The Food and Drug Administration has rejected a rare-disease gene therapy from Regenxbio, the company said Monday. The Food and Drug Administration has rejected a rare-disease gene therapy from Regenxbio, the company said Monday. The one-time treatment, called RGX-121, is designed to replace a malfunctioning gene that causes mucopolysaccharidosis type II, also known as Hunter syndrome, an ultra-rare disorder that causes physical and cognitive impairments. RGX-121 is designed to replace a malfunctioning gene that causes mucopolysaccharidosis type II, also known as Hunter syndrome

Original title: “FDA rejects Regenxbio’s MPS II rare-disease gene therapy | STAT”

Regenxbio said on Monday the U.S. Food and Drug Administration had declined to approve its gene therapy for a rare disease called Hunter syndrome, citing uncertainty regarding the trial design. The potential next steps, which include a new study, treating additional patients and conducting longer-term follow up, "would be challenging in an ultra-rare disease population, like MPS II", the company said. The company plans to seek a meeting with the FDA on resubmitting its marketing application to provide further evidence on the patient population and additional longer-term clinical data. Hunter Syndrome is a genetic disorder in which the body cannot break down certain sugar molecules, which can affect physical and mental development. RGX-121 is a potential one-time gene therapy for the treatment of boys with MPS II, designed to deliver the gene which helps in breaking down complex sugar molecules. Feb 9 (Reuters) - Regenxbio (RGNX.O), opens new tab said on Monday the U.S. Food and Drug Administration had declined to approve its gene therapy for a rare disease called Hunter syndrome, citing uncertainty regarding the trial design. "We are concerned about FDA's feedback regarding the overall development path and evaluation of the data in the context of the urgent need for this irreversible ultra-rare disease," said CEO Curran Simpson. The health regulator last month placed a clinical hold on two of its experimental gene therapy programs that included RGX-121.

Original title: “US FDA declines to approve Regenxbio's gene therapy for rare disease | Reuters”

Regenxbio Inc. shares tumbled after US regulators rejected its gene therapy for Hunter syndrome, underscoring the hard line the Trump administration is taking on drug approvals for rare diseases. The Food and Drug Administration determined that Regenxbio’s clinical trial data wasn’t enough ... Regenxbio Inc. shares tumbled after US regulators rejected its gene therapy for Hunter syndrome, underscoring the hard line the Trump administration is taking on drug approvals for rare diseases. The Food and Drug Administration determined that Regenxbio’s clinical trial data wasn’t enough to support approval in the condition, which causes brain damage in boys, the company said in a statement Monday.

Original title: “FDA Denies Regenxbio Gene Therapy in Latest Rare Disease Setback - Bloomberg”

After facing a delayed decision deadline and a clinical hold, Regenxbio’s Hunter syndrome gene therapy has been rejected by the FDA. | After facing a delayed decision deadline and a clinical hold, Regenxbio’s Hunter syndrome gene therapy has been rejected by the FDA. The hold on the Hunter syndrome candidate came after a patient developed a brain tumor after being given a different gene therapy from Regenxbio. The potential for far-off side effects is why the field should focus on developing gene therapies for rare diseases, Wilson said, where the benefits of treatment easily outweigh the risks. Vinay Prasad, M.D., head of the FDA's Center for Biologics Evaluation and Research, which oversees gene therapies, has previously expressed ire over the use of biomarkers for approvals rather than placebo-controlled trials that measure clinical outcomes. Under Prasad's leadership, the FDA has also dealt surprise blows to uniQure's Huntington's disease gene therapy and Capricor Therapeutics' heart disease cell therapy. There are also ways that the patient’s underlying disease could have made the emergence of the tumor more likely, he said. “Integration would be necessary but not sufficient,” Wilson speculated. “There'd have to be something else that would contribute to that integration event leading to a tumor.” · Wilson cofounded Regenxbio back in 2009 and led animal studies of the gene therapies that became RGX-111 and RGX-121, he said, but has not worked on any of the clinical trials.

