J&J Scores First-Line Approval for Rybrevant Combination in Lung Cancer with EGFR Exon 20 Mutations

1. The FDA has granted Johnson & Johnson's Rybrevant (amivantamab-vmjw) approval for first-line treatment of patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations when combined with carboplatin-pemetrexed chemotherapy.
2. This approval is based on data from the Phase 3 PAPILLON clinical trial, which demonstrated a 61% reduction in the risk of disease progression or death compared to chemotherapy alone.
3. The combination regimen also showed improved objective response rate (ORR) and progression-free survival (PFS).
4. Rybrevant's original accelerated approval as a single agent for chemo-pretreated tumors has been converted to a full approval.
5. The National Comprehensive Cancer Network (NCCN) updated its clinical practice guidelines to include Rybrevant plus chemotherapy as a first-line treatment option for patients with NSCLC and EGFR exon 20 insertion mutations.
6. Rybrevant's first-line nod comes after Takeda's voluntary market withdrawal of its rival EGFR exon 20 NSCLC drug, Exkivity, which failed as a monotherapy in its own first-line trial.
7. Rybrevant's first-line indication is significant as EGFR exon 20 mutations represent a small market, with an estimated frequency of about 0.1% to 4% of all NSCLC cases.
8. J&J aims to capture about half of first-line patients in EGFR-mutant NSCLC and believes the Rybrevant-lazertinib regimen could reach over $5 billion in peak sales.