FDA urges Dizal to seek fast-track approval for lung cancer drug despite J&J's Rybrevant approval

The FDA has confirmed an accelerated approval pathway for Dizal Pharma's sunvozertinib, a treatment aimed at non-small cell lung cancer (NSCLC) patients with EGFR exon 20 insertion mutations who have already undergone treatment. This comes after the FDA granted full approval to Johnson & Johnson’s (J&J) Rybrevant for the same condition in March. Despite this, the FDA remains open to additional treatments, indicating a continued need for alternative therapies.

Dizal Pharma, an AstraZeneca spinout, has developed sunvozertinib, an EGFR tyrosine kinase inhibitor. The drug received approval in China in August for use in pretreated NSCLC with EGFR exon 20 insertion mutations. Following a successful global trial and a positive pre-NDA meeting with the FDA, Dizal is preparing to file for accelerated approval in the U.S. The FDA has also granted sunvozertinib breakthrough therapy designation as a frontline treatment.

According to Dizal CEO Xiaolin Zhang, Ph.D., the FDA recognizes the necessity for diverse treatment options for this disease. While the FDA has previously rejected accelerated approval applications when a full approval exists, the difference in drug mechanisms between sunvozertinib and Rybrevant could influence the agency's decision. Unlike Rybrevant, which is an EGFR-MET bispecific antibody, sunvozertinib operates differently, potentially broadening the range of available therapies.

Dizal is actively seeking partnerships with larger pharmaceutical companies to enhance the commercialization of sunvozertinib. Many potential partners are keenly watching the results from the global WU-KONG1B trial, which were presented at the ASCO 2024 meeting. This trial is pivotal to sunvozertinib’s potential market success, particularly in the first-line treatment setting.

Sunvozertinib has shown promising results in the WU-KONG1B trial, which included a significant portion of non-Asian patients. The trial reported a best overall response rate (ORR) of 53.3% and a confirmed ORR of 44.9% among 107 patients treated with the recommended dose of 300mg. Importantly, the drug demonstrated effectiveness regardless of prior treatment with Rybrevant, with best ORRs of 50% for those previously treated with Rybrevant and 53.8% for those who were not.

However, Dizal must wait for at least six months of follow-up data for the last responder before filing with the FDA. This additional data is expected by late June. For context, Rybrevant’s accelerated approval in 2021 was based on a 40% ORR and a median response duration of 11.1 months. Sunvozertinib’s data appears more favorable when compared to Takeda’s Exkivity, which had a 28% ORR and is being withdrawn from the market due to poor phase 3 trial results.

Sunvozertinib is designed to target a broad range of EGFR exon 20 insertions and some wild-type EGFR, offering flexibility that other treatments might lack. To secure accelerated approval, a confirmatory trial is required. The phase 3 WU-KONG28 trial, which is already 70% enrolled, could fulfill this requirement. This trial compares sunvozertinib monotherapy to standard platinum-based chemotherapy in first-line EGFR exon 20-mutated NSCLC.

While J&J’s Rybrevant has succeeded in combination with chemotherapy, Dizal believes a monotherapy approach with sunvozertinib is preferable for newly diagnosed patients due to quality of life considerations. Early-phase data showed sunvozertinib monotherapy had a median progression-free survival of 12.4 months, comparing favorably to Rybrevant-plus-chemo’s 11.4 months.

J&J is also targeting more common EGFR mutations, an area dominated by AstraZeneca's Tagrisso. Dizal, understanding Tagrisso's strengths, aims to focus on second-line treatments following Tagrisso’s failure. Potential combinations include sunvozertinib with chemotherapy or Dizal’s JAK1 inhibitor golidocitinib, which has been approved in China for peripheral T-cell lymphoma, and with DZD6008, an EGFR inhibitor designed for post-Tagrisso treatment.