One of many extra aggressive targets in lung most cancers is a sure mutation that has eluded many out there focused therapies. A drug developed by Dizal Pharmaceutical has obtained FDA approval for treating sufferers whose illness displays this genetic signature, giving the Shanghai-based firm its first U.S. product together with the chance to indicate differentiation from therapies generated by the labs of some massive pharmaceutical corporations.
Dizal’s drug was developed for treating non-small cell lung most cancers (NSCLC) that carries an exon 20 insertion mutation within the EGFR gene. That genetic signature should be recognized by a Thermo Fisher Scientific companion diagnostic. The FDA authorised each late Wednesday. Remedy with Dizal’s once-daily capsule is authorised for sufferers whose illness has progressed throughout or after remedy with chemotherapy. The drug, recognized in growth as sunvozertinib, can be commercialized beneath the model title Zegfrovy.
EGFR performs a key function in mobile processes within the physique, however mutations to this protein can result in the uncontrolled proliferation of cells that drive most cancers. The highest-selling EGFR inhibitor is AstraZeneca’s Tagrisso, an oral small molecule. However this blockbuster most cancers drug has not been efficient towards EGFR exon 20 insertion mutations. Dizal CEO Xiaolin Zhang is aware of firsthand. Earlier than founding Dizal in 2017, his 20-year profession at AstraZeneca included engaged on Tagrisso.
Exon 20 insertion mutations stem from the insertion of genetic materials into the EGFR gene. Zhang mentioned a technique AstraZeneca tried to drug this goal was to make use of larger doses of Tagrisso. Whereas checks of this strategy confirmed some exercise, it additionally led to unacceptable toxicity. The problem for drugging the exon 20 insertion mutation is that it’s not a single mutation. Zhang mentioned the insertions can occur in some ways and analysis has revealed greater than 120 sorts of this mutation, every one relying on the place of the gene and the scale of the insertion.
“One of many largest challenges designing a molecule is that’s it versatile sufficient to suit, to have the ability to inhibit all these totally different sort of insertional mutations?” he mentioned in an interview on the 2025 annual assembly of the American Society of Scientific Oncology. “But additionally, you don’t need your compound too floppy that it isn’t secure sufficient. That’s the key problem.”
Zegfrovy was internally found and developed by Dizal scientists, who designed the small molecule to focus on a variety of EGFR mutations — not simply exon 20 insertion mutations. One other key property of the drug: It’s selective to mutant variations of EGFR protein. An antibody can solely addresses the surface of its goal. The issue is that the extracellular area of EGFR is identical for each regular EGFR and mutant kinds. Meaning an antibody supposed to drug mutant EGFR may also have an effect on regular EGFR, sparking adversarial results elsewhere within the physique, Zhang mentioned.
The FDA resolution for Zegfrovy is an accelerated approval based mostly on outcomes from an open-label Part 2 examine. Within the efficacy inhabitants of 85 sufferers, outcomes confirmed the general response price was 46% and the length of response was 11.1 months. A confirmatory Part 3 examine has accomplished enrollment. Zhang mentioned this international examine may assist use of Zegfrovy as a first-line remedy for eligible NSCLC sufferers. Dizal goals to file an FDA utility searching for to develop the drug’s label early subsequent 12 months.
The primary drug for NSCLC pushed by EGFR exon 20 insertion mutations was Johnson & Johnson’s Rybrevant, which obtained accelerated approval in 2021 as a second-line remedy. This bispecific antibody blocks EGFR and a second receptor known as MET, each of that are overexpressed on the floor of floor of NSCLC cells. Final 12 months, the FDA authorised Rybrevant for first-line use in such a most cancers, changing the drug’s standing to full approval.
Rybrevant is run as an intravenous infusion that may take as much as 5 hours. Dizal is one in every of a number of drug corporations working to develop extra handy oral small molecules for the goal. Takeda Pharmaceutical was first to safe accelerated FDA approval for an oral drug for EGFR exon 20 insertion mutations, a regulatory resolution that got here months after Rybrevant’s accelerated approval. However this drug, Exkivity, went on to fail its confirmatory Part 3 examine. Takeda voluntarily withdrew Exkivity from the market in 2023. Spectrum Prescribed drugs didn’t even get that far. The FDA turned down Spectrum’s oral small molecule, poziotinib, in 2022.
There are different corporations growing oral small molecules for exon 20 insertion mutations. Throughout the ASCO assembly, Cullinan Therapeutics mentioned it plans an FDA submission within the second half of this 12 months for zipalertinib. Much like Dizal, Cullinan executives say their drug is extra selective to mutant EGFR. ArriVent BioPharma has reached late-stage scientific growth with its oral small molecule, firmonertinib. ArriVent has mentioned its drug can stand aside with brain-penetrating properties that allow it to deal with NSCLC that has metastasized to the mind.
“There are just a few others behind us, however for second-line [treatment of EGFR exon 20-mutated NSCLC], we’re the chief,” Zhang mentioned.
In comparison with Rybrevant, Zhang mentioned the oral small molecule formulation of Zegfrovy provides it security and tolerability benefits. Even so, the FDA famous that warnings for the Dizal drug embody interstitial lung illness and lung irritation; gastrointestinal issues; pores and skin reactions; and eye toxicity. The drug is already commercially out there in China, the place it was authorised in 2023.
As for U.S .commercialization of Zegfrovy, Zhang mentioned his firm has had discussions with potential companions. He famous that Dizal already has industrial infrastructure in China, and commercialization methods differ between the East and West. Within the U.S., many biotech corporations are single-asset corporations whose purpose is to out-license the drug or be acquired outright by an enormous pharmaceutical firm. In China, the expectation is {that a} biotech firm goes from discovery to commercialization. Dizal has a second commercialized most cancers drug in China and a pipeline spanning oncology and immunology.
“We do have a industrial group in China doing very properly however, [in the] U.S. and Europe, regularly we’re going to construct our industrial presence as a result of now we have a number of property and within the subsequent few years we’re going to have three to 5 property authorised,” Zhang mentioned.
Illustration: Mohammed Haneefa Nizamudeen, Getty Pictures
