Johnson & Johnson continues to grow its oncology franchise with a new FDA approval that opens the lung cancer drug Rybrevant to treating certain newly diagnosed patients.
Friday’s approval allows Rybrevant to be used alongside the chemotherapies carboplatin and pemetrexed as a first-line treatment for advanced non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations.
Simultaneously, Rybrevant’s original accelerated approval as a single agent for chemo-pretreated tumors has been converted to a full approval, the agency said.
Rybrevant’s first-line nod comes five months after Takeda announced a voluntary market withdrawal of its rival EGFR exon 20 NSCLC drug, Exkivity, which failed as a monotherapy in its own first-line trial. Before their divergent phase 3 reports, the two drugs were sharing the second-line market roughly 50-50.
The FDA considered positive data from the phase 3 PAPILLON trial in granting Rybrevant the first-line indication. Compared with chemo alone, the combination of Rybrevant and chemo cut the risk of progression or death by 60% in patients with NSCLC with EGFR exon 20 insertion mutations. Patients who received the J&J bispecific went 11.4 months without their disease worsening, compared with 6.7 months for those in the control arm.
While patient survival data remained immature—with only 44% of deaths required for the final overall survival analysis—“no trend towards a detriment was observed,” the FDA noted in Rybrevant’s new label.
Previously, with 33% data maturity, the Rybrevant-chemo regimen showed a trend toward a 33% reduction in the risk of death. Nearly half of patients in the chemo-alone arm later went on to receive single-agent Rybrevant following disease progression.
Although Takeda’s Exkivity is out of the picture, other small-molecule agents targeting EGFR exon 20 NSCLC are biding their time to challenge J&J’s antibody drug.
ArriVent BioPharma, which recently staged an upsized IPO, is working on a pan-EGFR mutant inhibitor called furmonertinib. The drug, licensed to ArriVent by Allist Pharma, was approved in China originally for second-line treatment of NSCLC with certain EGFR mutations; it moved into the first line in 2022. Following a similar development strategy as Takeda’s approach, Arrivent is currently running the phase 3 FURVENT trial testing furmonertinib monotherapy against chemo in previously untreated NSCLC with EGFR exon 20 insertion mutations.
Meanwhile, AstraZeneca spinout Dizal Pharmaceutical is also looking to bring its China-approved sunvozertinib to EGFR exon 20 NSCLC in the U.S. market. Dizal also has a phase 3 trial evaluating the drug by itself against chemo in the first-line setting, and the company recently told Fierce Biotech that it was talking to Big Pharma companies about a potential partnership.
EGFR exon 20 mutations only represent a small market, with an estimated frequency of about 0.1% to 4% of all NSCLC cases.
For Rybrevant, the most important indication would be first-line NSCLC with the more prevalent exon 19 or exon 21 abnormalities, where AstraZeneca’s blockbuster Tagrisso is king. There, J&J recently earned FDA priority review for its application of Rybrevant and its Yuhan-partnered lazertinib based on a head-to-head win against Tagrisso in the phase 3 MARIPOSA trial.
If approved, the Rybrevant-lazertinib regimen would need to challenge both Tagrisso monotherapy and a Tagrisso-chemo combination.
During a recent investor event, J&J laid out an ambition to snag about half of first-line patients in EGFR-mutant NSCLC. J&J believes the Rybrevant-lazertinib regimen could reach over $5 billion in peak sales. In 2023, AZ’s Tagrisso generated $5.9 billion in sales, good for 9% growth at constant exchange rates.