REGENXBIO Secures $250 Million Royalty Monetization Deal to Advance Gene Therapy Pipeline
• REGENXBIO has closed a non-dilutive royalty bond agreement with Healthcare Royalty for up to $250 million, receiving $150 million upfront that extends its cash runway into early 2027.
• The deal monetizes select royalties from ZOLGENSMA for SMA and payments from gene therapies for MPS disorders, while REGENXBIO retains other funding opportunities including a potential Priority Review Voucher.
• This strategic financing supports REGENXBIO's late-stage pipeline development, including RGX-121 for MPS II, RGX-202 for Duchenne muscular dystrophy, and ABBV-RGX-314 for wet AMD.
Vertex Pharmaceuticals Abandons AAV Vector Technology Amid Broader Industry Retreat from Gene Therapy
• Vertex Pharmaceuticals has discontinued all research on adeno-associated virus (AAV) vector technology, impacting partnerships with Affinia Therapeutics and Tevard Biosciences focused on Duchenne muscular dystrophy treatments.
• The retreat from AAV vectors follows a broader industry trend, with Pfizer, Roche, Takeda, and Biogen all scaling back gene therapy programs due to safety concerns, limited payload capacity, and high manufacturing costs.
• Despite industry pullback, companies like Affinia Therapeutics continue developing next-generation AAV vectors, while others explore alternative delivery systems such as Herpes simplex virus-1 vectors with larger genetic payloads.
FDA Commissioner Makary Proposes New Approval Pathway for Rare Disease Drugs
• FDA Commissioner Marty Makary has announced plans for a new regulatory pathway to expedite approvals for rare disease treatments, potentially without requiring randomized controlled trials.
• The proposed "plausible mechanism" pathway would include conditional approvals for therapies with scientifically sound physiological rationales, coupled with a comprehensive patient surveillance system.
• Makary also addressed public distrust in health authorities, announcing plans to replace the self-reported VAERS system with a more robust "Health Information Exchange" to better monitor treatment complications.
Epicrispr Biotechnologies Secures $68 Million to Advance First Epigenetic Therapy for FSHD
• Epicrispr Biotechnologies has raised $68 million in Series B funding to develop EPI-321, a first-in-class epigenetic therapy targeting facioscapulohumeral muscular dystrophy (FSHD).
• New Zealand's Medsafe has approved Epicrispr's clinical trial application, with the first-in-human study of EPI-321 expected to begin in 2025 to evaluate its safety and biological activity in adults with FSHD.
• EPI-321 uses CRISPR technology to silence the DUX4 gene that drives FSHD progression and has received FDA Fast Track, Rare Pediatric Disease, and Orphan Drug designations.
Ionis Advances Antisense Therapy for Angelman Syndrome to Phase 3 Following Promising Clinical Results
• Ionis Pharmaceuticals is moving forward with Phase 3 trials for ION582, an antisense therapy designed to unsilence the paternal UBE3A gene in Angelman syndrome patients, after Biogen declined to license the drug.
• In the Phase 1/2 HALOS study, 97% of participants receiving medium or high doses of ION582 showed improvements in communication, cognition, and motor function, with favorable safety profiles.
• The race to develop treatments for Angelman syndrome is intensifying, with Ultragenyx's GTX-102 already in Phase 3 trials and Neuren Pharmaceuticals advancing an oral synthetic peptide, highlighting significant progress in addressing this rare genetic disorder.
UK Faces Growing Challenges in Access to Rare Disease Medicines Despite Recent Approvals
• Recent data reveals a concerning trend as UK drops from 2nd to 10th place in European rankings for orphan medicine availability, signaling declining access to rare disease treatments.
• Analysis shows over 100% increase in terminated NICE appraisals over the past decade, with rates rising from 9.8% (2016-2019) to 20.1% (2020-2023), limiting patient access to licensed medicines.
• Industry survey indicates 11 out of 18 pharmaceutical companies expect to launch less than 75% of their rare disease pipeline in the UK, citing unfavorable reimbursement environment and high payment rates.
