With Lykos CRL now public, FDA opens new era of accountability 

On September 4, 2025, the U.S. Food and Drug Administration (FDA) published a new batch of 89 Complete Response Letters (CRLs) as part of its ongoing transparency initiative. Among them was the CRL that, in August 2024, declined to approve Lykos’ application for MDMA-assisted therapy for post-traumatic stress disorder (PTSD).  

For the first time, the details of the FDA’s concerns over safety reporting, trial durability, and blinding are visible to the public. And that visibility has prompted a strong response: the Multidisciplinary Association for Psychedelic Studies (MAPS), which incubated Lykos, praised the FDA for making the letter public but sharply criticized its content, accusing the agency of “moving the goalposts” on trial standards. 

This might have implications well beyond psychedelics. As CRLs become increasingly accessible, FDA decisions are no longer confined to confidential exchanges with applicants. They can be examined, debated, and challenged by researchers, advocacy groups, and the public, raising the question of whether this new transparency could set a precedent for greater accountability in drug regulation. 

Lykos’ therapy, the trials, and the CRL 

MDMA-assisted therapy combines doses of midomafetamine (MDMA) with structured psychotherapy sessions and has long been championed by the nonprofit MAPS as a potential breakthrough for PTSD. To move the program through late-stage development and regulatory submission, MAPS created a public benefit corporation in 2014, later renamed Lykos Therapeutics in early 2024. The ties between the two remain close: MAPS describes itself as having “incubated” Lykos, while Lykos has carried the responsibility for regulatory filings and fundraising. More than a former incubator, MAPS retains notable oversight through the appointment of six out of the eight members of the Lykos Board of Directors. 

Expectations for approval were high. In 2017, the FDA granted the program Breakthrough Therapy Designation and, after negotiations, reached a Special Protocol Assessment agreement on the design of two pivotal phase 3 trials. These studies, known as MAPP1 and MAPP2, later reported positive results, with improvements on standard PTSD measures among patients receiving MDMA-assisted therapy compared with placebo. Yet, even before the regulatory filing was complete, FDA reviewers had expressed concerns about potential bias and the challenge of maintaining blinding in psychedelic studies. 

Those concerns came to the forefront at a meeting of the FDA’s Psychopharmacologic Drugs Advisory Committee in June 2024. The panel voted against the idea that the data provided “substantial evidence of effectiveness” and similarly concluded that the benefits did not outweigh the risks. Members cited functional unblinding, strong expectancy effects among participants, questions about generalizability, and gaps in safety monitoring. 

On August 9, 2024, the FDA followed that recommendation by issuing a Complete Response Letter to Lykos, declining approval of the therapy. The company acknowledged the decision at the time, saying it would work diligently in the coming months to address the FDA’s concerns. The rejection was widely covered in mainstream outlets as a significant setback for the field of psychedelic medicine, and it came in the midst of a storm of controversy: following the rejection, the journal Psychopharmacology retracted three published papers on MDMA studies due to what it called protocol violations amounting to unethical conduct. 

Lykos was undoubtedly hurt by the rejection of its MDMA-assisted therapy and had to cut 75% of its staff. The company is now in the process of rebranding itself once again as Resilient Pharmaceuticals. 

What was not available then, however, was the FDA’s detailed reasoning. That changed on September 4, 2025, when the agency published a redacted copy of the Lykos CRL as part of a broader release of 89 letters. For the first time, anyone can read the FDA’s full rationale: from the instructions given to trial sites not to record certain euphoria-like effects as adverse events, to concerns about the reliability of safety reporting, the lack of long-term efficacy data, and the influence of prior MDMA use among participants. This new transparency sets the stage for the current dispute, with MAPS welcoming the publication itself but arguing that the FDA had shifted its standards after agreeing on the trial design years earlier. 

While MAPS insists the FDA shifted its expectations after the trial design had been agreed upon, the agency maintains that the evidence provided was not sufficient to establish long-term efficacy or fully characterize safety. In the press conference following MAPS’ statement, Rick Doblin, MAPS’ founder, clarified that the organization was not part of the discussion with the FDA regarding Lykos’ therapy. It is too soon to know if the development of the debate will conclude that MAPS’ claims are legitimate, but regardless of the outcome of MAPS’ protest, the mere fact that this protest has been made possible because of the CRL’s publication is notable.  