Original title: “FDA rejects Regenxbio gene therapy recently hit by clinical hold”

The announcement of the FDA’s ... therapy for MF. This regulatory milestone not only provides significant development incentives but also highlights the promising early clinical data from the zavabresib and ruxolitinib combination trial. For Opna Bio, this designation reinforces a commitment to addressing critical unmet needs in rare oncology through novel, targeted treatments... The announcement of the FDA’s Orphan Drug Designation for zavabresib underscores its potential as a transformative therapy for MF. This regulatory milestone not only provides significant development incentives but also highlights the promising early clinical data from the zavabresib and ruxolitinib combination trial. For Opna Bio, this designation reinforces a commitment to addressing critical unmet needs in rare oncology through novel, targeted treatments. The FDA granted Orphan Drug Designation to Opna Bio's zavabresib, a bromodomain and extra-terminal inhibitor, for treating myelofibrosis. “We believe that selective BET inhibition alongside JAK inhibition offers a promising new therapeutic approach for patients with myelofibrosis. We are further encouraged by recent positive meetings with the FDA to continue to test zavabresib in additional clinical studies,” Diaz concluded. This article originally appeared on Rare Disease Advisor ... Opna Bio announces orphan drug designation granted to OPN-2853 (zavabresib) for the treatment of myelofibrosis. This designation marks a significant regulatory milestone and underscores this promising treatment approach, emphasizing the unmet need for better therapies. MF is a rare, serious blood cancer involving bone marrow scarring that disrupts normal blood cell production, leading to anemia, fatigue, and splenomegaly. It affects around 25,000 people in the US. Current standard treatment often includes JAK inhibitors like ruxolitinib, but many patients eventually become resistant. Early evidence from an ongoing investigator-sponsored phase 1 trial (PROMise) combining zavabresib with ruxolitinib showed spleen length reduction of 50% or more in many patients previously unresponsive to ruxolitinib alone.

Original title: “FDA Grants Orphan Drug Status to Zavabresib for Myelofibrosis Therapy - Hematology Advisor”

Analysts, investors and scientists are eager for Biogen’s 2026 BIIB080 readout. Even if successful, executives warn that there are many more steps before the Alzheimer’s therapy could reach the market.

Original title: “Biogen’s Much Anticipated Tau Readout in Alzheimer’s Will Spur More Questions”

The gene therapy uses an AAV vector to restore healthy levels of the alpha-galactosidase enzyme, which is rendered dysfunctional in patients with Fabry disease, leading to the toxic build-up of lipids in cells.

Original title: “Liver Toxicities Force Pause on Two Dose Groups of UniQure’s Mid-Stage Fabry Study”

The FDA in July last year declined to approve UX111 for Sanfilippo syndrome, a rare neurodegenerative disorder, citing manufacturing issues. Ultragenyx resubmitted its application ten days ago, expecting a six month review time.

Original title: “Ultragenyx’s Gene Therapy Shows Long-Term Efficacy in Two Sanfilippo Studies”

Oral candidate shows favourable safety profile and signs of clinical activity in NPDR

Original title: “Strong clinical data for Breye lead asset danegaptide”

Sanofi’s rilzabrutinib wins FDA Breakthrough Therapy and Japan orphan status for warm autoimmune hemolytic anemia. Sanofi’s (SNY) rilzabrutinib has been granted breakthrough therapy designation in the United States and orphan drug status in Japan for treating warm autoimmune hemolytic anemia, the drugmaker said on Monday.

Original title: “Sanofi’s rilzabrutinib gains breakthrough therapy status in US, orphan drug designation in Japan (SNY:NASDAQ) | Seeking Alpha”

Sanofi’s rilzabrutinib wins FDA Breakthrough Therapy and Japan orphan status for warm autoimmune hemolytic anemia. Sanofi’s (SNY) rilzabrutinib has been granted breakthrough therapy designation in the United States and orphan drug status in Japan for treating warm autoimmune hemolytic anemia, the drugmaker said on Monday.