Ultragenyx Announces Positive 2024 Revenue and Advances Rare Disease Pipeline
• Ultragenyx reported preliminary 2024 revenue of $555 million to $560 million, exceeding previous guidance, driven by strong sales of Crysvita and Dojolvi.
• The company anticipates total revenue between $640 million and $670 million in 2025, projecting continued growth and pipeline advancement.
• Key clinical programs are progressing, including setrusumab for osteogenesis imperfecta (Phase 3) and GTX-102 for Angelman syndrome (Phase 3).
• Ultragenyx expects a PDUFA decision for UX111 in Sanfilippo syndrome type A and plans to file a BLA for DTX401 in Glycogen Storage Disease Type Ia in 2025.
Ersodetug Receives FDA Breakthrough Therapy Designation for Congenital Hyperinsulinism
• The FDA granted Breakthrough Therapy Designation to Rezolute's ersodetug for treating hypoglycemia due to congenital hyperinsulinism.
• The designation is based on Phase 2b (RIZE) study results, showing significant hypoglycemia improvements without clinically significant hyperglycemia.
• Ersodetug is advancing in Phase 3 trials for congenital and tumor-induced hyperinsulinism, with topline sunRIZE data expected in the second half of this year.
• Rezolute's antibody therapy targets all forms of hyperinsulinism, demonstrating benefits in clinical trials and real-world use.
Eli Lilly Seeks to Join Lawsuit on Compounded Drugs
Eli Lilly aims to join a lawsuit as a defendant against a compounding trade group's litigation with the FDA over the status of its drug tirzepatide, arguing it needs to protect its interests and ensure the swift resolution of the case.
Key Biotech Clinical Trials and Developments to Watch in the First Quarter
The first quarter sees significant biotech developments with Ultragenyx and Praxis Precision Medicines leading the charge. Ultragenyx is advancing its Phase 3 study on setrusumab for osteogenesis imperfecta, while Praxis Precision Medicines is set to report on ulixacaltamide for essential tremor.
Ultragenyx Doses First Patient in Phase 3 Aspire Study of GTX-102 for Angelman Syndrome
• Ultragenyx has initiated the Phase 3 Aspire study to evaluate GTX-102 for Angelman syndrome, a rare neurogenetic disorder.
• The Aspire study will enroll 120 children aged 4-17 with Angelman syndrome, assessing cognitive and motor function improvements.
• GTX-102 is an investigational antisense oligonucleotide designed to restore UBE3A protein expression by targeting UBE3A-AS.
• The Aurora study is planned for 2025 to evaluate GTX-102 in other Angelman syndrome genotypes and age groups.
Ultragenyx's UX111 Gene Therapy for Sanfilippo Syndrome Type A Receives FDA Priority Review
• The FDA has granted priority review to Ultragenyx's Biologics License Application (BLA) for UX111, a gene therapy for Sanfilippo syndrome type A (MPS IIIA).
• The FDA's decision is expected by August 18, 2025, and the agency is not planning an advisory committee meeting for this application.
• UX111 has demonstrated statistically significant improvements in cognitive and communication skills, correlated with reduced heparan sulfate levels in cerebrospinal fluid.
• UX111, if approved, would be the first-ever treatment for Sanfilippo syndrome type A, addressing a critical unmet need for this rare, neurodegenerative disease.
Mereo BioPharma's Setrusumab Phase 3 Trial Progresses; Alvelestat Receives Positive EMA Opinion
• Mereo BioPharma's setrusumab Phase 3 Orbit study for osteogenesis imperfecta is ongoing, with a second interim analysis expected in mid-2025.
• Alvelestat, for Alpha-1 Antitrypsin Deficiency-associated Lung Disease, received a positive EMA opinion on its European Orphan Designation application.
• The European Commission is expected to make a final decision on Alvelestat's Orphan Designation in the first quarter of 2025.
• Mereo BioPharma's current cash and cash equivalents are expected to fund operations into 2027, covering key milestones.
Advancements in Gene and Cell Therapies Target Diverse Diseases
• Ultragenyx seeks accelerated FDA approval for UX111, a gene therapy for MPSIII, based on Phase 1/2/3 trial data.
• Arbor Biotechnologies' CRISPR-based therapy ABO-101 receives clearance for US trial in Primary Hyperoxaluria Type 1.
