Will the FDA approve AXS-12 in cataplexy associated with narcolepsy before 31 May 2027?
deadline 2027-05-31
confidence medium
tier 4 evidence
36%Asturna estimate
⚠ Evidence cap applied: the model proposed 42%, brought back to 36% for lack of sources solid enough to justify the departure from the base rate.
Resolution criterion
Yes if the FDA approves the NDA by 31 May 2027 (Drugs@FDA or an Axsome release). A complete response letter, a postponed PDUFA date, or no decision by that date all count as no.
Verified starting state
NDA accepted, PDUFA date 1 May 2027, no advisory committee planned. SYMPHONY trial: 83% reduction in weekly attacks against 66% on placebo (p = 0.018). ENCORE randomised-withdrawal trial: +10.29 attacks per week on placebo against +1.32 on continued treatment (p = 0.017). The very high placebo effect makes the therapeutic margin narrow. (15 July 2026)
What pushes it up
- The FDA has accepted the NDA for AXS-12 and set a PDUFA date of May 1, 2027, which falls before the resolution deadline [1].
- Two Phase 3 trials (SYMPHONY and ENCORE) met their primary endpoints with statistical significance (p=0.018 and p=0.017 respectively) [1].
- The FDA has stated it does not currently plan to hold an advisory committee meeting for this application, which often indicates fewer perceived regulatory hurdles [1].
What pushes it down
- The therapeutic margin is narrow due to a very high placebo effect observed in the SYMPHONY trial (83% reduction for AXS-12 vs 66% for placebo) [1].
- The statistical significance in the pivotal trials is relatively modest (p-values > 0.01), which may lead to closer scrutiny of the clinical meaningfulness [1].
- The resolution deadline is only 30 days after the PDUFA date; any major amendment or 3-month extension would result in a 'No' resolution [1].
- Reboxetine has a history of mixed efficacy results in other indications and a significant number of serious safety reports in the FAERS database [1].
What would move this number most
The primary uncertainty is whether the FDA will consider the modest absolute improvement over a high placebo response to be clinically significant enough for approval in the first review cycle.
How this number is built
| Deadline | 2027-05-31 |
| Base rate | 28% |
| Best evidence | tier 4 · 5 article(s) used |
| Independent runs | 36 · 36 (spread 0 pts) |
| Confidence | medium |
| Evidence cap | applied: 42% brought back to 36% |
| Last revised | 2026-10-07 09:12 |
| Model | gemini-3-flash-preview |
Sources consulted
Probability history
2026-10-07 09:12 36% 10 article(s) on file · gemini-3-flash-preview
- What pushes it up. The FDA has accepted the NDA for AXS-12 and set a PDUFA date of May 1, 2027, which falls before the resolution deadline [1].
- What pushes it up. Two Phase 3 trials (SYMPHONY and ENCORE) met their primary endpoints with statistical significance (p=0.018 and p=0.017 respectively) [1].
- What pushes it up. The FDA has stated it does not currently plan to hold an advisory committee meeting for this application, which often indicates fewer perceived regulatory hurdles [1].
- What pushes it down. The therapeutic margin is narrow due to a very high placebo effect observed in the SYMPHONY trial (83% reduction for AXS-12 vs 66% for placebo) [1].
- What pushes it down. The statistical significance in the pivotal trials is relatively modest (p-values > 0.01), which may lead to closer scrutiny of the clinical meaningfulness [1].
- What pushes it down. The resolution deadline is only 30 days after the PDUFA date; any major amendment or 3-month extension would result in a 'No' resolution [1].
- What pushes it down. Reboxetine has a history of mixed efficacy results in other indications and a significant number of serious safety reports in the FAERS database [1].
- What would move this number most. The primary uncertainty is whether the FDA will consider the modest absolute improvement over a high placebo response to be clinically significant enough for approval in the first review cycle.
2026-09-21 22:28 35% 9 article(s) on file · openai/gpt-oss-120b (Groq)
Reasons not recorded for this revision (detailed history has only been kept since recently).
2026-09-20 09:00 83% 7 article(s) on file · gemini-3-flash-preview
Reasons not recorded for this revision (detailed history has only been kept since recently).