Sarepta Therapeutics has terminated a Phase I trial evaluating its gene therapy Elevidys (delandistrogene moxeparvovec) in combination with Hansa Biopharma’s Idefirix (imlifidase).
The study (NCT06241950) was evaluating whether using Idefirix would put Duchenne muscular dystrophy (DMD) patients with pre-existing IgG antibodies, which makes them ineligible to receive Elevidys, into the threshold to receive the gene therapy.
According to the listing on Clinicaltrials.gov, the trial has been terminated due to a “business decision”.
Clinical Trials Arena asked Sarepta for more information on the termination and what it meant for the partnership with Hansa but received no response.
Hansa presented data from three patients on the trial in August, showing that prior treatment with Idefirix did allow treatment with Elevidys, after patients experienced a rapid reduction of IgG antibodies to levels ≥95% less than baseline.
While the patients demonstrated evidence of AAV-mediated transduction and expression of micro-dystrophin 12 weeks after treatment with Elevidys, these were at levels lower than other patient populations reported at the same timestamp.
Idefirix is an antibody-cleaving enzyme that specifically targets IgG and inhibits an IgG-mediated immune response. Idefirix has a rapid onset of action, cleaving IgG-antibodies and inhibiting their reactivity within hours after administration, thus clearing the AAV-IgG antibodies that would typically preclude dosing or re-dosing with AAV.
When the companies shook hands in 2020, Hansa received an upfront payment of $10m and would have been eligible for additional development, regulatory and sales milestone payments potentially totalling up to $397.5m.
Hansa would also have retained all sales of Idefirix, as well as tiered royalties up to the mid-teens on any incremental gene therapy sales that arise from treating antibody-positive patients enabled through pre-treatment.
Latest disappointment for Sarepta
This latest termination adds to what has been a difficult year for Sarepta. The US Food and Drug Administration (FDA) put a number of pauses on the company’s trials involving the DMD therapy, as well as temporarily stopping sales and adding a black box label to the gene therapy following the death of two patients attributed to liver failure.
The company has also culled some of its pipeline after a 51-year-old man with limb-girdle muscular dystrophy (LGMD) type 2D/R3 died after being treated with Sarepta’s gene therapy candidate SRP-9004 in a Phase I trial.
Most recently, a pivotal trial of two of its DMD candidates, AMONDYS 45 (casimersen) and VYONDYS 53 (golodirsen) failed to show a statistical benefit compared to placebo in the primary endpoint. However, Sarepta added that there were numerical trends that favoured treatment over placebo.
Despite not reaching statistical significance, Sarepta said that armed with data from ESSENCE, real-world evidence, and the positive safety profile of AMONDYS 45 and VYONDYS 53, it intends to schedule a meeting with the FDA to discuss the possibility of converting from accelerated to traditional approval.
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