Etranacogene dezaparvovec

~ Alignment with FDA continues to support Accelerated Approval pathway ~ ~ BLA submission planned for first quarter of 2026 ~ ~ Conference call today at 8:30 a.m. ET ~ LEXINGTON, Mass. and AMSTERDAM, June 02, 2025 (GLOBE NEWSWIRE) -- uniQure N.V. (NASDAQ: QURE), a leading gene therapy company advancing transformative therapies for patients with severe medical needs, today provided a regulatory update on AMT-130, its investigational gene therapy for the treatment of Huntington’s disease. Following recent Type B meetings and further guidance from the U.S. Food and Drug Administration (FDA), the Company has reached alignment with the FDA on several key components of the statistical analysis plan and Chemistry, Manufacturing and Controls (CMC) information that will support a Biologics License Application (BLA) submission expected in the first quarter of 2026. “We are very pleased with our continued, productive engagement with the FDA and the progress we’ve made toward a planned BLA submission for AMT-130 in the first quarter of 2026,” said Walid Abi-Saab, M.D., chief medical officer of uniQure. “We are pursuing an accelerated approval pathway supported by multiple years of clinical data – a rigorous and differentiated approach that reflects the urgent need in Huntington’s disease and our commitment to delivering the first disease-modifying treatment for people affected by this devastating disease. We are grateful to the FDA for their continued engagement and look forward to sharing three-year top-line data in the third quarter of 2025.” Statistical Analysis Plan In the second quarter of 2025, the Company held a Type B meeting with the FDA to discuss the proposed use of external control data and the prospectively defined statistical analysis plan (SAP) in support of the planned BLA submission for AMT-130. The FDA continued to support its prior agreement that the composite Unified Huntington’s Disease Rating Scale (cUHDRS) may serve as an acceptable registrational, intermediate clinical endpoint for accelerated approval. The FDA agreed that the primary efficacy analysis for the BLA will evaluate the 3-year change in cUHDRS in high-dose AMT-130 patients compared to a propensity score-adjusted external control arm. The Company plans to use propensity score-weighted external control derived from the ENROLL-HD dataset for the primary analysis and to submit certain sensitivity analyses, including one using a propensity score-matched external control, as additional support. The FDA also agreed that ENROLL-HD – a large, prospective, longitudinal, natural history study of patients with Huntington’s disease – may be acceptable as the external control dataset for the primary analysis of the trial data along with additional sensitivity analyses using the TRACK-HD/TRACK-ON and PREDICT-HD datasets. To date, approximately 33,000 patients have enrolled in ENROLL-HD. Compared to previously used natural history studies like TRACK-HD and PREDICT-HD, ENROLL-HD offers a substantially larger sample size, lower attrition rates, and longer average patient follow-up. The Company expects the larger sample size to reduce variability in the external control data and enhance the robustness of the SAP. The Company plans to submit an updated SAP consistent with discussions from the recently held Type B meeting to the FDA in the second quarter of 2025. Chemistry, Manufacturing and Controls (CMC) In the first quarter of 2025, the Company held a Type B meeting with the FDA to discuss CMC requirements in support of the planned BLA submission for AMT-130. The FDA agreed that validation of the AMT-130 manufacturing process should be possible using experience and prior knowledge from the etranacogene dezaparvovec-drlb (HEMGENIX®) process, complemented with additional full-scale AMT-130 GMP batches and a single Process Performance Qualification (PPQ) batch. The FDA also agreed with the Company’s proposed drug product release testing plan, including the proposed potency assay, pending completion of qualification and specification setting activities. Next Steps for the Planned BLA Submission Based on these recent Type B meetings with the FDA, the Company continues to prepare for a BLA submission for AMT-130 in the treatment of Huntington’s disease. Certain key next steps and expected timing include: Q2 2025: submit updated SAP to the FDAQ3 2025: initiate PPQ run and present topline Phase I/II data per the SAPQ4 2025: hold pre-BLA meeting with the FDAQ1 2026: submit BLA with a request for priority review designation Investor Conference Call and Webcast Information uniQure management will host an investor conference call and webcast today, Monday, June 2, 2025 at 8:30 a.m. ET. The event will be webcast under the Events & Presentations section of uniQure’s website at https://www.uniqure.com/investors-media/events-presentations, and following the event a replay will be archived for 90 days. Interested parties participating by phone will need to register using this online form. After registering for dial-in details, all phone participants will