Johnson & Johnson tacks on another NSCLC approval in pursuit of AstraZeneca's Tagrisso

Approvals are coming fast and furious for Johnson & Johnson’s Rybrevant as it is lining up to challenge the dominance of AstraZeneca’s Tagrisso in non-small cell lung cancer (NSCLC).

Rybrevant has earned its third FDA nod in the last seven months, each covering a new indication. The U.S. regulator has signed off on Rybrevant plus standard-of-care chemotherapy (carboplatin and pemetrexed) to treat patients with locally advanced or metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 19 deletions or L858R substitution mutations who have had disease progression with an EGFR tyrosine kinase inhibitor (TKI).

Rybrevant plus chemo is the first targeted regimen to cut the risk of disease progression by more than half in second-line EGFR-mutated advanced lung cancer, J&J said.

The endorsement comes a month after J&J’s combo of Rybrevant and new, Yuhan-partnered TKI, Lazcluze, got a thumbs up for patients with newly diagnosed EGFR-mutated advanced NSCLC with one of the two common EGFR mutations at exon 19 or exon 21. That nod was backed by a phase 3 trial which showed that the combo reduced the risk of disease progression or death by 30% compared to Tagrisso as a first-line treatment.

In March, the FDA blessed Rybrevant plus chemotherapy as a first-line treatment for NSCLC with EGFR exon 20 insertion mutations. That approval came after a study showed the combo cut the risk of progression or death by 60% over standard of care chemo. 

The most recent FDA endorsement is based on results from the phase 3 MARIPOSA-2 study which showed that Rybrevant plus chemotherapy reduced the risk of disease progression or death by 52% over chemotherapy alone in patients who had shown disease progression on or after use of Tagrisso.

Patients in the study survived without disease progression for a median duration of 6.3 months on the combo versus 4.2 months for chemo alone. Additionally, the overall response rate for those on the combo was 53% compared to 29% for the chemo group.

“Rybrevant plus chemotherapy may address the most common mechanisms of treatment resistance to third generation EGFR TKIs, such as osimertinib (Tagrisso), in the first line,” Martin Dietrich, M.D., Ph.D., an oncologist at the Cancer Care Centers of Brevard, said in a release.

The advancement of Rybrevant is positive news as the five-year survival rate is less than 20 percent for all people with advanced EGFR-mutated NSCLC. In the U.S. about 30,000 are diagnosed annually with EGFR-mutated NSCLC, J&J said.

With the battery of approvals, Rybrevant is poised to begin to challenge Tagrisso, which generated sales of $5.8 billion in 2023.