Original title: “Sanofi’s rilzabrutinib gains breakthrough therapy status in US, orphan drug designation in Japan (SNY:NASDAQ) | Seeking Alpha”

The US and Japan granted breakthrough therapy/orphan status to rilzabrutinib for wAIHA, a rare blood disorder marked by the destruction of red blood cells... These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successf The US Food and Drug Administration (FDA) has granted a designation as breakthrough therapy to Wayrilz (rilzabrutinib), a novel oral, reversible Bruton’s tyrosine kinase (BTK) inhibitor, for the treatment of patients with warm autoimmune hemolytic anemia (wAIHA), a rare autoimmune disorder marked by the destruction of red blood cells. The Japanese Ministry of Health, Labour and Welfare has also provided rilzabrutinib an orphan designation for the same condition. Other than the approved ITP indications in the US, EU, and UAE, these uses of rilzabrutinib are investigational and have not been evaluated by any regulatory authority. The FDA previously granted rilzabrutinib orphan drug designation for autoimmune hemolytic anemia, as well as two other rare diseases, IgG4-related disease (IgG4-RD) and sickle cell disease (SCD). Sanofi’s rilzabrutinib designated breakthrough therapy in the US and orphan drug in Japan for the treatment of warm autoimmune hemolytic anemia · Rilzabrutinib is the first and only investigational BTKi for warm autoimmune hemolytic anemia to be designated Breakthrough Therapy by the FDA

Original title: “Press Release: Sanofi’s rilzabrutinib designated breakthrough therapy in the US and orphan drug in Japan for the treatment of warm autoimmune hemolytic anemia”

False negative results from RCTs ... ultra-rare diseases. Rezolute’s experience developing a therapy in this setting serves as a case study illustrating both these limitations and potential approaches to overcoming them. Rezolute is studying its first-in-class monoclonal antibody therapy, ersodetug (“erso”), in two Phase 3 trials for the treatment of hypoglycemia ... False negative results from RCTs underscore the inadequacy of this “gold standard” for demonstrating therapeutic benefit in patients suffering from certain ultra-rare diseases. Rezolute’s experience developing a therapy in this setting serves as a case study illustrating both these limitations and potential approaches to overcoming them. Rezolute is studying its first-in-class monoclonal antibody therapy, ersodetug (“erso”), in two Phase 3 trials for the treatment of hypoglycemia resulting from separate but related forms of hyperinsulinism (HI). Our experience in tumor HI shows FDA is willing to set aside the RCT “gold standard” when other clinical evidence supports an alternative path. This demonstrates the agency’s emerging commitment to streamline the regulatory pathway for ultra-rare disease therapies. We hope FDA will continue to work with us and other industry partners in realizing the goal we all share: providing novel, safe, and effective treatments to individuals suffering from severe and debilitating ultra-rare diseases. A tale of different paths for different indications of the same disease It is well known within the biopharma industry that clinical studies can produce It is well known within the biopharma industry that clinical studies can produce any number of unexpected and possibly disappointing outcomes, including false negative results, or in statistical parlance, “Type II errors.” This is particularly true for clinical studies of therapies for ultra-rare diseases, where mechanistic plausibility may have already been demonstrated in open-label studies and expanded access programs (EAPs), but nonetheless must be replicated in randomized, double-blind, placebo-controlled studies (RCTs) that have narrow endpoints and small sample sizes.

Original title: “The conundrum of false negative clinical studies in ultra-rare diseases | STAT”

