Dizal set to bring lung cancer drug Zegfrovy to US

China's Dizal Pharmaceutical has claimed FDA approval for its selective EGFR inhibitor sunvozertinib as a treatment for non–small-cell lung cancer (NSCLC) with EGFR exon 20 insertions, two years after getting a green light for the drug in its home market.

Dizal will market sunvozertinib in the US under the Zegfrovy brand name, entering a market for EGFR inhibitors currently dominated by AstraZeneca's Tagrisso (osimertinib) but currently being shaken up by new entrants like Johnson & Johnson's infused bispecific antibody Rybrevant (amivantamab).

At the moment, Rybrevant is the only drug in the class approved for NSCLC patients with exon 20 mutations, getting FDA approval in 2021 as second-line therapy after platinum-based chemotherapy. Tyrosine kinase inhibitor-based EGFR drugs, including Tagrisso, have struggled to show efficacy against this type and are used mainly to treat tumours with exon 19 and 21 mutations.

NSCLC driven by exon 20 mutations tend to carry a worse prognosis and shorter survival times compared with lung cancer driven by other, more common EGFR mutations, typically surviving less than 18 months after a diagnosis.

One literature review, focusing on Europe, estimated that the overall frequency of exon 20 insertions in a general NSCLC population was up to around 2% of cases, and up to a third of EGFR-positive NSCLC.

Alongside Zegfrovy, the FDA has also approved a companion diagnostic for exon 20 insertions, Life Technologies' Oncomine Dx Express test, that can be used to identify patients eligible for treatment with Dizal's drug.

The approval is based on data from part B of the phase 1/2 WU-KONG1 study reported at ASCO 2024, which enrolled patients after chemotherapy, with or without Rybrevant. In a boost for Dizal, the FDA approval for Zegfrovy does not stipulate prior Rybrevant treatment.

The drug achieved an overall response rate (ORR) of 46% in the trial with a duration of response of 11.1 months, said the FDA in a statement on the decision.

Lead investigator Pasi Jänne of Dana-Farber Cancer Institute said that the drug is "the world's only approved targeted oral therapy" for this type of NSCLC and the US approval "represents a meaningful milestone in addressing the long-standing unmet medical needs of this underserved patient population."

The regulator said the recommended dose of the drug is 200mg orally, once daily with food, until disease progression or unacceptable toxicity.

Dizal is also seeking to move Zegfrovy into the first-line exon 20-positive NSCLC setting, where Rybrevant is also approved, via the WU-KONG28 trial, which has completed enrolment across 16 countries.

The question now is when Zegfrovy will be available in the US, and whether Dizal will market it there or seek a commercial partner.