Eight years after it was established partly by AstraZeneca, Dizal Pharmaceuticals has gained its first FDA approval, winning an accelerated nod for Zegfrovy (sunvozertinib) to become the only U.S.-endorsed oral treatment for those with a rare type of non-small cell lung cancer (NSCLC).

Patients in the U.S. with EGFR exon 20 insertion mutations whose cancer has progressed after platinum-based chemotherapy are now eligible for Zegfrovy.

The blessing comes 16 months after the FDA signed off on Johnson & Johnson’s infused Rybrevant in combination with chemotherapy as a first-line treatment in the indication. While Rybrevant is an EGFR-MET bispecific antibody, Zegfrovy is a first-in-class selective EGFR tyrosine kinase inhibitor (TKI).

“(Zegfrovy) offers a more effective treatment option with enhanced safety and ease of administration for NSCLC patients with EGFR exon 20 insertions,” Dizal CEO Xiaolin Zhang, Ph.D., said in a release.

Zhang, who served at AstraZeneca for 20 years before taking the reins at Dizal, told Fierce Pharma last year that he was in discussions with multiple drugmakers who were interested in partnering with the Shanghai-based company on Zagfrovy. Dizal already commercializes the drug in China, where it was approved in August of 2023.

Since the FDA signed off on Zegfrovy last week, Dizal’s share price has increased by 10%.

Dizal will try to succeed where another oral EGFR inhibitor failed in the indication. Takeda’s Exkivity, which received an accelerated FDA approval for second-line use in 2021, was withdrawn from the U.S. market two years later after it failed to beat out chemotherapy in a confirmatory trial.

Supporting the FDA approval of Zagfrovy is the WU-KONG1B trial, which showed the treatment shrunk tumors in 46% of patients and provided an 11.1-month median duration of response.

These figures compare to a 40% objective response rate (ORR) and an 11.1-month median duration response, which backed the accelerated nod for Rybrevant in 2021.  Meanwhile, the trial supporting conditional approval of Exkivity showed a 28% ORR.

Additionally, in WU-KONG1B, Zagfrovy showed an anti-tumor effect regardless of prior treatment with Rybrevant. The WU-KONG1B trial enrolled patients in Asia, Europe, North America, and South America.

“Findings from WU-KONG1B have demonstrated Zegfrovy's significant therapeutic effects with consistent efficacy across both Asian and non-Asian patient populations,” Pasi Jänne, M.D., Ph.D., of Harvard Medical School and the lead principal investigator, said in the release. “Its convenient once-daily oral dosing substantially improves administration convenience and patient adherence, which is an increasingly critical factor as lung cancer care shifts toward chronic disease management.”

Along with the approval, the FDA simultaneously signed off on Thermo Fisher’s Oncomine Dx Express Test as a companion diagnostic to identify patients with EGFR Exon 20 insertions.

Roughly 2% of NSCLC patients have the genetic type, though it is the third most common type of EGFR mutation.

Treating this type of NSCLC is “particularly challenging” because of its “unique spatial conformation, diverse mutation subtypes, and high heterogeneity,” according to Mengzhao Wang, M.D., Ph.D., the principal investigator of the WU-KONG1B study. “As a result, patients face a poor prognosis and limited treatment options.”

As for the progression of Zagfrovy, much will depend on its multinational phase 3 WU-KONG28 trial. Dizal has completed enrollment in the study which will evaluate Zagfrovy versus chemotherapy in treatment-naïve patients in 16 countries.

At the 2023 European Society for Medical Oncology (ESMO) conference, Dizal reported that Zegfrovy as a solo treatment in the first-line setting achieved an ORR of 79% and a median progression-free survival of 12.4 months.