Roivant Sciences subsidiary Priovant Therapeutics licensed the dual JAK1 and TYK2 inhibitor from Pfizer. ... Rashes and lesions caused by cutaneous sarcoidosis can cover much of the body, sometimes becoming disfiguring. There are no FDA-approved treatments for this rare disease, which has been overlooked by much of the biopharmaceutical industry. According to Roivant Sciences, no industry-sponsored clinical trial ... Roivant Sciences subsidiary Priovant Therapeutics licensed the dual JAK1 and TYK2 inhibitor from Pfizer. ... Rashes and lesions caused by cutaneous sarcoidosis can cover much of the body, sometimes becoming disfiguring. There are no FDA-approved treatments for this rare disease, which has been overlooked by much of the biopharmaceutical industry. According to Roivant Sciences, no industry-sponsored clinical trial in this inflammatory skin disorder has succeeded — until now. Brepocitinib is on track for pivotal testing after meeting the goals of a proof-of-concept study in cutaneous sarcoidosis, a rare inflammatory skin disorder with no FDA-approved therapies. Roivant Sciences subsidiary Priovant Therapeutics licensed the dual JAK1 and TYK2 inhibitor from Pfizer. Priovant Therapeutics, a Roivant subsidiary, has preliminary results from a proof-of-concept Phase 2 study showing not only that many patients responded to treatment with its drug, brepocitinib, but also that many of them achieved clear or almost clear skin. Based on these results, the company is looking ahead to a Phase 3 study. The pill could reach the market sooner as a treatment for two other rare diseases. In rare disease, the unwanted effects of JAK inhibitors pose less of a barrier to developing a drug. Put another way, the tolerance for safety risks is higher simply because patients don’t have many, if any, treatment options. As an example, Gline pointed to the Phase 3 results for brepocitinib in dermatomyositis.

Original title: “Clinical Trial Win Bolsters Blockbuster Prospects for Roivant Rare Disease Drug Licensed From Pfizer - MedCity News”

Pharmacy Times offers the latest news and insights for the pharmacy professional and solutions that impact the everyday practice of pharmacy. The conversation begins with an overview of the current burden of ALL and limitations associated with traditional treatment approaches, setting the stage for how cellular therapies are reshaping care for patients with relapsed or refractory disease. The speakers then examine the mechanism of action and clinical trial data supporting obe-cel, highlighting how its design may influence efficacy and safety outcomes compared with earlier CAR T products. Throughout the discussion, the panel emphasizes practical considerations for pharmacists, including toxicity recognition and management, adverse event monitoring, and interdisciplinary coordination across transplant and cellular therapy teams. The episode underscores the critical role of oncology pharmacists in translating clinical trial evidence into real-world practice and supporting the safe integration of novel CAR T-cell therapies into evolving treatment paradigms for ALL. Tatyana Grgich, PharmD, BCOP, CPP, is a stem cell transplant and cell therapy pharmacist and pharmacy specialist at USC Medical Center. Jacqueline Del Pena, PharmD, is a clinical pharmacy specialist at Memorial Sloan Kettering Cancer Center, focusing on adult cell therapy services. Catie Cash, PharmD, BCOP, is a stem cell transplant and cell therapy pharmacist at Duke University Hospital. Rebecca Gonzalez, PharmD, BCOP, FASTCT, is a clinical pharmacist specialist in bone marrow transplant and cellular therapy at Moffitt Cancer Center.

Original title: “Pharmacist Takeover: CAR T Therapy Signals a Shift in ALL Treatment | Pharmacy Times”

Neurogene also relayed new preclinical findings on the use of intracerebroventricular and intrathecal lumbar delivery of NGN-401. received regenerative medicine advanced therapy (RMAT) designation from the FDA and was selected for the FDA’s Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program.2,3 Higher expression in key brain regions was seen with the ICV method both when ICV and IT-L used a dose that approximates the dose being used in human patients in the phase 1/2 trial (1 x 1015 vg) and when the IT-L method used a dose approximately 4 times higher than the clinically relevant dose being used with the ICV method. Neurogene also highlighted that in peripheral organs such as the liver, peripheral exposure of vector genome biodistribution was comparable to equivalent ICV and IT-L doses. “Feedback from the Rett syndrome community and key opinion leaders reinforces that the decision Importantly, the comparable systemic exposure between ICV and IT-L confirms there is no liver-sparing benefit to IT-L administration, consistent with clinical data from intra–cerebrospinal fluid administered products.” · Notably, in November 2024, a patient treated with NGN-401 in the phase 1/2 study · was reported to be in critical condition following a serious adverse event (SAE).4,5 The SAE, which · was previously reported by Neurogene as an emerging treatment-related SAE consistent with the known risks of AAV vector-based gene therapy, was then described as constituting signs of a rare and life-threatening immune response known as a systemic hyperinflammatory syndrome. Neurogene has finished talks with the FDA regarding the protocol for the registrational Embolden clinical trial to evaluate NGN-401, an investigational adeno-associated virus (AAV) vector-based gene therapy intended to treat Rett syndrome.1

