UPDATED: J&J beats Tagrisso and Takeda to the punch in key NSCLC subset, picking up new FDA approval
Looking to outflank AstraZeneca’s best-selling drug in a non-small cell lung cancer niche, J&J scored an important approval Friday afternoon.
Regulators gave the thumbs-up to Janssen’s amivantamab for the treatment of metastatic NSCLC with EGFR exon 20 insertion mutations, the FDA announced Friday. It’s the first drug approved to treat such patients, with J&J planting a stake in a part of the EGFR mutation arena where its competitors have struggled to gain a foothold.
The drug, whose approval comes after J&J jumped straight from a Phase I study to a BLA priority review, will be branded as Rybrevant. In an emailed statement to Endpoints News, J&J declined to comment on specific pricing for the drug, saying only that it would “reflect its incremental value” in NSCLC outcomes for this population and be “comparable to other infused oncology medicines.”
While lung cancer is the most common form of cancer and is the leading cause of worldwide cancer deaths, patients with EGFR exon 20 insertion mutations had been excluded from taking previously approved drugs — only about 2% to 3% of NSCLC patients have these mutations, the FDA said. That list includes AstraZeneca’s blockbuster Tagrisso, which raked in more than $4 billion last year.
Tagrisso is only OK’ed for exon 19 deletions or exon 21 L858R mutations, or patients with EGFR mutations who had undergone tumor resection and optional, standard postoperative adjuvant chemotherapy.
One of the primary reasons past medicines haven’t worked in this new class is the drugs don’t bind all that well to the target, J&J investigator Joshua Sabari told Endpoints ahead of WCLC in January. But Rybrevant is an EGFR/MET bispecific that binds outside of the cell, which J&J says better inhibits tumor growth among the exon 20 insertion mutation population.
Friday’s approval was based on those WCLC Phase I data, looking at 81 patients whose NSCLC had progressed on or after platinum chemo. Within the study, 32 individuals saw at least a partial response, good for an ORR of 39.5%. The responses were also shown to last with the drug prompting a median duration of 11.1 months, and 20 of the 32 patients demonstrated a response of at least six months.
J&J likely won’t be satisfied with just this indication given the competition from Tagrisso and another program from Takeda called mobocertinib.
Researchers are continuing to study how Rybrevant can affect advanced NSCLC patients when used in combination with an in-house TKI called lazertinib, pitting this combo head-to-head with Tagrisso in a Phase III trial in previously untreated patients. There’s also another trial for the Rybrevant/lazertinib duo involving patients who have taken both Tagrisso and chemotherapy but still progressed.
The Takeda candidate presented data back in January showing a similar overall response rate of 35%, but high rates of severe GI side effects could temper expectations. Earlier this week at ASCO, however, mobocertinib posted a median OS of 24 months at a 14-month follow-up.