With the FDA nodding in lung cancer, Dizal is now aiming for the best J&J medicines and succeeding where Takeda falls off
One of the most competitive targets in lung cancer is some kind of mutation that avoids many of the targeted therapies available. A drug developed by Dizal Pharmaceutical has been approved by the FDA to treat patients who exhibit this genetic signature in the disease, which makes the Shanghai-based company the first U.S. product in the United States and has the opportunity to differentiate from the therapies generated by some of the major pharmaceutical companies’ labs.
Dizal’s drug is used to treat non-small cell lung cancer (NSCLC), which carries an exon 20 insertion mutation in the EGFR gene. This genetic characteristic must be determined by the Thermo Fisher Scientific Companion diagnosis. The FDA approved both on Wednesday night. Patients with a daily medication for Dizal were approved for treatment during or after chemotherapy treatment. The drug, known in development as SunVozertinib, will be commercialized under the brand name Zegfrovy.
EGFR plays a key role in cellular processes in the body, but mutations in this protein can cause uncontrollable driving cancer cells. The best-selling EGFR inhibitor is Tagrisso from Astrazeneca, a small oral molecule. However, this blockbuster cancer drug has not yet been effective for EGFR exon 20 insertion mutations. Dizal CEO Xiao Zhangzhang learned about it personally. Prior to founding Dizal in 2017, his 20-year career at Astrazeeneca included working at Tagrisso.
Exon 20 insertion mutations originate from inserting genetic material into the EGFR gene. One way AstraZeneca is trying to give this target drug use is to use higher doses of tagrisso, Zhang said. Although testing of this method showed some activity, it also led to unacceptable toxicity. The challenge of inserting mutation into exon 20 is that it is not a mutation. Zhang said insertions can be performed in many ways, and the study revealed more than 120 mutations, each depending on the location of the gene and the size of the insertion.
“One of the biggest challenges in designing a molecule is that it is soft enough to inhibit all these different types of insertion mutations?” he was interviewed at the 2025 Annual Meeting of the American Society of Clinical Oncology in 2025. “But you also don’t want your compound to be too soft that it’s not stable enough. This is a key challenge.”
Zegfrovy was discovered and developed internally by Dizal scientists who designed small molecules targeting various EGFR mutations, not just exon 20 insertion mutations. Another key property of the drug: it is selective for mutated versions of the EGFR protein. Antibodies can only resolve the outside of their target. The problem is that the normal EGFR and mutant forms of EGFR are the same extracellular regions. Zhang said this means that antibodies aimed at the drug mutant EGFR also affect normal EGFR, causing adverse reactions elsewhere in the body.
The FDA’s decision to Zegfrovy was based on the results of the Open Label Phase 2 study to accelerate approval. Among the 85 patients’ efficacy population, the results showed an overall response rate of 46% and a response duration of 11.1 months. A confirmatory phase 3 study completed enrollment. Zhang said this global study could support the use of Zegfrovy as the first-line treatment for eligible NSCLC patients. Dizal’s goal is to file an FDA application to seek to expand drug labeling early next year.
The first drug for EGFR exon 20 insertion into mutation-driven NSCLC is Johnson & Johnson’s Rybrevant, which received second-line treatment in 2021 and accelerated approval in 2021. This bispecific antibody blocks EGFR and a second receptor called MET, both overexpressed on the NSCLC cell surface. Last year, the FDA approved Rybrevant’s frontline use in this type of cancer, turning the status of the drug into full approval.
Rybrevant is used as an intravenous infusion and can take up to five hours. Dizal is one of several pharmaceutical companies that develop more convenient oral small molecules for the goal. Takeda Pharmaceutical has received accelerated approval for oral medications with EGFR exon 20 insertion mutations for the first time, a regulatory decision proposed several months after Rybrevant’s accelerated approval. However, the drug, coming soon, continues to fail to pass its confirmatory phase 3 study. Takeda voluntarily withdraws from the market from 2023. The FDA rejected Spectrum’s oral small molecule Poziotinib in 2022.
There are other companies that develop oral small molecules for exon 20 insertion mutations. At the ASCO meeting, Cullinan Therapeutics doctrine, which plans to submit the FDA for Zipalertinib in the second half of this year. Similar to Dizal, Cullinan executives said their drug is more selective for mutated EGFR. Arrivent Biopharma achieved late clinical development through its oral small molecule Firmonertinib. Arrivent said its medications can be separated from brain penetration properties, allowing it to treat NSCLCs that have been transferred to the brain.
“There are some other things behind us [treatment of EGFR exon 20-mutated NSCLC]we are leaders. ” Zhang said.
Zhang said Zegfrovy’s oral small molecule formula has the advantages of safety and tolerance compared to Rybrevant. Even so, the FDA notes that warnings about Dizal drugs include interstitial lung disease and lung inflammation. Gastrointestinal problems; skin reactions; and eye toxicity. The drug has been commercially available in China and was approved in 2023.
As for ours. Zegfrovy’s commercialization, Zhang said his company had discussions with potential partners. He pointed out that Dizal already has commercial infrastructure in China, and commercialization strategies are different between the East and the West. In the United States, many biotech companies are single-investment products companies with the goal of exceeding the drug or being directly acquired by a large pharmaceutical company. In China, a biotech company is expected to go from discovery to commercialization. Dizal has a second commercial cancer drug in China and is a pipeline across oncology and immunology.
“We do have a commercial organization in China, but, [in the] We and Europe are gradually building our business operations as we have multiple assets and over the next few years we will be approved for three to five assets. ” Zhang said.
Illustration: Mohammed Haneefa Nizamudeen, Getty Images