Original title: “Neurogene Reaches Accord With FDA on Plan for Registrational Trial for Rett Syndrome Gene Therapy NGN-401 | CGTlive®”

Currently, ERT is the only treatment option for patients with Fabry disease – requiring patients to make a lifelong commitment to biweekly intravenous infusions at a dedicated healthcare centre. This data was presented at the WORLDSymposium in San Diego. While gene therapies have shown strong potential across a range of rare diseases, questions remain on the benefit-risk profile of some therapies, as multiple trials ... Currently, ERT is the only treatment option for patients with Fabry disease – requiring patients to make a lifelong commitment to biweekly intravenous infusions at a dedicated healthcare centre. This data was presented at the WORLDSymposium in San Diego. While gene therapies have shown strong potential across a range of rare diseases, questions remain on the benefit-risk profile of some therapies, as multiple trials have reported liver enzyme elevations in patients that have – in some cases – been fatal. uniQure will pause administration in the mid-to-high dose cohorts of the trial in Fabry disease, pending further evaluation. While a patient death following the event required Intellia to pause the trial initially, dosing later resumed in January 2026. Intellia CEO also confirmed that the AE was due to an infection and not ALI. Novartis’ AAV-based spinal muscular atrophy (SMA) drug, Zolgensma (onasemnogene abeparvovec-xioi) also caused two patient fatalities through acute liver failure. Cell & Gene therapy coverage on Clinical Trials Arena is supported by Cytiva. There were no additional serious treatment-emergent adverse events (TEAEs) reported in patients given the high dose, though patients given AMT-191 have previously experienced treatment-related chest pain and increased troponin levels. A patient treated with the gene therapy also developed a case of leptomeningeal enhancement, though it is currently unclear if this was associated with AMT-191. While AMT-191’s safety profile raises questions, the gene therapy did demonstrate early efficacy, as it triggered an elevation in α-galactosidase A (α-Gal A) activity, a key marker associated with Fabry disease across all three evaluated doses – 6×1013 genome copies/kilogram (gc/kg), 4×1013 gc/kg, and 2×1013 gc/kg.

Original title: “UniQure pauses dosing in Fabry disease trial amid safety concerns - Clinical Trials Arena”

Today's biotech news includes a heated rivalry between two eye drug companies, Novo and Hims facing off again over compounding, and more. And other biotech news brought to you by The Readout Sign up to get our biotech newsletter in your inbox. Good morning. We’ve made it to the end of what’s felt like an extremely long week. Wishing you all a restful weekend and lots of Super Bowl dips. ... Roivant and its spinout Priovant said this morning that their immune-modifying drug significantly outperformed placebo in clearing lesions caused by a rare skin disease in a small trial. Elaine Chen covers biotech, co-writes The Readout newsletter, and co-hosts STAT’s weekly biotech podcast, The Readout Loud.

Original title: “IPOs, GLP-1s, and challenges with a gene therapy”

According to Priovant, the Phase 2 BEACON study is the first industry-sponsored placebo-controlled trial in cutaneous sarcoidosis to deliver positive data.

Original title: “Priovant Plots Path to Phase 3 as Brepocitinib Clears Mid-Stage Skin Disease Study”

During the past decade, a total of 410 new molecular entities have been approved by the US Food and Drug Administration (FDA), with a steady growth of 6.5% in the US. In Europe, 9–75% of approved anticancer drugs were granted at least one expedited approval program. Various expedited pathways have also been implemented worldwide to address underrepresented medical needs rapidly. China has adapted several expedited approval programs, including breakthrough therapy designation, priority review, and conditional approval, to keep up with the growth in pharmaceutical development.

Original title: “An overview of cancer drugs approved through expedited approval programs and orphan medicine designation globally between 2011 and 2020 - ScienceDirect”