- Pfizer Inc. on Tuesday revealed a data monitoring committee has recommended halting a Phase 3 study of Inlyta as an adjuvant therapy for kidney cancer after a review found the drug did not help extend disease-free survival versus placebo.
- "We are disappointed by the outcome of this study as we had hoped the efficacy that Inlyta has demonstrated as a second-line treatment in patients with advanced renal cell carcinoma would carry over to patients with earlier stage disease," said Mace Rothenberg, Pfizer's chief development officer for oncology, in an April 10 statement.
- Despite the setback, combination trials testing Inlyta together with immunotherapy in first-line renal cell carcinoma (RCC) will continue, Pfizer said.
Sales of Inlyta (axitinib), a tyrosine kinase inhibitor (TKI) approved for second-line treatment of RCC in 2012, have weakened recently — falling 15% year over year in 2017. Analysts from investment bank Cowen & Co. expect that decline to continue, steadily eroding sales to below $200 million a year by 2024.
The failure of Pfizer's study, called ATLAS, closes off an opportunity to expand the drug's market and provide a commercial boost.
ATLAS tested Inlyta as an adjuvant treatment in 724 patients at high risk of RCC recurrence following surgical removal of a kidney. Yet review by an independent panel found the drug didn't show any marked improvement over placebo on the study's primary endpoint of disease-free survival.
Non-metastatic kidney cancer patients typically will have an affected kidney removed in an effort to eliminate the cancer. Some, however, relapse after surgery, and prognoses are usually poor once the cancer subsequently metastasizes.
Shutting down the trial leaves the focus for Pfizer squarely on Inlyta's potential use as a partner to immunotherapy.
Pfizer is currently running a Phase 3 study comparing a combination of Inlyta with its PD-L1 inhibitor Bavencio (avelumab) to the pharma's aging drug Sutent (sunitinib) in first-line RCC. Enrolling 830 patients, the trial will be a test of the rationale for combining TKIs with PD-L1 blockade.
Results are expected as soon as June — an event executives at the drugmaker have eagerly talked up.
"We do think that combining Inlyta with Bavencio is really a unique combination for renal cell carcinoma, and that the data reported were really impressive and ... stands out among the absolutely best seen this far," said Pfizer's head of R&D Mikael Dolsten on a call with analysts Jan. 30.
Data from a Phase 1b study presented at last year's annual meeting of the American Society of Clinical Oncology showed treatment with the pairing led to a 54% (30/55) response rate. Nine patients had to discontinue one of the drugs due to adverse events, however, and one patient died due to treatment-related myocarditis.
Merck & Co. is also conducting a late-stage study pairing Inlyta with Keytruda (pembrolizumab) in first-line RCC.
Even if Pfizer sees positive results from its combo study, the first-line RCC market looks set to become competitive. An immunotherapy combination from Bristol-Myers Squibb Co. awaits a decision on approval by the Food and Drug Administration, while Merck and Bristol-Myers are testing their respective checkpoint inhibitors in late-stage RCC studies as well.
Merck, in particular, recently inked a major deal with Japanese pharma Eisai Co. Ltd. to co-develop Keytruda together with Eisai's TKI Lenvima (lenvatinib mesylate). The FDA has already granted a Breakthrough Therapy Designation to the two drugs together in RCC.