Warp speed: The next generation
The U.S. FDA’s rigid adherence to process has made it the gold standard of regulatory agencies. But at the same time, the agency, to its credit, has recognized that there is value in flexibility.
Specifically, speed. The flexibility the agency demonstrated during the pandemic with Emergency Use Authorizations and through Operation Warp Speed facilitated the rapid approval of safe vaccines and therapeutics when they were most needed.
Perhaps no area in medicine is more ripe with unmet need than rare disease. It is estimated that close to 95% of the identified 7,000+ rare diseases have no FDA-approved treatments.
I recall conducting an interview for a cover story a few years ago with Christian Rubio, who at the time was with the global rare disease nonprofit, Global Genes. Rubio referenced a startling piece of insight that has stuck with me ever since: Considering it has taken over 35 years to find treatment for roughly 250 rare diseases, if we continue at this rate, it will take approximately 2000 years to find cures for all the known rare diseases.
I was thrilled when the FDA officially launched the Support for Clinical Trials Advancing Rare Disease Therapeutics (START) pilot program last September, with the specific aim of facilitating more efficient development of potentially lifesaving therapies with rare disease indications. The pilot quickly picked up the nickname ‘Operation Warp Speed for Rare Diseases.’
In the same way that vaccine makers were in constant contact with the agency during the pandemic, the rare disease pilot program will allow for more frequent communication with FDA staff to provide a mechanism for addressing clinical development issues.
Participants were notified of their acceptance into the program on May 29, 2024. The agency recently confirmed to media sources that CBER has selected four initial participants and CDER has selected three. So far, six companies have announced that their programs have been chosen (read the details here):
Myrtelle (CBER program)
rAAV-Olig001-ASPA gene therapy
Canavan disease
Neurogene (CBER program)
NGN-401 gene therapy
Rett syndrome
Moderna (CBER program)
mRNA-3705 therapeutic
Methylmalonic acidemia
Larimar Therapeutics (CDER program)
nomlabofusp
Friedreich's ataxia
Denali Therapeutics (CDER program)
DNL126 enzyme replacement therapy
MPS IIIA (Sanfilippo syndrome type A)
Grace Science (CBER/CDER unspecified)
GS-100 gene therapy
NGLY1 deficiency
I’m anxious to hear more about the progression of these programs and hopeful that a successful START pilot will lead to more ‘warp speed’ therapeutics for patients who desperately need them. —Karen Langhauser
In the United States, PTSD affects approximately 6.8% of adults at some point in their lives, with about 3.6% of adults experiencing PTSD in any given year.
FDA Adcomm votes against MDMA for PTSD
In the United States, PTSD affects approximately 6.8% of adults at some point in their lives, with about 3.6% of adults experiencing PTSD in any given year.
In the last 20 years, pharmaceutical interventions for PTSD have included the development and approval of selective serotonin reuptake inhibitors (SSRIs), which have been shown to help alleviate symptoms. Recently, research has also focused on exploring novel pharmacological options such as MDMA-assisted therapy, ketamine, and other psychoactive substances to enhance therapeutic outcomes.
But earlier this year, an FDA advisory panel voted against approving Lykos Therapeutics' midomafetamine (MDMA) capsules in combination with psychological intervention for treating PTSD, citing concerns over efficacy and risk-benefit. The Psychopharmacologic Drugs Advisory Committee (PDAC) voted 2-9 against the treatment's effectiveness and 1-10 against the benefits outweighing the risks, even with the FDA's proposed risk evaluation and mitigation strategy.
The panel's decision was based on two randomized, double-blind, placebo-controlled phase 3 studies (MAPP1 and MAPP2) that evaluated the efficacy and safety of MDMA combined with psychological intervention versus placebo with psychological intervention in participants with severe or moderate to severe PTSD.
Although both studies met their primary and secondary endpoints, questions were raised before the advisory meeting regarding potential placebo bias and ethical issues, as highlighted in a report by the Institute for Clinical and Economic Review (ICER). The report suggested that therapists might have influenced patients to report favorable outcomes while discouraging negative reports, potentially biasing the recording of benefits and harms. Despite remaining mosly quiet on the matter, a group of investigators involved in the trials refuted the accusations made in the ICER report. The treatment currently has a PDUFA target action date of August 11, 2024.
While the development of new PTSD drugs faces significant challenges — including regulatory hurdles, potential side effects, and ethical concerns regarding patient treatment and data integrity — advancing these treatments would offer hope for more effective management of PTSD symptoms and improving the quality of life for millions affected by this debilitating condition. — Andrea Corona
