CYTK aficamten

Obstructive HCM · Cytokinetics · sNDA

Of 100 applications in this same position, about 96 get approved.

Until the FDA deadline40d

Base rate95%

Gap+1pts

PDUFA target date 2026-11-14the FDA may act earlier or later

Summary

We put approval at 96%. This is a supplement to MYQORZO (aficamten), approved for obstructive HCM in December 2025, that asks FDA to add the MAPLE-HCM results to the label. MAPLE-HCM was clearly positive: aficamten monotherapy beat metoprolol on peak VO2 by 2.3 mL/kg/min (p<0.001), all key secondary endpoints were significant, and adverse events were similar (NEJM 2025). The drug, its REMS and its manufacturing are already approved, so the review raises few new questions. The main remaining risk is disagreement over comparative wording against metoprolol, which would more likely narrow the label than block approval. Confidence is high.

Recorded 2026-10-04 19:58 UTC · v1Proof ↓

Evidence · 4 items

Why it stays close to 95%

Indication

Efficacy supplement to NDA 219083 (MYQORZO, approved 2025-12-19 for adults with symptomatic obstructive HCM) to add the MAPLE-HCM results (aficamten monotherapy vs metoprolol monotherapy) to the label

95% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast stays close to it.

▲ supports approval, ▼ counts against it. More squares, more weight.

01▲ SupportsSmall The supporting trial is clearly positive

MAPLE-HCM (n=175, double-blind, double-dummy) found aficamten monotherapy better than metoprolol monotherapy on change in peak VO2 at week 24: +1.1 vs -1.2 mL/kg/min, difference 2.3 (95% CI 1.5 to 3.1), p<0.001. NYHA class, KCCQ-CSS, LVOT gradient, NT-proBNP and left atrial volume index were also significantly better. Published in NEJM.

Source: Garcia-Pavia et al., N Engl J Med 2025;393:949-960 (doi:10.1056/NEJMoa2504654); Cytokinetics 10-Q filed 2026-08-06
02▲ SupportsSmall No new safety or risk-management question for the reviewers

Adverse events looked similar in the aficamten and metoprolol arms. The drug already has a boxed warning for heart failure from systolic dysfunction and an echo-monitoring REMS (REMS supplement S-001 approved 2026-02-05). The supplement adds trial data to an existing indication rather than a new population.

Source: NEJM MAPLE-HCM; openFDA Drugs@FDA NDA219083; Cytokinetics 10-Q filed 2026-08-06
03▲ SupportsSmall The review division approved the original NDA in its first cycle, and nothing negative has been disclosed on this supplement

The original NDA was approved 2025-12-19 after a 3-month extension, which came because FDA asked mid-review for a REMS. FDA requested no new clinical data. The sNDA was submitted January 2026 and accepted with standard review and a PDUFA date of November 14, 2026. The August 2026 10-Q and the Q2 release report no extension, advisory committee or new FDA requests.

Source: Cytokinetics 8-K (Q1 2025 release) and Medthority on the 2025 extension; 8-K 2026-05-05; 10-Q filed 2026-08-06
04▼ AgainstSmall Possible disagreement over comparative-efficacy wording against metoprolol

Metoprolol is used off-label in HCM, and FDA is generally cautious about head-to-head superiority claims in labeling. If there is a disagreement, it would more likely narrow the Clinical Studies text than lead to a CRL. A narrower label still counts as approval.

Source: Analyst judgment; no public FDA statement on this sNDA

What would change this forecast

01
Disclosure of a PDUFA extension or of FDA requests for more analyses (an extension would mostly move the date)
02
A new postmarketing safety signal, such as heart-failure events coming through REMS or FOREST-HCM data, that changes how FDA views monotherapy use
03
Any company statement about label negotiations narrowing or dropping the MAPLE-HCM claims

Any change is published as a new version; earlier versions stay exactly as they were.

Confidence

High

Manufacturing and inspection risk

Low

The drug is a small-molecule tablet that has been made and sold commercially since January 2026 (US, EU and China approvals). The supplement is clinical/labeling only, so no new facility or process needs approval.

Record · version 1

Written on 2026-10-04, 41 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-04 19:58 UTC 96% Current version JSON ↓.ots ↓ ○ Timestamp submitted, awaiting block confirmation

Fingerprint

SHA-2564c8d43714826608cfff170e37b0f36f01b70a0ee2f14f32af38954a7771bf824

The fingerprint of the v1 file. It is what the timestamp commits to: change one character of the file and the fingerprint no longer matches.

Verify it yourself

Download the JSON file above and the .ots file of the same name into one folder.
Compute the SHA-256 of the file. It should match the fingerprint above.
Verify with OpenTimestamps. Once the timestamp is in a Bitcoin block, ots verify reports the block time if you run a Bitcoin node; without one, drop both files on the verifier at opentimestamps.org, or run ots info to see the block height and look it up in any block explorer. If the block time is before the FDA’s decision, the file cannot have been written afterwards.

pip install opentimestamps-client
shasum -a 256 v1_20261004T195807Z.json
ots verify v1_20261004T195807Z.json.ots
ots info v1_20261004T195807Z.json.ots

Scoring rule

What is scored is the last version recorded at least 2 days before the PDUFA target date; if the FDA decides early, only versions recorded before the day of its decision count. For this forecast the cutoff is 2026-11-12. Its error (also called the Brier score) is the squared distance between the forecast and the outcome, set against the error of quoting the base rate only.