receive an auto-generated e-mail containing a link to the dial-in number along with a personal PIN number to use to access the event by phone. If you are joining the conference call, please dial in 15 minutes before the start time. About the Phase I/II Clinical Program of AMT-130 uniQure is conducting two multi-center, dose-escalating, Phase I/II clinical studies to explore the safety, tolerability, and exploratory efficacy signals of AMT-130 for the treatment of Huntington’s disease. In the U.S. study, a total of 26 patients with early manifest Huntington’s disease were randomized to treatment (n=6 low dose; n=10 high dose) or an imitation (sham) surgical procedure (n=10). Treated patients received a single administration of AMT-130 through MRI-guided, convection-enhanced stereotactic neurosurgical delivery directly into the striatum (caudate and putamen). The study consists of a blinded 12-month core study period followed by unblinded long-term follow-up of treated patients for five years. An additional four control patients crossed over to treatment. The European open-label Phase Ib/II study of AMT-130 enrolled 13 patients with early manifest Huntington’s disease (n=6 low dose; n=7 high dose). A third cohort enrolled an additional 12 patients across sites in the U.S. and EU. This cohort was randomized to explore both doses of AMT-130 in combination with immunosuppression, using the current, established stereotactic administration procedure. Additional details are available on www.clinicaltrials.gov (NCT0543017, NCT04120493) AMT-130 has been granted the FDA’s Regenerative Medicine Advance Therapy (RMAT) designation and Breakthrough Therapy designation, the first therapy for Huntington’s disease to receive an RMAT designation. About Huntington’s Disease Huntington’s disease is a rare, inherited neurodegenerative disorder that leads to motor symptoms including chorea, behavioral abnormalities and cognitive decline resulting in progressive physical and mental deterioration. The disease is an autosomal dominant condition with a disease-causing CAG repeat expansion in the first exon of the huntingtin gene that leads to the production and aggregation of abnormal protein in the brain. According to 2021 study in Neuroepidemiology, approximately 70,000 people have been diagnosed with Huntington’s disease in the U.S. and Europe, with hundreds of thousands of others at risk of inheriting the disease. Despite the clear etiology of Huntington’s disease, there are currently no approved therapies to delay the onset or to slow the disease’s progression. About uniQure uniQure is delivering on the promise of gene therapy – single treatments with potentially curative results. The approvals of uniQure’s gene therapy for hemophilia B – an historic achievement based on more than a decade of research and clinical development – represent a major milestone in the field of genomic medicine and ushers in a new treatment approach for patients living with hemophilia. uniQure is now advancing a pipeline of proprietary gene therapies for the treatment of patients with Huntington's disease, refractory temporal lobe epilepsy, ALS, Fabry disease, and other severe diseases. www.uniQure.com uniQure Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical fact are forward-looking statements, which are often indicated by terms such as "anticipate," "believe," "could," “establish,” "estimate," "expect," "goal," "intend," "look forward to", "may," "plan," "potential," "predict," "project," “seek,” "should," "will," "would" and similar expressions and the negatives of those terms. Forward-looking statements are based on management's beliefs and assumptions and on information available to management as of the date of this press release. Examples of these forward-looking statements include, but are not limited to, statements concerning: the availability of accelerated approval pathways and the need for additional pre-approval studies for AMT-130; the Company’s anticipated timing of the BLA submission; the Company’s plans to submit a revised SAP and CMC information to the FDA; the Company’s ability to deliver a potentially life-changing therapy to people living with Huntington’s disease and related timeline for doing so; the potential clinical and functional effects of AMT-130; the Company’s plans to continue clinical development of AMT-130; the Company’s plans to share clinical data of AMT-130 in the third quarter of 2025; and the utility of the ENROLL-HD patient dataset with respect to Phase I/II study. The Company may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements. Furthermore, the Company’s actual results could differ materially from the plans, intentions and expectations anticipated in these forward-looking statements for many reasons. These risks and uncertainties include, among others: risks related to the Company’s Phase I/ll clinical trials of AMT-130, including the risk that interim data from the trials may not be predictive of later data readouts that will serve as a basis for further regulatory interactions, may not support BLA submissions or