- An experimental lymphoma drug from MEI Pharma and Kyowa Kirin must undergo further testing before the Food and Drug Administration will review it for approval, the companies said Thursday. They had aimed to win an accelerated FDA clearance for the drug, called zandelisib, based on Phase 2 data showing the drug reduced or eliminated signs of cancer.
- The decision comes as FDA reviews its accelerated approval program, which is also under increasing outside scrutiny, including from Congress. Meanwhile, the FDA is also investigating another drug in zandelisib's class, TG Therapeutics' Ukoniq, over an apparent increased risk of death, and has asked outside experts to evaluate the drug class more broadly at a meeting scheduled for next month.
- MEI and Kyowa Kirin have already begun a Phase 3 trial of zandelisib in combination with Rituxan in two types of lymphoma, but data may not be available for several years. MEI shares dropped by nearly 60% in Friday morning trading.
A decade ago, developers thought drugs that work like zandelisib might be one of the next big classes of cancer medicines. Drugs of this type block certain enzymes from a family called PI3K, which are involved in cell growth and differentiation. They are also oral treatments, offering convenience versus chemotherapy or the biologic drugs that serve as the backbone of many cancer regimens.
However, many have failed in clinical testing, in part due to side effects, while the ones that won approval have struggled commercially. The first to reach the U.S. market was Gilead's Zydelig in 2014, which seven years later earned the company just $62 million in sales, a drop of $10 million versus 2020. Other cancer drugs approved around the same time as Zydelig, such as the immunotherapies Keytruda and Opdivo, have thrived commercially and become standard treatments for a wide range of cancer types.
The FDA's decision to call for a Phase 3 trial signals the agency's concerns regarding PI3K inhibitors as well as its heightened focus on accelerated approvals. In a Phase 2 trial with no active drug as a comparator, 70% of patients with follicular lymphoma responded to treatment, including 35% who experienced complete remissions, according to data released by the companies via press release.
In the past, similar data has been sufficient to win an accelerated approval. But the FDA is now facing questions from lawmakers about its use of that regulatory pathway, triggered in part by its accelerated approval of Biogen's Alzheimer's disease drug Aduhelm. Even before that controversial decision, top FDA officials were reviewing the status of numerous cancer accelerated approvals, some of which have since been withdrawn.
The delay could force MEI to make some difficult strategic decisions. "Major concerns are now on multi-year delay and [the company] having sufficient funds to steer through this setback," Jefferies analyst Chris Howerton wrote in a March 24 note to clients.
The company had $186 million in cash and short-term investments on Dec. 31, 2021 and said it expects that money to last until it finishes enrolling the Phase 3 study sometime in 2024.