Dizal's Zegfrovy Gains FDA Approval, Challenging J&J in Rare Lung Cancer Treatment

China's Dizal Pharmaceuticals has secured its first FDA approval for Zegfrovy (sunvozertinib), an oral treatment for a rare type of non-small cell lung cancer (NSCLC). This milestone comes eight years after the company's establishment, partly by AstraZeneca, and positions Zegfrovy as a potential competitor to Johnson & Johnson's Rybrevant in the U.S. market.

FDA Approval and Treatment Landscape

The FDA granted accelerated approval to Zegfrovy for patients with EGFR exon 20 insertion mutations whose cancer has progressed after platinum-based chemotherapy. This approval makes Zegfrovy the only FDA-endorsed oral treatment for this specific indication, offering an alternative to J&J's infused Rybrevant.

Zegfrovy's approval is supported by the WU-KONG1B trial results, which demonstrated a 46% tumor shrinkage rate and an 11.1-month median duration of response. These figures compare favorably to Rybrevant's 40% objective response rate (ORR) and identical 11.1-month median duration of response from its 2021 approval data.

Dr. Xiaolin Zhang, CEO of Dizal, emphasized Zegfrovy's potential, stating, "(Zegfrovy) offers a more effective treatment option with enhanced safety and ease of administration for NSCLC patients with EGFR exon 20 insertions."

Market Implications and Clinical Significance

The approval of Zegfrovy introduces a new player in the treatment of EGFR exon 20 insertion mutations, which affect approximately 2% of NSCLC patients. This genetic type represents the third most common EGFR mutation and has been particularly challenging to treat due to its unique characteristics.

Dr. Mengzhao Wang, principal investigator of the WU-KONG1B study, highlighted the difficulties in treating this type of NSCLC, noting its "unique spatial conformation, diverse mutation subtypes, and high heterogeneity," which have historically led to poor prognosis and limited treatment options.

Zegfrovy's once-daily oral dosing may offer advantages in terms of administration convenience and patient adherence. Dr. Pasi Jänne of Harvard Medical School and lead principal investigator of the WU-KONG1B trial, emphasized this point, stating, "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."

Future Prospects and Ongoing Research

Dizal is currently conducting a multinational phase 3 trial, WU-KONG28, which will evaluate Zegfrovy against chemotherapy in treatment-naïve patients across 16 countries. Preliminary data presented at the 2023 European Society for Medical Oncology (ESMO) conference showed promising results for Zegfrovy as a first-line treatment, with a 79% ORR and a median progression-free survival of 12.4 months.

The success of this ongoing research will be crucial in determining Zegfrovy's long-term position in the market, especially given the cautionary tale of Takeda's Exkivity. Despite receiving accelerated FDA approval in 2021, Exkivity was withdrawn from the U.S. market two years later after failing to outperform chemotherapy in a confirmatory trial.