After a prior rejection, Astellas can head into the weekend celebrating a class-first FDA approval for its new gastric cancer med Vyloy.
The FDA on Friday gave Vyloy (zolbetuximab) the thumbs-up as a first-line treatment for adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction adenocarcinoma whose tumors are CLDN18.2 positive.
With the green light, Vyloy becomes the first U.S.-approved anti-CLDN18.2 drug. The transmembrane protein, also known as Claudin-18.2, has become a red-hot target in the oncology field, ginning up interest from the likes of AstraZeneca, Leap Therapeutics, Legend, Moderna and other companies.
Friday’s approval specifically covers Vyloy in combination with fluoropyrimidine- and platinum-containing chemotherapy. Patients must have the CLDN18.2 positivity of their tumors confirmed through testing, and, to that end, the FDA has simultaneously approved a new companion diagnostic from Ventana Medical Systems and Roche.
The FDA based its approval on positive results from two phase 3 trials dubbed SPOTLIGHT and GLOW.
In the 565-patient SPOTLIGHT study, patients on Vyloy plus chemotherapy achieved median progression-free-survival (PFS) of 10.6 months, compared with 8.7 months in the group that received placebo plus chemo. Median overall survival (OS) clocked in at 18.2 months for patients on Vyloy, compared to 15.5 months in the trial’s control arm.
In GLOW, which enrolled 507 patients, Zyloy helped patients achieve a median PFS of 8.2 months over the 6.8 months observed in the placebo/chemotherapy cohort. Median OS was 14.4 months and 12.2 months, respectively.
Vyloy wasn’t due for an FDA decision until Nov. 9. While the regulator previously granted the antibody a priority review tag in July 2023, Astellas’ approval timeline was derailed following the receipt of a complete response letter in January.
The FDA rejected the drug over unresolved deficiencies uncovered during a pre-license inspection of a third-party manufacturing facility, Astellas explained at the time. The FDA did not raise any concerns about Vyloy’s clinical data package.
In late May, Astellas said the FDA had accepted its resubmission for the drug.
Astellas first got its hands on Vyloy through its $1.4 billion buyout of Ganymed Pharmaceuticals in 2016. Despite the regulatory stumble in the U.S., Vyloy has already clinched several other approvals abroad, including in the company’s home country of Japan, where Vyloy passed muster with the nation’s Ministry of Health, Labour and Welfare in March.
At the time, Astellas touted Vyloy as the first CLDN18.2-targeted therapy to win approval anywhere. Astellas’ med has also snagged regulatory endorsements in Europe and the U.K.
While Astellas currently has the anti-CLDN18.2 space all to itself, several other companies have candidates working their way through the clinic.
Last year, AstraZeneca paid KYM Biosciences $63 million upfront for the global rights to a CLDN18.2-targeting antibody-drug conjugate, doubling down after entering the space through a $25 million pact with Harbour BioMed in 2022.
Meanwhile, Merck & Co. recently reduced its presence in the field after returning global rights to Kelun-Biotech’s CLDN18.2-directed ADC SKB315. Despite Merck’s action, Kelun said in August that its med had shown positive efficacy and acceptable safety in CLDN18.2-expressing gastric cancer during early-stage testing.