On May 7, 2024, Pfizer (PFE.US) sent a letter to the patient community, reporting the sudden death of a DMD patient in a Phase 2 clinical trial named DAYLIGHT. According to biopharma industry media Endpoints News, the patient passed away due to cardiac arrest.
Pfizer stated in the letter, "We do not yet have all the information and are actively working with the clinical trial site investigators to understand what happened." A spokesperson for Pfizer informed Endpoints that the company is reviewing data in collaboration with an independent external data monitoring committee.
The DAYLIGHT trial, as listed on the clinical trial registry ClinicalTrials.gov, aims to evaluate the safety and anti-DMD protein expression of the DMD candidate drug fordadistrogene movaparvovec, with patients primarily aged 2 and 3 years. The patient in question received treatment with fordadistrogene movaparvovec in early 2023.
DMD is an X-linked recessive genetic disorder caused by mutations in the Dystrophin gene on the X chromosome, affecting mainly boys. It typically manifests between ages 3-5, initially showing progressive weakness in leg muscles leading to difficulty in walking, loss of ambulation by age 12, and later complications such as cardiac and respiratory weakness during adolescence, often resulting in death by respiratory failure in the late 20s to 30s.
fordadistrogene movaparvovec is a gene therapy utilizing an adeno-associated virus serotype 9 (AAV9) vector, delivering a mini-Dystrophin gene to muscles via intravenous injection to partially restore muscle strength in patients.
Pfizer is also conducting a Phase 3 clinical trial named CIFFREO to assess the efficacy and safety of fordadistrogene movaparvovec, focusing on DMD patients aged 4-8 years. The initial dosing for this trial was completed in 2023. Following the patient's death, Pfizer decided to pause dosing in the crossover portion of the CIFFREO study but not in other trials involving fordadistrogene movaparvovec.
This marks the second time Pfizer has reported a death in clinical trials involving fordadistrogene movaparvovec. In 2021, Pfizer disclosed a death in an open-label Phase 1b study where a 16-year-old patient died from cardiogenic shock after receiving a higher dose of the treatment. Subsequently, the FDA halted the trial, lifting the clinical hold in April 2022, restricting the trial to ambulatory DMD patients and requiring a 7-day hospital stay for treated patients with close monitoring.
Currently, the only approved DMD gene therapy globally is Elevidys by U.S. biotech company Sarepta Therapeutics (SRPT.US), which received FDA approval in June 2023 for treating ambulatory DMD patients aged 4-5, priced at $3.2 million per dose.
Elevidys has also faced setbacks in its development. In its Phase 2 clinical trial assessments, both treatment and placebo groups did not show statistically significant differences, but Sarepta is pushing forward with a Phase 3 trial. In October 2023, Sarepta released results from the Phase 3 confirmatory clinical trial of Elevidys (EMBARK study), which did not meet the primary endpoint but did achieve secondary endpoints. Despite the trial's failure, Sarepta has applied to the FDA for expanded indications across all age groups.
