Compass Pathways' COMP360 Holds 13-Point MADRS Benefit at 52 Weeks in Phase 3 COMP005, NDA Submission Set for Q4
核心洞察
Compass Pathways reported 52-week open-label Part C data from Phase 3 COMP005 showing COMP360 produced an average 13-point MADRS reduction from baseline in the 25 mg arm.
Participants originally randomized to placebo who received their first 25 mg COMP360 dose in Part C achieved a mean 10-point MADRS reduction from baseline.
Across all Part C participants dosed at 25 mg, response rates were 40%-45% and remission rates approximately 30% between Day 1 and Week 6 after treatment.
Compass Pathways plc (Nasdaq: CMPS) reported topline 52-week results from Part C of its Phase 3 COMP005 trial of COMP360, a synthetic, proprietary formulation of psilocybin, in treatment-resistant depression (搜索) (TRD), with the open-label data showing sustained symptom reduction and a safety profile consistent with earlier phases of the study.
The COMP005 trial was a randomized, double-blind, placebo-controlled study that enrolled 258 participants in the United States and assessed the safety and efficacy of a single 25 mg dose of COMP360 versus placebo for reducing symptom severity in TRD (COMP360 25 mg: n=171; placebo: n=87). The trial allowed for a potential total of three doses of COMP360 across a 52-week period and was divided into three parts: Part A, blinded through Week 6, in which eligible participants were randomized 2:1 to a single 25 mg dose of COMP360 or placebo; Part B, blinded from Weeks 6 to 26, in which eligible participants could receive an additional dose of the same treatment to which they were originally randomized; and Part C, open-label from Week 26 to 52, in which eligible participants from both dosing arms could receive a single 25 mg dose.
Approximately 70% of study participants continued beyond Week 26 and entered Part C. In the 25 mg arm, approximately 80% (n=90) who entered Part C received an additional open-label dose — their second or third dose depending on whether they had received an additional dose in Part B. In the placebo arm, approximately 90% (n=52) who entered Part C received an open-label 25 mg dose, which was their first exposure to COMP360 25 mg after receiving placebo in Parts A and B.
Durability of Effect Through One Year
For participants originally randomized to the 25 mg arm who continued into Part C and received another dose, notable additional benefit was observed at all Part C timepoints through Week 52, with an additional meaningful reduction in MADRS beyond what had been observed in Parts A and B, yielding an average 13-point reduction from baseline at Week 52. Because these participants had one or two prior doses, the findings provide continued evidence that an additional dose of COMP360 25 mg may further deepen clinical response and extend durability out to one year.
For participants originally randomized to placebo who received their first 25 mg dose in the open-label portion, the data provide further evidence that a single dose of COMP360 25 mg has the potential to produce rapid onset, meaningful effect and durability, with a meaningful average reduction of 10 points from baseline in MADRS at the end of Part C from one dose.
"COMP360 has now demonstrated rapid onset, substantial magnitude of effect and sustained durability through one year with just a few doses. This emerging clinical profile is unmatched in TRD and puts COMP360 in a league of its own," said Kabir Nath, Chief Executive Officer of Compass Pathways.
Response and Remission Rates After Open-Label Dosing
Across all participants who received a 25 mg COMP360 dose in open-label Part C — whether they were originally in the placebo arm receiving their first dose or in the 25 mg arm receiving a second or third dose — response rates of 40% to 45% were observed between Day 1 and Week 6 following treatment. Responders were defined as those with a 50% or greater decrease in total MADRS score from baseline. Approximately 30% of these participants met criteria for remission over the same period, defined as a MADRS total score of 12 or less with no single item scored 4 or higher.
The COMP360 safety profile in Part C was consistent with Parts A and B, with the treatment continuing to demonstrate a generally well-tolerated and safe profile and no new safety signals observed.
"These 52-week results show COMP360, if approved, has the potential to be truly life changing for TRD patients. The consistent, rapid onset, pronounced magnitude of effect and durability to one year are remarkable to see, especially in such a chronic TRD population," said Dr. Guy Goodwin, Chief Medical Officer of Compass Pathways. "Across the 52-week study period, participants experienced cumulative and sustained reductions in depressive symptoms, which represent a significant advancement for the field."
Goodwin added that the open-label Part C trends, with continued benefit and high rates of response and remission, are believed to be a closer representation of how COMP360 will be used in real-world clinical practice.
Regulatory Path and Commercial Timeline
Compass has begun its rolling New Drug Application submission for COMP360 in TRD and expects to complete the submission in the fourth quarter, with a potential launch in the first half of next year, subject to FDA approval. The company noted that its rolling NDA submission and review are well underway.
"With a robust clinical package, and growing patient and provider anticipation for COMP360 as a much-needed treatment for TRD, Compass is well-positioned and ready to deliver," Nath said.
COMP360 holds Breakthrough Therapy designation from the FDA and Innovative Licensing and Access Pathway (ILAP) designation in the UK for TRD. The company notes that COMP360 contains Schedule I controlled substances and must be rescheduled by the Drug Enforcement Administration and states before it can be commercialized in the U.S., if approved by the FDA.
Broader Phase 3 Program and Unmet Need
The COMP360 program includes two pivotal Phase 3 trials, COMP005 and COMP006, evaluating the efficacy of COMP360 for TRD. The ongoing COMP006 trial is a randomized, double-blind study with 581 dosed participants across North America and Europe, comparing the efficacy and safety of two fixed doses taken three weeks apart of 25 mg COMP360 versus 10 mg COMP360 and 1 mg COMP360 (25 mg: n=296; 10 mg: n=142; 1 mg: n=143), with a potential for a total of four doses across a 52-week period. COMP006 comprises Part A, blinded through 9 weeks; Part B, which recently concluded and remained blinded through Week 26; and Part C, an open-label treatment part from Week 26 to 52.
TRD is broadly defined as an inadequate response to two or more appropriate courses of approved medications. It is estimated that approximately 4 million patients in the U.S. with major depressive disorder (搜索) live with TRD. Compared with non-treatment-resistant MDD, TRD has a significantly greater impact on individuals, leading to residual symptoms, poorer quality of life, increased comorbidities, higher mortality and an increased risk of suicide. Major depressive disorder was ranked as the third cause of the burden of disease worldwide in 2008 by the World Health Organization, which has projected that the disease will rank first by 2030.
Compass Pathways is headquartered in London, UK, with a U.S. office in New York. Beyond TRD, the company is executing a late-stage trial evaluating COMP360 for post-traumatic stress disorder (搜索) (PTSD).