BioPharma, Pharma

FDA approval of J&J drug is first for lung cancer with particular genetic mutation

Johnson & Johnson subsidiary Janssen was awarded approval for Rybrevant, the latest in a string of decisions for targeted therapies for non-small cell lung cancer. Rybrevant is the first approved targeted therapy addressing a subset of patients whose disease is characterized by a particular mutation to cancer protein EGFR.


Lung cancer, the leading cause of cancer deaths, now has a new treatment for one of its rarest forms. The FDA has approved a Johnson & Johnson drug that attacks tumors characterized by a particular rare genetic mutation, making it the latest targeted therapy for the disease.

The drug, amivantamab, is a treatment for non-small cell lung cancer (NSCLC). The FDA decision Friday covers adults whose disease is characterized by an exon 20 insertion mutation to epidermal growth factor (EGFR), a cancer protein that causes rapid cell growth and helps tumors. Amivantamab is now the first drug approved by the agency to target this particular genetic signature.

Exon 20 insertion mutations to EGFR occur in about 2% to 3% of NSCLC patients, making it the third most common type of EGFR mutation, according to the FDA. Clinicians will detect that mutation using a companion diagnostic from Guardant Health that was also approved by the FDA on Friday.

Amivantamab, which J&J will market under the name “Rybrevant,” is a bispecific antibody that binds to both EGFR and MET, another protein expressed on the surface of NSCLC cells. The FDA based its decision on the results of an open-label clinical study enrolling 81 patients with NSCLC characterized by EGFR exon 20 insertion mutations that had progressed on or after chemotherapy. The main goal was to measure the overall response rate, which is the proportion of patients whose tumor was destroyed or shrunk by the study drug.

In the study, the subcutaneously infused drug showed an overall response rate of 40%. The median duration of that response was 11.1 months. Of those responding to treatment, 63% had response that lasted six months or longer. Results from the study were described in an abstract released in advance of the annual conference of the American Society of Clinical Oncology next month.

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The most common side effects reported in the study included rash, infusion-related reactions, skin infections around the fingernails or toenails, muscle and joint pain, shortness of breath, nausea, fatigue, and swelling in the lower legs or hands or face. The FDA added that treatment should be withheld if patients develop symptoms of interstitial lung disease, a condition that causes scarring in the lungs. If the disease is confirmed, use of the drug must end. The FDA also cautioned that the J&J drug may cause vision problems and can also harm a fetus.

Lung cancer, both small cell and non-small cell, is the second most common type of cancer in the U.S. after melanoma, according to the American Cancer Society. In the past year, several NSCLC therapies that target particular genetic signatures have secured regulatory nods. Last May, Novartis won the first such approval in NSCLC; its drug Tabrecta targets tumors that have mutations to the MET gene. That decision was followed by approvals awarded to Eli Lilly and partners Blueprint Medicines and Roche for drugs addressing NSCLC tumors characterized by genetic alterations to the RET gene. The string of approvals continued into 2021 with the February approval of EMD Serono drug Tepmetko, a kinase inhibitor that targets MET mutations.

FDA approval of J&J’s drug was conducted under Project Orbis, which offers companies a way to submit their cancer drugs for review concurrently with other regulators. The FDA review of Rybrevant was conducted in collaboration with regulators in Brazil and the U.K., where reviews are still ongoing. The FDA decision was an accelerated approval, which means J&J will be required to conduct additional clinical testing in to confirm the drug’s efficacy and to retain its approval status.

J&J isn’t the only company drug company aiming to treat NSCLC with EGFR exon 20 insertion mutations. Cullinan Oncology subsidiary Pearl is developing a tyrosine kinase inhibitor that targets the mutation. Cullinan licensed the compound from Taiho Pharmaceutical in 2019.

Photo: Jackie Niam, Getty Images