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Replimune Gets Second FDA CRL for Melanoma Drug BLA, Stock Crashes
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Key Takeaways
Replimune shares fell 63% pre-market after the FDA issued a second CRL for RP1 melanoma BLA.
FDA cited IGNYTE study design flaws and data issues, though no safety concerns were raised.
Replimune warns that delays may force cuts, scaling back ops and jeopardizing RP1 development.
Replimune Group’s (REPL - Free Report) share price is down 63% in the pre-market hours today after the company announced that the FDA has issued a second complete response letter (CRL) against its resubmitted biologics license application (BLA) seeking accelerated approval for its lead pipeline asset, RP1 (vusolimogene oderparepvec), in combination with Bristol Myers’ (BMY - Free Report) Opdivo (nivolumab) to treat adult patients with advanced melanoma.
Please note that the first CRL against the RP1 BLA for the melanoma indication was issued in July last year by the FDA. The regulatory agency stated that data from the IGNYTE study, submitted in support of the application, failed to meet its standards for an adequate and well-controlled clinical investigation, preventing approval of the BLA in its current form. The agency noted that the IGNYTE study results were difficult to interpret due to the heterogeneity of the patient population and highlighted shortcomings in the ongoing confirmatory study’s design, particularly regarding the contribution of components. However, the FDA raised no safety concerns.
The second CRL has cast significant uncertainty on the regulatory path for RP1, which Replimune had positioned as a potential near-term growth driver in a high-need oncology market. It has also significantly delayed REPL’s prospects of bringing its first approved product to market, postponing the opportunity to establish a steady revenue stream. The sharp decline reflects both the near-term disruption to Replimune’s development timeline and broader investor concerns about the company’s ability to deliver on its lead program.
REPL Disputes FDA Second CRL on RP1 BLA for Melanoma
Replimune has pushed back against the FDA’s second CRL for its resubmitted BLA for RP1 in advanced melanoma, arguing that the dataset supporting the therapy remains adequate for accelerated approval. The company maintains that the same body of evidence had previously supported the therapy’s breakthrough designation and continues to demonstrate meaningful clinical benefit. Data from the IGNYTE study showed that patients who had progressed on prior anti-PD-1 therapies achieved a 34% response rate when treated with RP1 in combination with BMY’s Opdivo, with responses lasting a median of 24.8 months and a favorable safety profile.
The company also highlighted broader implications of the FDA’s decision, noting that the lack of regulatory flexibility could delay access to a potentially beneficial therapy for patients with limited treatment options. It indicated that, without a viable accelerated approval pathway, continued development of RP1 may not be sustainable, prompting restructuring measures including job cuts and a scaling back of U.S.-based manufacturing operations.
Replimune further raised concerns about inconsistencies in the regulatory review process. It noted that a new review team was assigned to evaluate the resubmission, replacing the original team that had engaged with the company earlier. The company suggested that internal differences in interpretation within the agency may have contributed to the outcome, and pointed out that the new review team did not engage in discussions during the review despite outreach efforts.
Year to date, shares of Replimune have crashed 51% against the industry’s 0.9% growth.
Image Source: Zacks Investment Research
The company argued that the FDA’s latest stance contradicts feedback provided during prior regulatory interactions. It cited earlier alignment on issues such as patient population heterogeneity and the impracticality of including an anti-PD-1 monotherapy control arm in the confirmatory study. Replimune also stated that it had followed agency guidance in submitting additional analyses from the IGNYTE and IGNYTE-3 studies, including progression-free survival comparisons and component contribution assessments, but did not receive feedback before the CRL was issued.
On methodological concerns, Replimune emphasized that tumor responses were assessed using RECIST 1.1 criteria as requested, and that additional analyses demonstrated consistent efficacy across injected and non-injected lesions, with no meaningful impact from biopsies or surgical interventions. It also underscored that earlier regulatory discussions had supported the use of single-arm study data for accelerated approval if sufficiently compelling, which formed the basis of the original BLA submission that had been accepted for priority review. Following FDA guidance, the company had also launched a resource-intensive global phase III IGNYTE-3 study to meet the requirement of having a confirmatory study in progress for accelerated approval.
Bristol Myers’ blockbuster immuno-oncology drug Opdivo is approved, both as a monotherapy and in combination with Yervoy, to treat a plethora of cancer indications in many countries, including the United States and the EU.
Apart from the melanoma indication, REPL is studying the combo therapy in a separate cohort of the IGNYTE study for several non-melanoma skin cancer indications. The company is also evaluating RP1 as a monotherapy in solid organ transplant recipients with skin cancers.
Replimune also has a second candidate in its clinical-stage pipeline, which is currently being evaluated in two separate mid-stage studies for skin and liver cancer indications.
Over the past 60 days, estimates for Catalyst Pharmaceuticals’ 2026 EPS have increased from $2.55 to $2.87. CPRX shares have gained 6.9% year to date.
Catalyst Pharmaceuticals’ earnings beat estimates in each of the trailing four quarters, with the average surprise being 35.19%.
Over the past 60 days, estimates for ADMA Biologics’ 2026 EPS have increased from 85 cents to 96 cents. ADMA shares have plummeted 46.9% year to date.
ADMA Biologics’ earnings beat estimates in one of the trailing three quarters, matched once and missed on the remaining occasion, with the average negative surprise being 1.79%.
