Five drugs have had PDUFA dates in the first ten days of April 2026. Four were resolved early — all approved. The fifth is different. It already failed once.
On April 10, the FDA will decide whether to approve vusolimogene oderparepvec (RP1) — Replimune's oncolytic immunotherapy for advanced melanoma. This is a Class II resubmission after a Complete Response Letter issued in July 2025. The FDA said no once. The question is whether the resubmission changed their mind.
What the FDA Said Last Time
The CRL was blunt. The FDA concluded that the IGNYTE Phase 1/2 trial — a single-arm study of 140 patients — was "not considered to be an adequate and well-controlled clinical investigation that could provide substantial evidence to support approval." No safety issues were raised. The concern was purely about evidence quality.
This matters because it frames the entire resubmission question. The clinical data didn't change. What changed was how Replimune presented it.
"The resubmission included additional information, data, and analyses."
— Replimune, October 20, 2025, on BLA resubmission acceptance
Additional analyses of the same data. Not new trials. Not more patients. A reframing.
The Evidence
Here is what the FDA is reviewing, updated through SITC 2025 (November):
Rate (RECIST 1.1)
Response Rate
of Response (months)
Survival
These are responses in patients whose melanoma already progressed on anti-PD-1 therapy — a population with limited options. Sixty-six percent had primary PD-1 resistance. Fifty-six percent were PD-L1 negative. Nearly half had already failed both anti-PD-1 and anti-CTLA-4.
The response is real. The question is whether 140 patients in a single-arm design constitute sufficient evidence.
The T-VEC Precedent
Only one oncolytic virus has ever been FDA-approved: Amgen's talimogene laherparepvec (T-VEC / Imlygic), approved October 27, 2015 for injectable melanoma lesions. RP1 is the second attempt.
| T-VEC (2015) | RP1 (2026) | |
|---|---|---|
| Trial design | Randomized Phase 3 (OPTiM, n=436) | Single-arm Phase 1/2 (IGNYTE, n=140) |
| ORR | 26.4% | 33.6% |
| Durable response rate | 16.3% | ~15% CR (different measure) |
| OS benefit shown? | No (trend only: 23.3 vs 18.9 mo) | Not designed to test (median NR) |
| Combination | Monotherapy | + nivolumab (anti-PD-1) |
| Patient population | Unresectable Stage IIIB-IV | Anti-PD-1 failed (harder population) |
| Advisory committee | 22-1 vote for approval | Not scheduled |
| Approval pathway | Full approval | Accelerated approval (sought) |
T-VEC had a randomized controlled trial with 436 patients. It still didn't show a statistically significant overall survival benefit. But an advisory panel voted 22-1 in its favor, and the FDA approved it.
RP1 has stronger response rates in a harder-to-treat population — but no randomized comparator. The confirmatory IGNYTE-3 Phase 3 trial (400 patients, OS primary endpoint) is enrolling now, with completion expected in 2029. The accelerated approval question is whether the existing data is enough to bridge to that readout.
The Resubmission Bet
Replimune's resubmission strategy rests on three pillars, based on data presented at ASCO and SITC 2025:
1. Durability
Median duration of response is 24.8 months — responses that last two years in a refractory population. PD-L1 negative patients (56% of trial) showed equivalent durability to PD-L1 positive, suggesting the mechanism works regardless of checkpoint status.
2. Deep Injection Data
Patients receiving deep/visceral injections showed 42.9% ORR vs. 29.8% for superficial-only. This suggests the drug works beyond the injection site — evidence of systemic anti-tumor immunity, which addresses the FDA's implicit concern about whether oncolytic viruses produce durable, whole-body responses.
3. Biomarker Reversal
Late-breaking SITC data showed RP1 upregulated gene signatures linked to PD-1 responsiveness and reversed multiple resistance mechanisms. In a population that failed anti-PD-1, this is mechanistically significant — it suggests RP1 re-sensitizes tumors to checkpoint inhibition.
The Odds
Analyst consensus is Buy with price targets ranging from $10–$19 (current ~$8). One estimate puts approval probability at 85%. REPL surged 86% when the BLA resubmission was accepted and gained another 7.2% on April 2.
But the optimism needs to be weighed against what hasn't changed: this is still a single-arm Phase 1/2, and the FDA explicitly said it wasn't enough last time. The acceptance of the resubmission confirms completeness, not approvability. Class II reviews are standard six-month timelines with no guarantee of a different outcome.
The Risk the Market May Be Underpricing
No CRL resubmission in melanoma has a guaranteed path. The FDA could issue a second CRL requiring data from the ongoing IGNYTE-3 Phase 3. If that happens, the next decision point is 2029 or later, and REPL's cash runway extends only into Q1 2027. A second rejection would be existential.
What I'm Watching
Seven days to PDUFA.
- Early approval signal. Four of five April PDUFAs came early. If RP1 is approved before April 10, it will likely surface as an after-hours FDA press release. But early approvals have all been for drugs with cleaner regulatory paths — early approval here would be the strongest bullish signal.
- Label language. If approved, watch whether it's monotherapy or specifically the RP1 + nivolumab combination. The IGNYTE trial tested the combination, and a combo-only label would mean Bristol-Myers Squibb's Opdivo (nivolumab) becomes a required co-prescription.
- Post-marketing requirements. Accelerated approval will come with a requirement for confirmatory evidence. Whether the FDA accepts IGNYTE-3's 2029 timeline or demands faster confirmation will determine commercial viability.
- Good Friday gap. NFP drops today (April 3, Good Friday). Markets are closed. Monday April 7 opens with three days of undigested macro data plus any weekend FDA activity. RP1 is three days after that.
Sources: Replimune IR, JCO (ASCO 2025), Targeted Oncology, FDA.gov, NCI (T-VEC history), CancerNetwork.