Replimune's RP1 Combination Therapy Gains FDA Momentum, Sparking 131% Rally

Replimune Group (REPL) shares have climbed approximately 131% over the past three months, driven by a significant milestone in its oncology pipeline. The catalyst? The FDA’s acceptance of a resubmitted biologics license application (BLA) for RP1 combined with Opdivo (nivolumab) in advanced melanoma treatment. With a decision target set for April 10, 2026, investors are gaining renewed confidence in the candidate’s regulatory pathway.

Regulatory Rebound: From Setback to Progress

The journey to this acceptance wasn’t straightforward. In July 2025, Replimune received a complete response letter (CRL) highlighting concerns about data consistency within the IGNYTE clinical study and questions regarding the study design’s rigor as a substantial evidence source. However, rather than a dead end, this became a turning point.

The company engaged in extensive FDA dialogue to address each concern point by point. By October 2025, Replimune submitted revised clinical documentation and additional analyses that successfully resolved the agency’s previous objections. The FDA subsequently confirmed the resubmission adequately addressed all outstanding issues, paving the way for Priority Review consideration.

This regulatory momentum has alleviated investor anxiety. Market participants now have tangible visibility into the approval timeline and can price in the potential launch scenario for 2026.

Clinical Evidence Building Confidence

Beyond regulatory acceptance, Replimune strengthened its clinical case with fresh data presented at the ESMO Congress in October. The most notable finding came from the acral melanoma subgroup, where the RP1/Opdivo combination demonstrated a 44% objective response rate with a median response duration of 11.9 months.

Acral melanoma—a particularly aggressive form affecting the palms, soles, and nail beds—has historically shown poor outcomes with standard immunotherapies. These results suggest the combination therapy may address an underserved patient population facing limited effective options.

The company is simultaneously advancing a larger phase III trial comparing RP1/Opdivo against physician-selected standard treatments in patients who have already progressed on anti-PD1 and anti-CTLA-4 regimens. Replimune has also disclosed encouraging safety and efficacy signals in non-melanoma skin cancers and is exploring RP1 as a monotherapy in immunocompromised transplant recipients.

Broader Pipeline Diversification

RP1 represents just one component of Replimune’s oncology strategy. The company is also advancing RP2, a second oncolytic immunotherapy candidate, in mid-to-late-stage studies targeting metastatic uveal melanoma and hepatocellular carcinoma. This diversification reduces pipeline risk and creates multiple value inflection points.

What Comes Next for REPL

The 131% three-month surge reflects investors repricing the approval probability upward. However, Replimune stock remains down 19.6% over the past year, suggesting the market is still cautiously optimistic rather than euphoric. The April 2026 FDA decision will likely be the defining moment for share trajectory in the near term.

For investors tracking clinical-stage biotech, Replimune’s combination of regulatory clarity, emerging clinical validation, and underpenetrated treatment niches makes it a name worth monitoring through 2026.