FDA’s new transparency push 

Until recently, CRLs, the FDA’s detailed rejection letters listing flaws in drug or biologics submissions, remained private exchanges between the agency and applicants. Historically, sponsors controlled when and how much of this information reached investors, researchers, or the public. A 2015 FDA analysis even found that 85% of the FDA’s safety and efficacy concerns were omitted from companies’ public statements, and when the FDA requested additional trials for safety or efficacy, those requests went unmentioned in about 40% of cases. 

That changed on July 10, 2025, when the FDA launched what Commissioner Marty Makary called a move toward “radical transparency,” publishing more than 200 CRLs issued between 2020 and 2024. While most of these CRLs related to drugs that were ultimately approved, and thus were partly accessible already, the new effort regroups them into one public archive, aiming to reduce speculation and encourage greater predictability across the field. “For far too long, drug developers have been playing a guessing game,” Makary said. 

But the FDA didn’t stop there. On September 4, 2025, it dropped a second batch of 89 CRLs, this one including submissions still pending or withdrawn, and notably, the CRL for Lykos’ MDMA therapy. Alongside the release, the FDA reiterated its intention to publish CRLs promptly, going forward, signaling a shift from archival transparency toward real-time disclosure. 

Why does this matter? First, it is a departure from longstanding norms: regulatory reasoning is no longer negotiated behind closed doors. Instead, it can now be accessed, parsed, and debated by clinicians, investors, advocacy groups, and competitors alike. That can help level the playing field, but it also raises new questions about confidentiality. 

From closed doors to public scrutiny: what changes now? 

MAPS has seized on the CRL’s publication to argue that the FDA “moved the goalposts,” insisting that standards around blinding and trial design shifted only after the pivotal studies were complete. Whether or not that claim stands, the fact that it can be made openly is new.. Now, the FDA’s reasoning is accessible to anyone willing to read it, creating both opportunities and risks. While it does not mean the FDA will respond to MAPS’ concerns, it does allow for a broader public discussion. 

For psychedelic biotechs specifically, the Lykos letter may serve as a roadmap. Competitors such as COMPASS Pathways or ATAI Life Sciences can see for a fact, directly from the decision, what the FDA considered insufficient – durability of effect, blinding methods, safety reporting – and adapt their own programs accordingly. That visibility could accelerate the maturation of the field, even as it shows there is a higher bar that regulators expect.  

It could also temper some of the frustration that followed the initial rejection in 2024. Back then, coverage reflected disappointment and uncertainty about why the application had failed and created doubt about the entire field of psychedelics. With the Lykos CRL now public, the reasoning is spelled out, leaving less room for speculation and more scope for constructive debate. 

Indeed, Doblin said he was relieved about the publication of the Lykos CRL even though he disagreed with its content. “I feel the entire field has been getting the wrong message: that we should avoid therapy and favor psychological support. What’s best for the patient is getting the drug and the therapy. Regarding the possibility of creating a wider debate, while CRLs do allow for providing more context, the decision is still going to be between the FDA and the company directly. The benefit of the CRL being made public is that the field gets the message that the FDA simply wants a better understanding of the therapy that’s used.”  

The FDA, however, has stressed that its concerns are rooted in data reliability and patient safety. Both agree that it is about what’s best for the patient; they might not agree on what that is yet. 

The implications could extend beyond psychedelics. Investors and researchers now have direct access to failure points that previously remained hidden, which could change how capital is allocated and how trials are designed. Patients, too, gain a clearer view of why a therapy has been delayed or rejected, helping to demystify the regulatory process but also risking frustration if standards appear inconsistent from case to case. 

In short, transparency does not resolve disputes like the one between Lykos and the FDA, but it ensures they no longer happen entirely behind closed doors. Whether this new openness ultimately strengthens confidence in regulatory decision-making, or instead exposes the agency to greater criticism, will depend on how both sponsors and the FDA respond to this evolving scrutiny.