Fol­low­ing pre­vi­ous­ly re­vealed safe­ty con­cerns, the FDA on Wednes­day said it has with­drawn TG Ther­a­peu­tics’ can­cer drug Ukoniq to treat two spe­cif­ic types of lym­phoma, mar­gin­al zone lym­phoma and fol­lic­u­lar lym­phoma.

The de­ci­sion comes as up­dat­ed find­ings from an on­go­ing tri­al of the drug, known gener­i­cal­ly as um­bral­is­ib, show an in­creased risk of death in pa­tients, and FDA said the risks of treat­ment with Ukoniq out­weigh its ben­e­fits.

“Health care pro­fes­sion­als should stop pre­scrib­ing Ukoniq and switch pa­tients to al­ter­na­tive treat­ments. In­form pa­tients cur­rent­ly tak­ing Ukoniq of the in­creased risk of death seen in the clin­i­cal tri­al and ad­vise them to stop tak­ing the med­i­cine,” FDA said in a state­ment.

TG Ther­a­peu­tics in April vol­un­tar­i­ly with­drew um­bral­is­ib, as well as its BLA and sN­DA for the blood can­cer com­bo pro­gram U2, of which um­bral­is­ib is a com­po­nent, cit­ing sur­vival da­ta that fa­vored the con­trol arm over the drug.

The biotech al­so an­nounced yes­ter­day that the FDA al­so ex­tend­ed the PDU­FA date to Dec. 28 for ubli­tux­imab, the oth­er half of U2, as a po­ten­tial drug for re­laps­ing forms of mul­ti­ple scle­ro­sis.

But these safe­ty ques­tions for Ukoniq have been per­co­lat­ing since late last year, as sur­vival da­ta had been a point of con­tention since No­vem­ber 2021, when TG first an­nounced the FDA’s plans to hold a 2-day ad­comm that was sup­posed to dis­cuss U2, but was lat­er can­celed. The FDA is­sued its first warn­ing of po­ten­tial in­creased risk of death with Ukoniq in Feb­ru­ary.

Michael Weiss

In April, TG al­lud­ed to a “re­cent in­for­ma­tion re­quest” from the FDA that showed sur­vival re­sults dif­fered from an analy­sis sub­mit­ted in Feb­ru­ary. That sub­mis­sion con­tained non-spe­cif­ic “im­prove­ments” over an ear­ly analy­sis show­ing a 1.04 haz­ard ra­tio, sug­gest­ing more pa­tients died tak­ing the drug than those in the con­trol arm.

De­spite the im­prove­ments, “nei­ther the orig­i­nal pre­lim­i­nary OS re­sults nor the up­dat­ed pre­lim­i­nary OS re­sults were sta­tis­ti­cal­ly sig­nif­i­cant,” TG Ther­a­peu­tics added.

At the time, CEO Michael Weiss not­ed the sur­vival analy­sis was not in­clud­ed in the orig­i­nal NDA, and that the Phase III was not pow­ered to mea­sure sur­vival.

A lack of diversity in clinical trials has persisted despite decades of initiatives to try to turn the tide.

In a recent review of 17 years of clinical trials, drugmaker GSK found that there were some mismatches between the demographics of its US-based trials and how prevalent diseases were in those populations.

The results, the company says, will help GSK and others design studies that better represent epidemiological rates within races and ethnicities.

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

FDA announced today that doctors and pharmacists can now prescribe Paxlovid to patients without a positive test for Covid-19.

CDER Director Patrizia Cavazzoni reissued Paxlovid’s authorization letter Wednesday, saying it has revised the authorization to “no longer require positive results of direct SARS-CoV-2 viral testing.” The EUA now requires instead that adults and kids 12 years of age and older have a “current diagnosis of mild-to-moderate COVID-19.”