SVRA molgramostim

Autoimmune PAP · Savara · BLA

Of 100 applications in this same position, about 79 get approved.

Until the FDA deadline47d

Base rate76%

Gap+3pts

PDUFA target date 2026-11-22the FDA may act earlier or later

Summary

We put approval in this review cycle at 79%, slightly above the ~76% base rate for small/mid-cap original BLAs. The efficacy case is solid: IMPALA-2 met its primary DLCO endpoint (p=0.0007), the effect was durable at 48 weeks, SGRQ improved at week 24, and the drug has Breakthrough designation, Priority Review and no advisory committee. The main risk is manufacturing. This is a first-ever inhaled biologic and device combination; the first BLA was refused for incomplete CMC data; drug substance was moved to FUJIFILM Diosynth, which requires comparability; and a major amendment with undisclosed content pushed the date to November 22. Confidence is medium because the CMC picture is not public.

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

Evidence · 6 items

Why 79%, not 76%

Indication

Autoimmune pulmonary alveolar proteinosis (autoimmune PAP); molgramostim inhalation solution given once daily through a proprietary PARI eFlow nebulizer (drug-device combination)

76% of comparable applications were approved in the past: the opponent every forecast has to beat. Below are the reasons this forecast differs.

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

01▲ SupportsMedium The single pivotal Phase 3 trial hit its primary endpoint convincingly, and an earlier Phase 3 trial supports it

In IMPALA-2 (n=164, 1:1 vs placebo), the primary endpoint, change in hemoglobin-adjusted DLCO % predicted at week 24, improved by 6.0 points (p=0.0007). The gain held at week 48 (+6.9 points, p=0.0008). SGRQ total score at week 24 was also significant (-6.59, p=0.0072), but not at week 48 (p=0.10). SGRQ Activity and peak METs reached only nominal significance. Results were published in NEJM in August 2025. The earlier IMPALA Phase 3 trial gave supportive confirmatory evidence (A-aDO2 p=0.03 in a post-hoc imputation analysis; SGRQ p=0.01). When the FDA refused to file the first BLA in 2025, it did not ask for more efficacy studies.

Source: SEC 10-K filed 2026-03-13; Savara RTF press release 2025-05-27
02▲ SupportsSmall Expedited-review signals: Breakthrough Therapy, Priority Review, and no advisory committee

The product has Fast Track, Breakthrough Therapy and Orphan designations. The BLA was filed in February 2026 with Priority Review. The FDA's Day-74 letter said it had no plans to convene an advisory committee.

Source: Savara press release 2026-03-06; SEC 10-Q filed 2026-08-11
03▲ SupportsSmall Benign safety profile in a disease with no approved drug

Only 3% discontinued during the 48-week double-blind period, and no discontinuations were attributed to the trial drug. No unexpected safety signals were seen. Systemic GM-CSF (sargramostim) is a known drug class. A REMS is unlikely. The current standard of care is whole-lung lavage.

Source: SEC 10-K filed 2026-03-13; SEC 8-K 2026-01-09 (investor presentation)
04▼ AgainstMedium Complex manufacturing: first commercial product, a drug-device combination, and a drug-substance technology transfer after a CMC refuse-to-file

The March 2025 BLA was refused for filing in May 2025 because CMC data were incomplete. After a Type A meeting, Savara resubmitted in December 2025, naming FUJIFILM Diosynth as the drug-substance maker in place of the clinical-supply maker, GEMA Biotech. This requires showing comparability between GEMA and Fujifilm material, supported by three PPQ batches. Drug product is made at Patheon UK (Thermo Fisher). Pre-license inspections are needed, and CDRH must review the device constituent. My searches found no 2025-26 warning letters for Fujifilm's UK or Danish sites or for Patheon UK. Filings do not name the Fujifilm site.

Source: SEC 10-K filed 2026-03-13 (manufacturing strategy section); SEC 10-Q filed 2026-08-11 (manufacturing commitments)
05▼ AgainstSmall Three-month PDUFA extension for a major amendment; what the information requests covered was not disclosed

In April 2026 the FDA classified Savara's responses to its information requests as a major amendment, moving the date from 2026-08-22 to 2026-11-22. The company says the FDA cited no safety, efficacy or manufacturing concerns, which is standard wording. Given the earlier CMC refusal, the requests were plausibly about CMC or comparability, but that is not confirmed. Historically, extensions are not strongly negative.

Source: Savara press release 2026-04-15; SEC 10-Q filed 2026-05-12 and 2026-08-11
06▲ SupportsSmall Company behaviour is consistent with expecting approval

Q2 2026 G&A rose 78% as Savara built a commercial team for a planned launch. About $150M of non-dilutive capital becomes available on FDA approval. PSUs vest on BLA approval. Recent Form 4s show only RSU grants and tax withholding, with no open-market selling.

Source: SEC 10-Q filed 2026-08-11; Savara Q2 2026 results press release 2026-08-11; SEC Form 4 filed 2026-09-25

What would change this forecast

01
Disclosure of an FDA Form 483 or OAI classification at the Fujifilm drug-substance site or Patheon UK, or news that the major-amendment requests concerned GEMA-to-Fujifilm comparability
02
Company disclosure of late-cycle meeting outcomes or label negotiations (positive) or new FDA information requests close to the action date (negative)
03
An MHRA decision (expected Q4 2026) or a CHMP opinion: a positive one would be mildly reassuring on CMC, a negative one a material warning
04
Any further PDUFA extension, which would change the date but not by itself the probability

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

Confidence

Medium

Manufacturing and inspection risk

Medium

This is a small company's first commercial product: an inhaled recombinant protein given with a proprietary nebulizer. The drug-substance supplier was switched from the clinical-trial maker (GEMA) to FUJIFILM Diosynth after a CMC refuse-to-file, so analytical comparability and pre-license inspections of Fujifilm and Patheon UK must pass. Both are established CDMOs with no 2025-26 warning letters found. The content of the information requests behind the major amendment is not public, so the CMC risk cannot be judged directly.

Record · version 1

Written on 2026-10-04, 49 days before the PDUFA target date.

Timeline

Versions

v1 2026-10-04 19:58 UTC 79% Current version JSON ↓.ots ↓ ● Anchored in the Bitcoin blockchain

Fingerprint

SHA-25670f94ed35bdc3c030b513169724dde5ea39b78f7d65ce9fb5f7a7c9b096d461b

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_20261004T195810Z.json
ots verify v1_20261004T195810Z.json.ots
ots info v1_20261004T195810Z.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 2026-11-20. 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.