Two Years After Rejection, Resilient Quietly Refiles MDMA for PTSD Application

Resilient has not publicly discussed the resubmission of its MDMA for PTSD NDA, but sources familiar with the filing have spoken with Psychedelic Alpha on condition of anonymity.

The resubmission comes almost exactly two years after FDA first rejected the package, issuing a Complete Response Letter (CRL) that became public last September.

That letter cited three dealbreakers. Put simply, the agency took issue with the company’s failure to collect ‘positive’ adverse events, insufficient durability data, and high rates of both prior MDMA use among participants and prescreening failures.

In its rejection letter, FDA went on to suggest that Resilient conduct a new trial to address these issues, focused on demonstrating durability, minimising the potential for bias, and better characterising the safety of the drug.

Rather than complete an entirely new Phase 3 study in-house, however, Resilient chose to reference other groups’ studies of its candidate, we understand. That data includes a small VA study with a long-term follow-up component, as well as at least one other third-party dataset.

A Memorandum of Understanding (MoU) between FDA and VA, announced last month, envisages data sharing between the two federal bodies. Given that it was apparently responsive to the Executive Order, it’s a safe bet that any data flows might include information from psychedelics studies, such as those trialling MDMA. (See VA-Assisted Label Expansion? for more.)

The company also ran a new Phase I study of its MDMA candidate in 32 healthy volunteers. Safety assessments in that trial include “monitoring of adverse events” as well as labs and cardiac-related measurements, like EKG and assessment of corrected QT interval, according to the registry entry. These were specifically recommended by the agency in its ‘additional comments’ in the CRL.

Elsewhere, Resilient conducted an audit of its Phase 3 data, as we have previously reported. (This was also disclosed publicly by the former FDA Commissioner, Marty Makary.)

Resilient is presumably hoping that it has addressed FDA’s dealbreakers, and it is now up to the agency to appraise the reconstituted package and decide whether to approve the MDMA candidate, which we understand may be called Rysanso if it reaches the market.

Some advocates believe that the NDA is a shoo-in, with political and cultural stars aligning in favour of approval. It is our understanding, however, that the Division of Psychiatry remains somewhat sheltered from those external forces, and is empowered as the ultimate decision-maker.

Given that it hasn’t yet completed a fresh Phase 3, Resilient may be open to a bit of back-and-forth with the Division, if the latter is inclined to approve the package in some form. In that scenario, the metes and bounds of a Risk Evaluation and Mitigation Strategy (REMS) program could become one bargaining chip.

Resilient could, for example, accept—or even propose—a tighter REMS than the one outlined by FDA in its June 2024 Advisory Committee meeting. That could feature elements like requiring recordings of all dosing sessions in the postmarketing context, we understand.

A more onerous REMS would have implications for scalability, however. While systems like the VA are likely to launch the drug no matter what, if it is approved by FDA and rescheduled by DEA, a resource-intensive REMS would certainly limit its uptake.

In terms of timelines, the appraisal of a resubmission is often quicker than that of a new submission, leaving many to wonder which psychedelic-related candidate might be the next to receive an approval decision from FDA.

We expect Compass Pathways and Usona Institute to both aim to submit psilocybin NDAs later this year. With Commissioner’s National Priority Vouchers in hand, their reviews could be as brief as 1-2 months.

As we reported this week, we also expect Definium Therapeutics to submit an LSD for generalised anxiety disorder (GAD) NDA in the first half of 2027. (Definium did not receive a voucher, despite a short-lived social media post from FDA appearing to suggest it had been in the running until the final hour.)

It’s perhaps too close to call, then, between Resilient and the psilocybin developers.

If an approval decision is handed down to Resilient’s MDMA for PTSD program, it is likely to attract plenty of attention. As we have noted previously, the fact that the CRL is in the public domain is likely to sharpen scrutiny in the case of an approval.

That is perhaps why Resilient has preferred to remain entirely silent, aside from communicating with potential funders throughout a modest fundraise. Its website, for example, features a GoDaddy domain parking page.

But in a way reminiscent of the original submission, back in 2024, Resilient’s nonprofit progenitor, the Multidisciplinary Association for Psychedelic Studies (MAPS), has gladly filled that void. (MAPS has no active role in Resilient’s day-to-day operations.)

Citing Psychedelic Alpha’s reporting, MAPS issued a press release on Monday responding to the news. It was keen to highlight that it had “initiated and funded the clinical research on MDMA-assisted therapy, completed in 2022, that the application builds on.”

“We believed the data was valid, that the therapists did their best treating the placebo subjects as well as the subjects who received MDMA, despite partial functional unblinding, and that adverse events and clinical outcomes were reported accurately,” MAPS founder Rick Doblin said in a statement, “though positive adverse events had not been gathered at that time.”

We continue to follow this story closely.