• Allogene Therapeutics' ALLO-329 cleared by FDA for Phase 1 trial in rheumatology indications including lupus.
• uniQure progresses in trial for SOD1-ALS gene therapy AMT-162, advancing to the second cohort enrollment.
Gene Therapy Advances: From FDA Clearances to Clinical Trial Progress in Early 2025
• The FDA cleared United Therapeutics' UKidney for US trials, a gene-edited porcine kidney product intended for end-stage renal disease via xenotransplant.
• uniQure received the green light to proceed with the second dose cohort in their Phase 1/2 trial of AMT-162 for SOD1-ALS gene therapy.
• Sarepta Therapeutics' Elevidys showed sustained benefit in ambulatory patients with Duchenne muscular dystrophy in Phase 3 trial results.
FDA Accepts Abeona's BLA Resubmission for Pz-Cel in Recessive Dystrophic Epidermolysis Bullosa
• The FDA has accepted Abeona Therapeutics' resubmitted Biologics License Application (BLA) for pz-cel, a gene therapy for recessive dystrophic epidermolysis bullosa (RDEB).
• The FDA set a PDUFA target action date of April 29, 2025, for the decision on pz-cel, an autologous, cell-based gene therapy.
• The BLA resubmission addresses Chemistry, Manufacturing, and Controls (CMC) issues raised in a previous Complete Response Letter, with no new clinical data requested.
• Pz-cel has shown significant wound healing and pain reduction in Phase 3 trials, potentially addressing unmet needs for RDEB patients.
Liso-cel Demonstrates Significant Response in Relapsed/Refractory Marginal Zone Lymphoma
• Bristol Myers Squibb's liso-cel achieved a statistically significant and clinically meaningful overall response rate in patients with relapsed or refractory marginal zone lymphoma.
• The Phase 2 trial results highlight the potential of liso-cel as an effective treatment option for this challenging patient population.
• The data were presented at the 2025 Tandem Meetings, showcasing advancements in cell therapy for hematological malignancies.
Abeona Therapeutics Resubmits BLA for Pz-cel in Recessive Dystrophic Epidermolysis Bullosa
• Abeona Therapeutics has resubmitted its Biologics License Application (BLA) to the FDA for prademagene zamikeracel (pz-cel) for recessive dystrophic epidermolysis bullosa (RDEB).
• The resubmission addresses Chemistry Manufacturing and Controls (CMC) requirements requested by the FDA, with no concerns raised regarding clinical safety or efficacy.
• Pz-cel, an autologous cell-based gene therapy, has shown promising results in Phase 3 and Phase 1/2a trials, demonstrating wound healing and pain reduction.
• The FDA is expected to set a new target action date upon acceptance, with a review period of two to six months for the resubmitted BLA.
FDA's Accelerated Approval Pathway Faces Scrutiny Amidst Withdrawals and Biomarker Concerns
• The FDA's accelerated approval program, designed to expedite drug availability, faces increased scrutiny due to recent high-profile withdrawals, including Pfizer's Oxbryta.
• Experts are raising concerns about the reliability of surrogate endpoints and the timeliness of confirmatory trials required for maintaining accelerated approvals.
• There is a call for better understanding and validation of biomarkers used in accelerated approvals, especially in complex diseases like Alzheimer's and ALS.
• Proposed solutions include stricter deadlines for confirmatory trials and addressing potential biases in the FDA's funding structure to ensure unbiased judgment.
FDA's Accelerated Approval Pathway Faces Scrutiny as Some Drugs are Withdrawn
• Several drugs approved under the FDA's accelerated approval pathway have been withdrawn from the market due to safety concerns or failure to confirm clinical benefit.
• Pfizer pulled Oxbryta, a sickle cell disease therapy, after new data showed a higher risk of deaths and complications in treated patients.
• Biogen and Eisai discontinued Aduhelm, an Alzheimer's drug, after a controversial approval and inauspicious rollout, focusing instead on Leqembi.
• The FDA is now requiring confirmatory trials to be underway before granting accelerated approval to address delays and ensure clinical outcomes.
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