accelerated approvals, may not be satisfactory to the FDA and other regulators, and new analyses of existing data and results may produce different conclusions than established as of the date hereof; risks related to the Company’s current and future interactions with regulatory authorities, which may affect the initiation, timing and progress of clinical trials, its BLA submission plans and pathways to regulatory approval; risks related to the Company’s ability to pursue business development efforts with respect to AMT-130; risks related to the Company’s use of propensity-weighted external controls in connection with its statistical analysis of clinical outcomes to date; uncertainties as to the FDA’s and other regulatory authorities’ interpretation of the data from the Company’s Phase I/ll clinical trials of AMT-130 and acceptance of the Company’s clinical programs and the regulatory approval process; later developments with the FDA and other regulators that could be inconsistent with the feedback received to date; and whether regulatory authorities will accept the Company’s approach as a basis for accelerated approval; risks related to the Company’s use of nominal p values as a basis for its statistical analyses; whether the measurements that the Company is evaluating continue to be viewed as robust and sensitive measurements of disease progression; whether RMAT designation or any accelerated pathway, will lead to regulatory approval; the Company’s ability to continue to build and maintain the infrastructure and personnel needed to achieve its goals; the Company’s effectiveness in managing current and future clinical trials and regulatory processes; the Company’s ability to demonstrate the therapeutic benefits of its gene therapy candidates in clinical trials; the continued development and acceptance of gene therapies; the Company’s ability to obtain, maintain and protect its intellectual property; and the Company’s ability to fund its operations and to raise additional capital as needed and on acceptable terms. These risks and uncertainties are more fully described under the heading "Risk Factors" in the Company’s periodic filings with the U.S. Securities & Exchange Commission (SEC), including its Annual Report on Form 10-K filed with the SEC on February 27, 2025, its Quarterly Reports on Form 10-Q filed May 9, 2025, and in other filings that the Company makes with the SEC from time to time. Given these risks, uncertainties and other factors, you should not place undue reliance on these forward-looking statements and, except as required by law, the Company assumes no obligation to update these forward-looking statements, even if new information becomes available in the future. uniQure Contacts: FOR INVESTORS:FOR MEDIA: Chiara RussoTom MaloneDirect: 617-306-9137Mobile: 617-306-9137Mobile: 617-306-9137Mobile:339-223-8541c.russo@uniQure.comt.malone@uniQure.com

Besides tepid interest thanks to the availability of existing treatments, an infrastructure barrier has also been an obstacle to the uptake of CSL's hemophilia gene therapy Hemgenix. After Pfizer let limited patient interest get the best of its hemophilia B gene therapy ambitions and discontinued Beqvez, CSL Behring naturally faced the question of whether it can hold its ground with Hemgenix.Hemgenix’s own struggles became obvious to CSL about a year into its launch. As the first hemophilia gene therapy approved by the FDA in November 2022, Hemgenix only treated 12 patients during the 12 months that ended in June 2024.Despite the challenges, including what CSL CEO Paul McKenzie has described as a fragmented U.S. healthcare system, the blood product specialist remains hopeful that Hemgenix is here to stay.“I hope we always remain committed to [Hemgenix],” Bob Lojewski, general manager of North America at CSL Behring, said in an interview with Fierce Pharma.“The patient community has been supportive of CSL. They’ve been grateful for us to not do what Pfizer did,” he said. “And our intention is to make it more widely available and easier to get.” A small patient populationWhen Pfizer pulled Beqvez off the market in February, the Big Pharma company cited limited interest from patients and doctors toward hemophilia gene therapies in general.CSL has felt that pain, too.Hemophilia B is a rare blood disorder characterized by a deficiency of the clotting factor IX caused by a defect in the FIX gene. Hemgenix, like Beqvez, uses an adeno-associated virus (AAV) vector to deliver a functional copy of the FIX gene to achieve stable expression of the critical blood-clotting protein.Hemophilia B only accounts for about 15% to 20% of all hemophilia cases. It’s estimated that around 33,000 patients with hemophilia live in the U.S., according to the CDC.Not all hemophilia B patients are eligible for Hemgenix, Guy Young, M.D., director of the hemostasis and thrombosis center at Children’s Hospital Los Angeles, pointed out in an interview.The one-time gene therapy is only approved for adults. In addition, Young noted that payers are likely to limit the drug’s use to patients with severe