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Replimune Gets Second FDA CRL for Melanoma Drug BLA, Stock Crashes
Key Takeaways
Replimune Group’s (REPL - Free Report) share price is down 63% in the pre-market hours today after the company announced that the FDA has issued a second complete response letter (CRL) against its resubmitted biologics license application (BLA) seeking accelerated approval for its lead pipeline asset, RP1 (vusolimogene oderparepvec), in combination with Bristol Myers’ (BMY - Free Report) Opdivo (nivolumab) to treat adult patients with advanced melanoma.
Please note that the first CRL against the RP1 BLA for the melanoma indication was issued in July last year by the FDA. The regulatory agency stated that data from the IGNYTE study, submitted in support of the application, failed to meet its standards for an adequate and well-controlled clinical investigation, preventing approval of the BLA in its current form. The agency noted that the IGNYTE study results were difficult to interpret due to the heterogeneity of the patient population and highlighted shortcomings in the ongoing confirmatory study’s design, particularly regarding the contribution of components. However, the FDA raised no safety concerns.
The second CRL has cast significant uncertainty on the regulatory path for RP1, which Replimune had positioned as a potential near-term growth driver in a high-need oncology market. It has also significantly delayed REPL’s prospects of bringing its first approved product to market, postponing the opportunity to establish a steady revenue stream. The sharp decline reflects both the near-term disruption to Replimune’s development timeline and broader investor concerns about the company’s ability to deliver on its lead program.
REPL Disputes FDA Second CRL on RP1 BLA for Melanoma
Replimune has pushed back against the FDA’s second CRL for its resubmitted BLA for RP1 in advanced melanoma, arguing that the dataset supporting the therapy remains adequate for accelerated approval. The company maintains that the same body of evidence had previously supported the therapy’s breakthrough designation and continues to demonstrate meaningful clinical benefit. Data from the IGNYTE study showed that patients who had progressed on prior anti-PD-1 therapies achieved a 34% response rate when treated with RP1 in combination with BMY’s Opdivo, with responses lasting a median of 24.8 months and a favorable safety profile.
The company also highlighted broader implications of the FDA’s decision, noting that the lack of regulatory flexibility could delay access to a potentially beneficial therapy for patients with limited treatment options. It indicated that, without a viable accelerated approval pathway, continued development of RP1 may not be sustainable, prompting restructuring measures including job cuts and a scaling back of U.S.-based manufacturing operations.
Replimune further raised concerns about inconsistencies in the regulatory review process. It noted that a new review team was assigned to evaluate the resubmission, replacing the original team that had engaged with the company earlier. The company suggested that internal differences in interpretation within the agency may have contributed to the outcome, and pointed out that the new review team did not engage in discussions during the review despite outreach efforts.
Year to date, shares of Replimune have crashed 51% against the industry’s 0.9% growth.
Image Source: Zacks Investment Research
The company argued that the FDA’s latest stance contradicts feedback provided during prior regulatory interactions. It cited earlier alignment on issues such as patient population heterogeneity and the impracticality of including an anti-PD-1 monotherapy control arm in the confirmatory study. Replimune also stated that it had followed agency guidance in submitting additional analyses from the IGNYTE and IGNYTE-3 studies, including progression-free survival comparisons and component contribution assessments, but did not receive feedback before the CRL was issued.
On methodological concerns, Replimune emphasized that tumor responses were assessed using RECIST 1.1 criteria as requested, and that additional analyses demonstrated consistent efficacy across injected and non-injected lesions, with no meaningful impact from biopsies or surgical interventions. It also underscored that earlier regulatory discussions had supported the use of single-arm study data for accelerated approval if sufficiently compelling, which formed the basis of the original BLA submission that had been accepted for priority review. Following FDA guidance, the company had also launched a resource-intensive global phase III IGNYTE-3 study to meet the requirement of having a confirmatory study in progress for accelerated approval.
Bristol Myers’ blockbuster immuno-oncology drug Opdivo is approved, both as a monotherapy and in combination with Yervoy, to treat a plethora of cancer indications in many countries, including the United States and the EU.
Apart from the melanoma indication, REPL is studying the combo therapy in a separate cohort of the IGNYTE study for several non-melanoma skin cancer indications. The company is also evaluating RP1 as a monotherapy in solid organ transplant recipients with skin cancers.
Replimune also has a second candidate in its clinical-stage pipeline, which is currently being evaluated in two separate mid-stage studies for skin and liver cancer indications.
Replimune Group, Inc. Price and Consensus
Replimune Group, Inc. price-consensus-chart | Replimune Group, Inc. Quote
REPL Zacks Rank & Stocks to Consider
REPL carries a Zacks Rank #3 (Hold) at present.
Some better-ranked stocks in the biotech sector are Catalyst Pharmaceuticals (CPRX - Free Report) and ADMA Biologics (ADMA - Free Report) , sporting a Zacks Rank #1 (Strong Buy) each at present. You can see the complete list of today’s Zacks #1 Rank stocks here.
Over the past 60 days, estimates for Catalyst Pharmaceuticals’ 2026 EPS have increased from $2.55 to $2.87. CPRX shares have gained 6.9% year to date.
Catalyst Pharmaceuticals’ earnings beat estimates in each of the trailing four quarters, with the average surprise being 35.19%.
Over the past 60 days, estimates for ADMA Biologics’ 2026 EPS have increased from 85 cents to 96 cents. ADMA shares have plummeted 46.9% year to date.
ADMA Biologics’ earnings beat estimates in one of the trailing three quarters, matched once and missed on the remaining occasion, with the average negative surprise being 1.79%.