FDA Changes the Game: First Cancer Drug Approval Based on Biomarker

The U.S. Food and Drug Administration has issued its first drug approval to a treatment for patients with a specific genetic biomarker, rather than based on an initial tumor location, such as breast cancer. On May 23, the agency granted an accelerated approval to Merck’s Keytruda (pembrolizumab) for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) genetic markers, where the tumors have progressed following prior therapy or there are no satisfactory treatment alternatives.  MSI-H and dMMR are abnormalities that affect DNA repair. They are common in colorectal cancer (affecting about 5% of metastatic disease), endometrial, and gastrointestinal cancers, and occur less frequently in breast, prostate, bladder, thyroid and other cancers. Patients with MSI-H or dMMR tend to respond poorly to chemotherapy, so this new biomarker-based approval may prove to be a significant gain for those patients.

 

The accelerated approval was based on the results of 5 open-label, Phase 1/2 clinical trials in 149 patients with 15 different tumor types. Complete or partial responses were seen in 39.6% of the treated patients, with 78% of those experiencing a response duration of six months or more.

 

Keytruda has been making significant regulatory gains in recent weeks, also gaining approval for use in bladder cancer in May, and on May 24, an accelerated review for the treatment of stomach cancer. We expect to hear a lot more about this drug at ASCO, where 16 different abstracts have been accepted.

 

This biomarker-based approval has multiple implications for the future of cancer care. As the first truly tumor-agonistic approval for an oncology drug in major cancer indications, this development could prove to be transformative. However, it is still early.  At present, the approval only affects the use of Keytruda in late-stage cancer patients, after other treatments have failed. The data supporting the approval — which remains conditional — needs to be matured; the five trials supporting FDA’s decision were in small numbers of patients and were open-label. Moreover, only colorectal, endometrial and GI cancers have significant numbers of patients who fit the profile for the approved label. Will this change as more data is acquired or will the target patient population remain limited?

 

With respect to the marketplace, we wonder to what extent a biomarker-based approval can drive differentiation — and for how long. A variety of competitors have MSI-focused trials, although most are focused on one or a very few tumor types and it does not appear — for now — that the tumor agnostic approach is one where other companies have universally jumped in.

 

With respect to the clinic and insurers, the approval could help push further adoption — and reimbursement — for broad-based genetic testing in cancer. Tests that steer patients to better results from costly therapies are increasingly likely to be viewed as a positive tool by insurers to help limit such drugs to those who have the likeliest probability of a positive response.