FDA Rejects Subcutaneous Amivantamab for NSCLC Over Manufacturing Concerns

The FDA has rejected the application from Johnson & Johnson for a subcutaneous version of its lung cancer drug amivantamab (Rybrevant) due to issues found during a routine preapproval inspection at a manufacturing facility, according to a news release.¹

The decision was outlined in a complete response letter (CRL) and does not question the drug’s safety, efficacy, or formulation; the FDA has not requested additional clinical trials.

The subcutaneous formulation of amivantamab was non-inferior to the IV version. | Image credit: Aliaksandr Marko – stock.adobe.com

J&J sought approval for the subcutaneous form of amivantamab to treat patients with advanced or metastatic non–small cell lung cancer (NSCLC) who have specific epidermal growth factor receptor (EGFR) mutations. The injectable formulation was expected to offer a more convenient option for patients, as it can be delivered under the skin rather than through lengthy intravenous (IV) infusions. The rejection does not affect the currently approved IV version of Rybrevant.

“We’re working closely with the FDA to bring [subcutaneous] amivantamab to patients as quickly as possible, and are confident in our path to resolution,” said Yusri Elsayed, MD, PhD, MHSc, global therapeutic area head for oncology and innovative medicine at J&J.

Amivantamab now joins a growing list of drugs receiving CRLs due to manufacturing facility issues. In June, the FDA rejected Merck and Daiichi Sankyo’s application for patritumab deruxtecan (HER3-DXd) to treat adults with previously treated locally advanced or metastatic EGFR-mutated NSCLC.² Similarly, the letter had no mention of any problems with the drug’s safety or efficacy data, but rather inspection findings at a third-party manufacturing facility.

In the myeloma space, Regeneron Pharmaceuticals also got a CRL for linvoseltamab to treat relapsed or refractory (R/R) multiple myeloma that has progressed following 3 or more prior therapies.³ This letter cited issues from a preapproval inspection at a third-party fill/finish manufacturer for a different company’s product candidate. According to Regeneron, the manufacturer believes it has resolved the issue and was awaiting reinspection as of August.

Promising Data for Amivantamab

Despite issues with the facility, the phase 3 PALOMA-3 trial yielded positive results, which showed that the subcutaneous formulation of amivantamab was noninferior to the IV version.¹ The trial evaluated the drug’s pharmacokinetics, efficacy, and safety in more than 400 patients with EGFR-mutated NSCLC who had progressed after treatment with osimertinib (Tagrisso) and chemotherapy.

Patients receiving the subcutaneous injection reported greater treatment convenience compared with the IV option, according to data presented at the 2024 American Society of Clinical Oncology Annual Meeting and published in the Journal of Clinical Oncology.⁴ Researchers highlighted that this method could reduce treatment burden for patients and health care providers by minimizing chair time and resource use.

Amivantamab is a bispecific antibody targeting the EGFR and MET pathways, and is approved in several countries as monotherapy and in combination with other therapies for specific EGFR-driven NSCLC mutations.¹ Its combination with lazertinib, a brain-penetrant tyrosine kinase inhibitor, has also demonstrated promising efficacy in improving progression-free survival for patients with EGFR exon 19 deletions and L858R mutations.

References

1. Update on U.S. regulatory review of subcutaneous amivantamab. News release. Johnson & Johnson. December 16, 2024. Accessed December 17, 2024. https://www.jnj.com/media-center/press-releases/update-on-u-s-regulatory-review-of-subcutaneous-amivantamab
2. Klein HE. FDA issues CRL for patritumab deruxtecan for locally advanced, metastatic EGFR-mutated NSCLC. AJMC^®. June 27, 2024. Accessed December 17, 2024. https://www.ajmc.com/view/fda-issues-crl-for-patritumab-deruxtecan-for-locally-advanced-metastatic-egfr-mutated-nsclc
3. Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605. doi:10.1200/JCO.24.01001
4. Klein HE. FDA issues CRL for linvoseltamab in R/R multiple myeloma. AJMC. August 21, 2024. Accessed December 17, 2024. https://www.ajmc.com/view/fda-issues-crl-for-linvoseltamab-in-r-r-multiple-myeloma