or moderately severe disease, among whom Hemgenix was tested in a phase 3 trial. These patients typically have 2%—or lower—levels of factor IX compared to a roughly 50% level that’s considered normal. The list of Hemgenix’s restrictions goes on. Because it comes with a hepatotoxicity risk, only certain patients with relatively healthy livers can receive the liver-targeted therapy. In a legacy problem caused by blood contamination in the past, some hemophilia patients who had received standard plasma-derived therapies developed hepatitis and excessive scarring of the liver that preclude them from being able to receive a gene therapy like Hemgenix, Young explained.Further, some people have prior exposure to adenoviruses and have developed preexisting neutralizing antibodies against AAV vectors that carry the therapeutic gene. Preexisting anti-AAV antibodies currently do not disqualify a patient from getting Hemgenix per the FDA’s label, but they may render the therapy less effective. Compared with Pfizer’s Beqvez, Hemgenix can tap into a broader population that doesn’t have that natural anti-AAV immunity, according to CSL.All considered, CSL estimates that about 1,000 U.S. patients stand to benefit from Hemgenix. A wait-and-see attitudeEven among those patients who meet all the eligibility criteria, only a small portion are ready to embrace the novel therapy.“The frustration is that we can’t get the community to be more enthusiastic about [Hemgenix],” Lojewski said.While some patients jumped on the opportunity to receive Hemgenix after seeing the data and the benefits it offers, others simply “don’t even want to talk about it,” Young explained.In the middle is a large group of patients who are taking a wait-and-see approach.“They basically are like, ‘This sounds really interesting, Dr. Young, but I’m not sure I want to be like the first one that you dose commercially,’” he observed.  Some of the hesitancy stems from an anxiety over safety that can be traced back to the infancy of gene therapy, Lojewski said. Some of it, as Young sees it, is classical behavioral economics, where only a few people want to be early adopters of a new technology.Another big reason behind Hemgenix’s slow rollout is that hemophilia—unlike many other rare diseases—has many existing treatment options that can keep the disease under control.Recombinant factor replacement therapies have been the mainstay hemophilia B treatment for decades. CSL is itself a seller of those traditional therapies, which are typically infused intravenously once or twice a week. The FDA has recently approved three more convenient subcutaneous treatment options, namely Pfizer’s Hympavzi, Novo Nordisk’s Alhemo and Sanofi’s Qfitlia, which can be dosed up to once every two months.For therapies that need to be administered repeatedly, a patient’s factor IX levels are expected to fluctuate, with a trough before the next dose.“What the gene therapies are offering is something altogether different,” Young said.Once Hemgenix delivers a functional copy of the factor IX gene, the body is expected to start producing factor IX in a stable manner. According to updated phase 3 data released in February from the Hope-B trial, Hemgenix produced mean factor IX levels of 36.7 IU/dL at year two, 38.6 IU/dL at year three and 37.4 IU/dL at year four. Although the definition of mild hemophilia puts a patient‘s factor IX level at 40 IU/dL, a rate in that neighborhood means patients won’t have bleeding episodes, Young explained. In the trial, the mean adjusted annualized bleeding rate went down from 4.16 from lead-in to 0.4 at year four post-treatment.The trial has yet to produce conclusive evidence to show whether Hemgenix can offer life-long benefits via one single infusion, but “it looks like it’s going to be durable,” Young said.Not all doctors share Young’s view that gene therapy offers an option that can fundamentally change patients’ lives.“What’s the rush” is one piece of feedback Lojewski has received from doctors.“I said, ‘but you do understand that companies won’t invest to develop therapies if there isn’t going to be a market for it,’” Lojewski recalled.Amid these discussions, Pfizer made its own decision to pull Beqvez.“You’ve got a good choice in front of you, if you don’t use it, then companies start to look other places to do research, and it would really be a shame for these patients if they didn’t have access to this therapy,” Lojewski said. A ‘fairly significant’ infrastructure barrierIf enthusiasm were lacking, then a “fairly significant” infrastructure barrier in the U.S. healthcare system, as explained by Young, represents yet another obstacle to Hemgenix’s uptake.For a physician at an institution that believes in Hemgenix’s value, it still took Young a year and a half to get internal clearance at Children’s Hospital Los Angeles (CHLA) to dose the gene therapy for the first time. For some doctors, it’s simply too much time and effort, Young acknowledged.To bring Hemgenix on board at CHLA, Young first convinced a pharmacy and therapeutics committee of the drug’s data profile. Then