Pictured: FDA sign with blue sky backdrop/Adobe Stock, Grandbrothers
The FDA is racing toward four big decisions this week, including one in liver fibrosis due to non-alcoholic steatohepatitis and another that would mark the first gene therapy for Duchenne muscular dystrophy.
Argenx Seeks Approval of Subcutaneous Efgartigimod for gMG
On June 20, the FDA is set to decide on Argenx’s Biologics License Application (BLA) for subcutaneous (SC) efgartigimod (Vyvgart) as a treatment for adults with generalized myasthenia gravis (gMG).
Efgartigimod is a first-in-class antibody fragment that addresses gMG by targeting and binding to the neonatal Fc receptor, lowering the overall circulating levels of IgG. Generalized myasthenia gravis is an autoimmune disease that develops when a person’s IgG antibodies target the neuromuscular junction.
Efgartigimod first won the FDA’s approval in 2021 as an intravenous infusion for the treatment of adult gMG patients, based on data from the Phase III ADAPT study.
In its new BLA, which the FDA accepted in November 2022, Argenx highlighted efgartigimod’s co-formulation with Halozyme’s ENHANZE drug delivery technology, which uses recombinant human hyaluronidase PH20. ENHANZE allows the subcutaneous administration of medicines that are typically given intravenously.
Argenx also provided data from the ADAPT-SC study, which showed that the SC route of administration was non-inferior to an intravenous infusion in terms of IgG reduction at 29 days.
Efgartigimod’s SC application was given Priority Review by the FDA, with an initial target date of March 20, 2023. However, the FDA pushed back its review timeline in January following additional information from Argenx.
Aldeyra Pushes into Vitreoretinal Lymphoma
The FDA on June 21 will render its verdict on Aldeyra’s investigational intravitreal injection ADX-2191 (methotrexate injection, USP) for treating primary vitreoretinal lymphoma on June 21.
With 300 to 600 new diagnoses per year, primary vitreoretinal lymphoma is a rare and aggressive eye cancer that, when left unchecked, is potentially fatal. Patients diagnosed with the disease survive for a median of less than five years. While there are no approved primary vitreoretinal lymphoma treatments, patients are typically managed through intravitreal compounded methotrexate injections.
Aldeyra’s New Drug Application (NDA), which the FDA accepted in March 2023 and granted priority review, was backed by data from the Phase III GUARD study. The trial demonstrated that ADX-2191 was well-tolerated and did not lead to alarming safety issues, including treatment-emergent serious adverse events. The most common side effect observed in GUARD included punctate keratitis, which was often mild in severity.
ADX-2191 is also being investigated in Phase III for proliferative vitreoretinopathy and in Phase II for retinitis pigmentosa.
Intercept’s Obeticholic Acid Awaits FDA Decision in NASH
On June 22, the FDA will release make its decision regarding Intercept Pharmaceuticals’ obeticholic acid (OCA), which is being proposed for the treatment of patients with pre-cirrhotic liver fibrosis due to non-alcoholic steatohepatitis (NASH).
The New Jersey-based company is seeking accelerated approval for OCA using data from its NASH clinical development program, including two 18-month interim analyses from the Phase III REGENERATE study, a randomized, double-blinded, placebo-controlled study with more than 2,400 participants.
These analyses showed that the candidate improved liver enzyme levels and non-invasive measures of liver stiffness.
Last month, the FDA’s Gastrointestinal Drugs Advisory Committee refused to back OCA’s approval. Of the 16 panelists, only two found its benefit-risk profile favorable, while 12 disagreed; two advisors abstained. In particular, 15 panelists said the FDA should defer its approval until full results from REGENERATE come in. The study is expected to wrap up in September 2025.
This is Intercept’s second run at FDA approval for OCA. The company first submitted an NDA for 25-mg OCA oral tablets in September 2019. The regulator accepted this application in November 2019 but rejected it in June 2020, saying the predicted benefit of OCA based on surrogate histopathological endpoints is uncertain and did not sufficiently outweigh the potential risks.
Intercept resubmitted the NDA in December 2022, which the FDA accepted in January 2023.
Moment of Truth for Sarepta’s DMD Gene Therapy Hopeful
Following a three-week delay, Sarepta’s investigational gene therapy for Duchenne muscular dystrophy (DMD) is finally having its day at the FDA on June 22.
Sarepta’s candidate, SRP-9001 (delandistrogene moxeparvovec), works by delivering a functional copy of the dystrophin gene into a patient’s muscle tissues. In DMD, mutations in this gene manifest as the hallmark muscle weakness and developmental delay.
The Massachusetts-based biotech is seeking accelerated approval for SRP-9001 using biomarker data. In its data package—consisting of findings from three studies: SRP-9001-101, SRP-9001-102 and SRP-9001-103—the gene therapy candidate met various efficacy measures, including a significant improvement in concentrations of the novel micro-dystrophin indicator.
Sarepta claims this could indicate potential therapeutic efficacy. Still, the FDA is unconvinced, noting that measurement of micro-dystrophin levels “only provides information about expression of the transgene product in cells transduced by SRP-9001, rather than insight into a pharmacologic effect on a biomarker in the pathway of the disease,” according to briefing documents released in May 2023.
Compounding the regulator’s doubts is the fact that SRP-9001 missed its primary functional endpoint in one study, failing to induce statistically significant improvements in the North Star Ambulatory Assessment (NSAA) total score, which measures functional motor abilities in children with DMD.
Despite these apprehensions, an advisory committee voted 8–6 last month in narrow favor of Sarepta, recommending the accelerated approval of SRP-9001.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com
