Hutchmed, the original developer of Takeda’s Fruzaqla, has decided not to pursue an approval for the VEGFR inhibitor in stomach cancer for now in its home country.
After an internal review and discussions with local authorities, Hutchmed has voluntarily withdrawn its application for fruquinitib in combination with chemotherapy as a second-line treatment for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma in China, the company said Friday. Hutchmed co-markets the drug with Eli Lilly in China under the brand name Elunate, while Takeda holds ex-China rights.
Hutchmed made the decision after realizing that an approval is unlikely at this time. The company said it will “evaluate a new route forward.”
The phase 3 FRUTIGA trial that Hutchmed used for the submission was considered positive given that it met one of its dual primary endpoints. But Chinese authorities still took issue with Elunate’s performance on the other primary endpoint of overall survival.
The China-only trial showed that, among patients who had progressed on first-line chemo, Elunate plus paclitaxel reduced the risk of progression or death by 43% compared with paclitaxel alone. Patients in the combo group went a median 5.6 months without progression, versus 2.7 months for the control group.
But when it came to overall survival, Elunate showed only a mere 4% advantage, which was not statistically significant. Perhaps more concerning is that starting from about 18 months into treatment, the survival curves showed that patients in the control group were more likely to be alive than the Elunate takers.
Following conversations with drug reviewers and external committee members for China’s National Medical Products Administration, Hutchmed noted that the survival results could not support an approval.
“Whilst disappointed by this outcome, we remain optimistic about the utility of fruquintinib in the treatment of gastric cancer,” Hutchmed CEO and chief scientific officer, Weiguo Su, Ph.D., said in a statement Friday. “The data set from FRUTIGA demonstrates that fruquintinib plus paclitaxel could offer a promising new treatment option to certain patients in future and we are driven to investigate this possibility thoroughly.”
China is a large market for gastric cancer, making up about 40% of the world’s new diagnoses.
In the meantime, patients who’ve received only chemo are perhaps no longer the optimal population to evaluate a second-line stomach cancer drug. PD-1 inhibitors’ combinations with chemo have emerged as a new standard for the first-line treatment of some stomach cancer patients.
Still, the FDA is putting the microscope on PD-1 drugs’ use in first-line stomach cancer. The U.S. agency is gathering an advisory committee meeting to discuss whether certain meds should be restricted based on the cancer’s PD-L1 expression levels. Existing approvals for Bristol Myers Squibb’s Opdivo and Merck & Co.’s Keytruda in HER2-negative gastric and GEJ cancers cover a broad population regardless of patients' PD-L1 expression status.
Outside of China, Fruzaqla was approved by the FDA in November 2023 and by the European Commission in June 2024 as a monotherapy for previously treated colorectal cancer. Takeda currently doesn’t have any other phase 3 trials listed for Fruzaqla in its pipeline.
In the first half of 2024, ex-China sales of Fruzaqla reached $130.5 million, and China sales of Elunate, booked by Lilly, were $61 million, according to Hutchmed.
In China, Hutchmed has further partnered with Innovent Biologics on the PD-1 inhibitor Tyvyt, which boasts its own Lilly partnership. An application for Elunate and Tyvyt in endometrial cancer was accepted by Chinese authorities with a priority review in April. A phase 3 trial testing the combo in kidney cancer has been fully enrolled.