a high-cost drug committee worked out contracting to make sure that the institution is financially protected, as Hemgenix bears a list price of $3.5 million for one treatment.That high price is likely difficult for a small practice to stomach, Young noted, because as an infused therapy, Hemgenix is available under the buy-and-bill payment model. Under this model, the practice must first pay for the drug and then hope to get reimbursed later.In addition to those processes, a biosafety committee at CHLA also reviewed the proper ways to handle the product, which is regulated as a genetically modified organism under federal rules. Eventually, CSL staffers came over to train the pharmacists and nurses at the hospital. On the provider’s side, the treatment journey of Hemgenix involves a prescribing doctor like Young, a pharmacy that’s willing and able to store and mix the product, and a qualified infusion center that meets certain biosafety criteria.These three components may reside in different organizations, requiring additional coordination while creating some financial conflicts of interest.“Why we’re able to mobilize this and do it is because we’re all under one umbrella,” Young said.As an outpatient-administered gene therapy, Hemgenix comes with an automatic 23.1% discount under the federal 340B drug pricing program. That means, a provider site could pocket the $808,000 discount as profit if it purchased Hemgenix from CSL and got reimbursed from insurance at the original wholesale acquisition cost.Initially, CSL saw hospitals as wanting to buy the product. But once hospitals realized that only those infusion centers are eligible for 340B discounts, the company had to redo its purchase agreements with the hemophilia treatment centers instead.Facilities also dragged their feet because Hemgenix, as the first hemophilia gene therapy to reach the market, is responsible for setting the precedent.“They were trying to work through this in a way that made it so when other companies brought products to the market, that they weren’t going to be somehow financially harmed,” Lojewski said.  “There’s been a lot of just paperwork stuff, for lack of a better word, that had the community kind of entangled in, how do they navigate this,” Lojewski said.The CSL Behring team has also experienced instances in which treatment was delayed because the healthcare facility wanted to negotiate a higher level of reimbursement from payers.“It does feel a little bit frustrating to me when somebody’s willingness to administer therapy is dependent upon $70,000 more that they may or may not get in reimbursement,” Lojewski said.Given the large sums of money that facilities can make from administering Hemgenix, CSL has been perplexed about the tempered interest from potential customers.However, for a facility over the long term, the profit from years of chronic treatment may be higher than that from a one-time gene therapy, Lojewski noted.Lifetime healthcare costs for patients with moderate to severe hemophilia B can exceed $20 million, according to a 2021 Journal of Medical Economics article. CSL believes, at its current price, Hemgenix can save the US healthcare system $5 million to $5.8 million per person in a lifetime.Naturally, those savings would mean lost revenues to certain parts of the healthcare system. Lojewski said he hopes treatment decisions are not influenced by financial incentives. Positive signsDespite the challenges, CSL and Young are seeing improvements.Lately, different stakeholders have figured out how they’re going to divvy up the appropriate accountabilities and financial benefits amongst them, McKenzie noted during an investor call in February.“As the change was introduced, the hemophilia centers became more dependent on their hospital systems that they sit in for both infusion and pharmacy,” the CSL helmsman said on the call.“It’s taken some time for that to work through. But now, as those hospital systems work through that, they realize they can’t not have this offering for patients,” McKenzie continued. “It’s just too transformational to have the bureaucracy of the system have that.About 200 patients have gotten neutralizing antibody tests for potential Hemgenix treatment, according to CSL. Young recently received his first referral from a different state for Hemgenix.“Patients are going to start to demand, ‘I want the gene therapy,’ and if you can’t give it to me at your home center, then they’ll want to go to another center,” Young said.CSL’s Lojewski said the company’s target is to reach “about half of all prophylactic-treated patients.” While CSL believes it can reach that goal, “the question is the slope of the line,” Lojewski said.The institutional infrastructure-building for hemophilia gene therapy is heavily front-loaded, Young said. Once the logistics are set up and the needed experience is gained, Young expects the process will become easier and faster.CHLA is scheduled to treat its second Hemgenix patient on April 15.“I anticipate everything is going to go very smoothly,” Young said, “And then we’re off and running.”