After flagging death risks, FDA rescinds accelerated approval for TG Therapeutics' Ukoniq

Approved in February of 2021, TG Therapeutics’ first-in-class drug Ukoniq was billed as a potentially safer treatment for lymphoma patients.

But 16 months later, the FDA has rescinded its approval of Ukoniq because of concerns that its use might increase the risk of death. The risk, along with other adverse side effects, became apparent during a phase 3 trial of the drug in combination with TG's ublituximab in chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) patients.

Ukoniq was originally endorsed to treat marginal zone lymphoma (MZL) and follicular lymphoma (FL). Adding an indication for CLL—which is the most common form of luekemia—would have been a major coup for TG, which doesn’t have another drug on the market.

With the news, TG’s shares dropped 5.5% by the late morning on Wednesday. In response to a request for comment, TG pointed to a release from April 15 when the company announced it was talking Ukoniq off shelves.

In February, the FDA said it taking another look at the med's risks and benefits. At the time, the FDA suspended enrollment in the trial, which was measuring the effectiveness of the Ukoniq combo, which was dubbed "U2," versus a combination of Roche’s Gazyva and chemo drug chlorambucil.

Then in April, TG took Ukoniq off the market and withdrew its biologics license application and supplemental new drug application for approval of the drug in CLL and SLL, saying that overall survival data showed an “increasing imbalance.”

The FDA has told health care professionals to stop prescribing Ukoniq and switch patients to alternative treatments. It also requests them to inform patients currently taking Ukoniq of the increased risk of death seen in the clinical trial and advise them to stop taking the medicine.

In limited circumstances in which a patient may be receiving benefit from Ukoniq, TG Therapeutics plans to make it available under an expanded access program, the FDA said.

Ukoniq is a member of the PI3K-delta inhibitor class. Others in the class that are on the market—including Gilead’s Zydelig and Verastem’s Copiktra—carry black box warnings for side effects. When Ukoniq gained its green light, its label included warnings, but not in a black box.

Upon its approval, Evaluate Pharma predicted sales of Ukoniq would reach $296 million by 2026. An approval for the combo in CLL would have dramatically accelerated its use according to Cantor Fitzgerald analyst Alethia Young, who saw the potential for $1.6 billion in peak sales.