FDA Updates PDUFA Date of Subcutaneous Nivolumab

Bristol Myers Squibb recently announced that the US Food and Drug Administration (FDA) reassigned the previously determined Prescription Drug User Fee Act (PDUFA) action date of the biologics license application (BLA) for the subcutaneous formulation of nivolumab (Opdivo) to December 29, 2024. The original PDUFA date was February 28, 2025.¹

The subcutaneous formulation of nivolumab is co-formulated with Halozyme’s proprietary recombinant human hyaluronidase (rHuPH20) for all previously approved adult, solid tumor nivolumab indications as monotherapy, monotherapy maintenance following completion of nivolumab plus ipilimumab (Yervoy) combination therapy, or in combination with chemotherapy or cabozantinib.

The acceptance of Bristol Myers Squibb’s BLA is based on data from the phase 3 CheckMate-67T study where subcutaneous nivolumab demonstrated noninferiority of Cavgd28 (time-averaged nivolumab serum concentration over 28 days) and Cminss (trough serum concentration at steady state), the study’s co-primary endpoints, compared to intravenous (IV) nivolumab in patients with advanced or metastatic clear cell renal cell carcinoma who had received prior systemic therapy.²

In the key secondary end point, subcutaneous nivolumab showed noninferiority of objective response rate (ORR) compared to IV nivolumab. Additionally, the safety profile of subcutaneous nivolumab was consistent with the IV formulation.

“We believe subcutaneous nivolumab has the potential to make a significant difference in the lives of patients, which is reinforced by the FDA’s acceptance of our application. Opdivo is a foundational PD-1 inhibitor approved for many different types of cancer, and our continued investment in research that puts patients first remains a priority. If approved by the FDA, the subcutaneous administration of nivolumab would provide patients and their physicians with a new option that delivers the same well-known benefits as IV Opdivo but with the improved convenience of an injection administered in three-to-five minutes rather than a 30-to-60-minute infusion,” said Gina Fusaro, PhD, vice president and global program lead of Bristol Myers Squibb, in a previous news release.²

In October 2023, nivolumab was approved by the FDA for the treatment of patients with completely resected stage IIB or IIC melanoma. The FDA’s approval is based on results from the pivotal phase 3 CheckMate -76K trial, where nivolumab demonstrated a statistically significant and clinically meaningful benefit in recurrence-free survival versus placebo.³

Secondary end points of the phase 3 CheckMate -76K trial included overall survival, distant metastases-free survival, progression-free survival on next-line therapy, and safety end points.³

References

1. Bristol Myers Squibb announces updated action date by the U.S. Food and Drug Administration for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 21, 2024. Accessed May 22, 2024. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Announces-Updated-Action-Date-by-the-U.S.-Food-and-Drug-Administration-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx
2. U.S. Food and Drug Administration accepts Bristol Myers Squibb’s application for subcutaneous nivolumab (nivolumab and hyaluronidase). News release. Bristol Myers Squibb. May 6, 2024. Accessed May 22, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-Bristol-Myers-Squibbs-Application-for-Subcutaneous-Nivolumab-nivolumab-and-hyaluronidase/default.aspx
3. U.S. Food and Drug Administration approves Bristol Myers Squibb’s nivolumab for Opdivo (nivolumab) as an adjuvant treatment for patients with completely resected stage IIB or IIC melanoma. News release. Bristol Myers Squibb. October 13, 2023. Accessed May 22, 2024. https://news.bms.com/news/corporate-financial/2023/U.S.-Food-and-Drug-Administration-Approves-Opdivonivolumab-as-Adjuvant-Treatment-for-Eligible-Patients-with-Completely-Resected-Stage-IIB-or-Stage-IIC-Melanoma1/default.aspx