Heroic Hearts & Healing Breakthrough Statement on the FDA’s complete response letter re: MDMA-Assisted Therapy
August 9, 2024 (Washington, D.C.) - The U.S. FDA has declined to approve MDMA-Assisted Therapy (MDMA-AT) for patients with post-traumatic stress disorder (PTSD), citing that it could not be approved based on data submitted to them.
As leading federal advocates for Veterans’ access toMDMA-AT), Healing Breakthrough & Heroic Hearts are deeply concerned by the FDA’s denial of Lykos’ NDA for MDMA-AT. This is the epitome of bureaucratic red tape – and the result is people will keep dying. MDMA-AT is the most effective treatment ever developed for PTSD, a condition at the core of the Veteran suicide crisis that claims over 17 lives each day.
The FDA’s decision is a missed opportunity to embrace groundbreaking science, save countless Veteran lives, and honor the sacrifices made by those who served our country. If this critical treatment remains inaccessible, we face losing an additional 6,000 Veterans to suicide this year alone—and every year thereafter.
Healing Breakthrough and Heroic Hearts Project will not relent. Our commitment to advocating for this life-saving treatment is unequivocal. We will continue to push for progress, collaborate with stakeholders, and fight persistently until MDMA-AT is available to every Veteran who desperately needs and deserves it.
Background Information:
The FDA has issued a Complete Response Letter (CRL) requesting that Lykos conduct an additional Phase 3 trial to further study the safety and efficacy of MDMA-Assisted Therapy (MDMA-AT).
Rather than aligning with the FDA’s own guidelines and guidance, the issues expressed in the CRL echo those raised during the FDA Advisory Committee meeting on June 4, 2024.
In so doing, the FDA has undermined its own regulatory integrity by subverting the agency’s stated guidelines, and apparently following politics, rather than science, in issuing what equates to a denial of Lykos’ NDA for MDMA-AT’s fast-track approval.
The data that Lykos included in its NDA provided more than sufficient evidence of MDMA-AT’s efficacy and durability, in line with the relevant FDA guidance.
FDA’s draft guidance for industry on psychedelic drugs indicates that endpoint data should be collected at 12 weeks.
Lykos’ Phase 3 studies went above and beyond the 12 week mark, and collected endpoint data at 18 weeks, with additional exploratory endpoints collected six months or more later.
In other words, Lykos both met and exceeded the FDA’s draft guidance in data collection regarding evidence of MDMA-AT’ efficacy and durability.
Moreover, Lykos had fully aligned with the FDA in its 2017 Special Protocol Assessment (“SPA”) on a variety of bias minimization measures in the study design.
The SPA was based on detailed dialogue with Lykos, making FDA a partner in the trial design.
The SPA process is an agreement resulting from official evaluation and written guidance from FDA on the protocol design, clinical endpoints, planned conduct, and statistical analyses for the Phase 3 trial, to ensure they are acceptable to support regulatory approval. Final marketing approval depends on the efficacy results, adverse event profile, and an evaluation of the ratio of risks and treatment benefits demonstrated in the Phase 3 clinical program.
The SPA agreement may only be changed through a written agreement between the sponsor and the FDA, or if the FDA becomes aware of a substantial scientific issue essential to product efficacy or safety (see the FDA’s Guidance for Industry.)
In response to Lykos’ NDA submission, the FDA replied, “We have completed our review and, based on the information submitted, agree that the design and planned analysis of your study adequately address the objectives necessary to support a regulatory submission.” [reference FDA-SPA-AgreementLetter 7-28-17, available online at https://maps.org/wp-content/uploads/2017/08/2017.07.28-IND063384FDA-SPA-AgreementLetter_Redacted.pdf]
The FDA changed the rules of the game arbitrarily, and without informing Lykos of any required changes as required by their own guidelines, resulting in a bait and switch in the review process that Lykos just learned about today.
The FDA was specifically aware that prior MDMA use was part of the trial design.
“In sponsor-supported PTSD studies in 107 participants treated with MDMA-assisted psychotherapy in a controlled clinical setting, 29.9% (32 of 107) of participants had tried Ecstasy at least six months prior to enrollment, with U.S. samples demonstrating a higher prevalence of use than international studies. ” [reference page 19, SPA Background Submission 19Jan17]
Nevertheless, the FDA rejected Lykos’ NDA on the basis of prior use of trial participants, without informing Lykos that a different trial design was required in order for approval to be considered.
FDA’s regulations commit to following its Agreements and to giving timely notice when it believes conditions have changed: “FDA makes every effort throughout the product development process to communicate to sponsors any concerns regarding relevant new information that may affect FDA’s thinking regarding an SPA agreement as soon as it is appropriate and feasible to do so.” [reference: Special Protocol Assessment Guidance for Industry, April 2018 at p. 17, available at https://www.fda.gov/media/97618/download].
In this case, the FDA did not follow their own guidelines or protocols, as it neither informed Lykos of any changed conditions or requirements for approval to be considered.
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