics plant in Massachusetts that it considers its prototype plant of the future. In the digitally enabled manufacturing facility, all manufacturing stages are controlled through analytical processes that are forecast to avoid variations.

Plant operators also have access to data analytics or augmented reality solutions that can help them make real-time decisions and adjustments. Sanofisaid the remade plant is 80 times more productive while also reducing energy use and emissions by 80%.

As for gene therapy production, Sanofi is following other companies such bluebird bio and Gileads Kite Pharma in building viral vector manufacturingfacilities to serve their gene therapy or CAR-T development programs, which are much further along than Sanofi's.

See original here:
Sanofi starts on viral vector facility as its R&D focus shifts to gene therapies - FiercePharma

SOUTH PLAINFIELD, N.J., Oct. 24, 2019 /PRNewswire/ --PTC Therapeutics, Inc., (NASDAQ: PTCT) today announced new results from its investigational gene therapy, PTC-AADC, in patients living with aromatic L-amino acid decarboxylase (AADC) deficiency. The datademonstrated clinically meaningful and sustained improvements in motor, cognitive and language milestones. These included the ability to sit, walk, and talk and represents up to five years of follow up post-treatment.1,2 PTC-AADC is a one-time gene therapy treatment of the human dopa decarboxylase (DDC) gene administered into the putamen, which supports production of key neurotransmitters. The data were presented at the Child Neurology Society 48th Annual Meeting.

"We are excited to see the transformational effects in AADC deficiency patients in this long-term study as patients with severe AADC deficiency never achieve the ability to sit, walk or talk," said Stuart Peltz, Ph.D., Chief Executive Officer of PTC Therapeutics. "We are on track to submit a BLA to the FDA by the end of the year and are proud to be on the verge of bringing the first commercial treatment for AADC deficiency patients which is in line with our mission of bringing clinically differentiated treatments to patients with rare disorders."

New analysis evaluated outcomes of 26 patients with AADC deficiency across three separate clinical trials,2 making it the most comprehensive analysis of patients treated with PTC-AADC to date. Specifically, these results showed that 12 months post-treatment with PTC-AADC, patients' mean body weight had increased from 12.0 kg to 15.2 kg, and the frequency of oculogyric crises (involuntary upward eye movement) was reduced.2 Dyskinesia (involuntary movements) was the most frequently recorded adverse event, however most events were mild or moderate and all cases resolved by 10 months post-treatment.2

"In addition to failing to reach key developmental milestones, such as walking and talking, children with AADC deficiency can experience severe symptoms that affect their everyday lives. These symptoms can include episodes of oculogyric crises, which can last for minutes or hours and involve sustained upward movement of the eyes, involuntary movements of the neck, tongue protrusions and jaw spasms, which can be very distressing for patients and their families," said Claudio Santos, M.D., Senior Vice President, Global Medical Affairs, PTC Therapeutics. "The post-treatment data presented at CNS confirm reductions in the number of patients experiencing oculogyric crises, suggesting that this gene therapy treatment has the potential to make a real difference in the lives of patients with AADC deficiency."

A separate analysis of a long-term study demonstrated the sustained efficacy of PTC-AADC up to five years.1 These are the longest data available for any investigational treatment for AADC deficiency. These results showed clinically meaningful and sustained improvements in motor, cognitive and language milestones up to five years post-treatment with PTC-AADC.1

An additional abstract building on the existing understanding of AADC deficiency was also presented, giving a disease state overview that highlights the potential importance of a gene therapy to treat this condition.3

About aromatic L-amino acid decarboxylase (AADC) deficiencyAromatic L-amino acid decarboxylase (AADC) deficiency is a rare genetic condition caused by a mutation in the dopa decarboxylase (DDC) gene, resulting in a lack of functioning AADC enzyme, which is responsible for the final step in the synthesis of key neurotransmitters dopamine and serotonin.4

AADC deficiency results in delays or failure to reach developmental milestones such as head control, sitting, standing, walking, or talking, low muscle tone (also known as muscular hypotonia), severe, seizure-like episodes involving involuntary eye movement (also known as oculogyric crises), autonomic abnormalities, and the need for life-long care.4 Given this neurologically devastating illness, patients with severe AADC deficiency have a high risk of death during childhood. There are currently no approved therapies that address the underlying cause.

About PTC Therapeutics, Inc.PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically-differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to globally commercialize products is the foundation that drives investment in a robust pipeline of transformative medicines and our mission to provide access to best-in-class treatments for patients who have an unmet medical need. To learn more about PTC, please visit us onwww.ptcbio.comand follow us onFacebook, on Twitter at @PTCBio, and on LinkedIn.

For More Information:

Investors:Emily Hill+ 1 (908) 912-9327ehill@ptcbio.com

Media: Jane Baj+1 (908) 912-9167jbaj@ptcbio.com

References:

Forward-LookingStatements:This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future expectations, plans and prospects for PTC; expectations with respect to PTC's gene therapy platform, including any potential regulatory submissions; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions.

PTC's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: expectations with respect to the potential financial impact or PTC's ability to realize the anticipated benefits of the acquisition of Agilis and its gene therapy platform, including with respect to the business of Agilis and expectations with respect to the potential achievement of development, regulatory and sales milestones and contingent payments to the former Agilis equityholders with respect thereto and PTC's ability to obtain marketing approval of PTC-AADC and other product candidates acquired from Agilis, will not be realized or will not be realized within the expected time period; significant transaction costs, unknown liabilities, the risk of litigation and/or regulatory actions related to the acquisition of its gene therapy pipeline, as well as other business effects, including the effects of industry, market, economic, political or regulatory conditions; the eligible patient base and commercial potential of PTC-AADC; and the factors discussed in the "Risk Factors" section of PTC's most recent Annual Report on Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urged to carefully consider all such factors.

As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including PTC-AADC.

The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this press release except as required by law.

View original content:http://www.prnewswire.com/news-releases/ptc-therapeutics-announces-results-from-long-term-aadc-deficiency-gene-therapy-treatment-demonstrating-sustained-improvements-300944629.html

SOURCE PTC Therapeutics, Inc.

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PTC Therapeutics Announces Results from Long-Term AADC Deficiency Gene Therapy Treatment Demonstrating Sustained Improvements - BioSpace