FDA Approves J&J's Rybrevant and Lazcluze Combo for NSCLC

The U.S. Food and Drug Administration (FDA) has granted approval to Johnson & Johnson’s (J&J) Rybrevant (amivantamab-vmjw) in combination with Lazcluze (lazertinib) as a first-line therapy for certain types of non-small cell lung cancer (NSCLC). This approval is specifically for patients with locally advanced or metastatic NSCLC characterized by epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R substitution mutations, identifiable through an FDA-approved diagnostic test.

The FDA’s decision is rooted in findings from the Phase III MARIPOSA study (NCT04487080), which compared the efficacy of the Rybrevant/Lazcluze combination against AstraZeneca’s Tagrisso (osimertinib). The study data revealed that the combination therapy of Rybrevant and Lazcluze decreased the risk of disease progression or death by 30% in comparison to Tagrisso alone. Moreover, the median duration of response for the combination treatment was nine months longer than that for Tagrisso.

The MARIPOSA study achieved its primary endpoint, which was progression-free survival (PFS), and also met additional secondary endpoints, which included various participant demographics such as race, type of EGFR mutation, and history of brain metastasis. These results underscored the clinically significant advantages of the Rybrevant/Lazcluze combination over Tagrisso.

J&J submitted a supplemental biologics license application (sBLA) and a new drug application (NDA) to the FDA for this particular indication in December 2023. Prior to this, in March 2024, the FDA had already approved Rybrevant in combination with carboplatin-pemetrexed chemotherapy for first-line treatment of locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.

Johnson & Johnson highlighted that this drug combination is the first and only multitargeted, chemotherapy-free regimen that has shown superiority over Tagrisso. This new approval is expected to introduce significant competition for AstraZeneca. Both Rybrevant and Tagrisso are designed to target and inhibit specific mutations in the EGFR gene, a frequent target in NSCLC. Tagrisso generated $5.8 billion in sales last year. According to GlobalData’s Pharma Intelligence Center, Rybrevant is projected to reach $3.9 billion in sales by 2030, whereas Tagrisso is expected to achieve $7.7 billion in the same year.

In the announcement of the approval, J&J’s executive vice president Jennifer Taubert stated, “Building on more than three decades of oncology innovation, we are uniquely positioned to build best-in-class treatments where survival rates have remained stagnant for years. Rybrevant plus Lazcluze establishes a new benchmark in the advanced first-line setting, and we look forward to bringing this new chemotherapy-free treatment regimen to patients.”