The fate of Lykos’ MDMA treatment
I recently put together an article highlighting some of the more consequential FDA approvals — and rejections — so far this year. The article also noted some upcoming FDA decisions to watch — one of which is Lykos Therapeutics' midomafetamine (MDMA) capsules used in combination with psychological intervention for the treatment of PTSD.
There has been lot of excitement around this treatment because, if approved, it would be the first psychedelic-assisted therapy approved for PTSD and the first new treatment for PTSD in more than two deades. The PDUFA date is right around the corner (August 11) and while things are not looking ideal for the drug’s approval, Lykos is still pushing forward.
Things started to unravel back in March, when ICER, a nonprofit group that provides independent evaluations on the value of medical tests and treatments, published a report that highlighted placebo bias and ethical issues in Lykos’ data. ICER's final report was published in late June, and it echoed many of the concerns, including unblinding of a study, pointed out by the FDA advisory panel, who had rejected the drug weeks earlier.
Following its June 4 meeting, the FDA’s Psychopharmacologic Drugs Advisory Committee (PDAC) had voted against the MDMA treatment's approval on the grounds of both efficacy (2-9 against) and risk benefit (1-10 against).
Lykos, however, is still making plans for a potential approval and launch. Yesterday, the California-based biotech announced new initiatives and measures for additional oversight for the MDMA capsules, if approved.
Because Lykos took a novel approach with its new drug application — the NDA is the first to combine a drug and psychological intervention — the company is making sure to back that approach with additional oversight, including:
- Launching an independent advisory board to inform key elements of a potential commercial launch, including therapy training, ethics and health care integration
- Working with top behavioral health facilities to help ensure these sites are prepared to implement the measures utilized in Lykos' clinical trials
- Collaborating with other institutions around therapy training
The PDUFA clock is ticking, so the world will have its answer shortly — but something tells me even a rejection won’t deter Lykos from their commitment to bring psychedelics-based treatments to mental health patients. At the very least, they have paved a path for new approaches to mental health treatment and given regulators lots to consider. —Karen Langhauser
Pfizer gives up on DMD gene therapy
This week, Pfizer revealed significant layoffs and financial charges following the discontinuation of its Duchenne muscular dystrophy (DMD) program.
This comes weeks after a phase 3 trial for its investigational mini-dystrophin gene therapy, fordadistrogene movaparvovec, failed to meet primary or secondary endpoints. The CIFFREO trial showed no significant improvement in motor function among boys aged 4 to 7 compared to a placebo.
The program had been plagued with setbacks. A fatal serious adverse event was revealed in May in the phase 2 DAYLIGHT trial, which was evaluating fordadistrogene movaparvovec in younger DMD patients (aged 2-3 years). In response to the death in the DAYLIGHT trial, Pfizer paused dosing in the crossover portion of the subsequent phase 3 CIFFREO trial. This was the second pause for the CIFFREO trial, which had been halted in December 2021 due to the death of a patient in the non-ambulatory cohort of the phase 1b study. After that pause, Pfizer amended the trial protocol to include a seven-day hospital stay for monitoring post-dosing and resumed the study in March 2022.
As part of the fallout, Pfizer is cutting jobs at its Sanford, North Carolina site, the main hub for Duchenne research and gene therapy production. Approximately 150 employees involved in the Duchenne program and other site operations will be affected. The company is also taking a $230 million impairment charge related to the therapy's discontinuation and is considering selling a facility acquired from Abzena in 2023. This facility, initially scheduled to open by year-end, is now under review with no buyer identified yet.
In addition to these charges, Pfizer will record a $1.3 billion charge related to its Manufacturing Optimization Program, primarily for employee severance, and anticipates a $400 million charge in the third quarter of 2024 due to the planned sale of another facility impacted by the program's discontinuation.
The setbacks and eventual failure of Pfizer's DMD program will be a tough blow to the company's financial standing and workforce, underlining the difficulties in translating promising research into practical clinical solutions. But at the same time, Sarepta’s earlier success with Elevidys serves as a reminder that, despite numerous obstacles, perseverance and scientific progress continue to provide hope for patients with rare diseases. — Andrea Corona
