The FDA sent a fresh warn­ing on Thurs­day about Se­cu­ra Bio’s em­bat­tled PI3K in­hibitor Copik­tra (du­velis­ib), which may in­crease the risk of death and se­vere side ef­fects for pa­tients as a third-line treat­ment for adults with chron­ic lym­pho­cyt­ic leukemia (CLL) or small lym­pho­cyt­ic lym­phoma (SLL).

Copik­tra won ap­proval for both in­di­ca­tions in 2018, but the FDA now says that af­ter a me­di­an of 63 months fol­low-up in the Phase III that led to the ap­provals, the fi­nal over­all sur­vival re­sults showed a pos­si­ble in­creased risk of death for those tak­ing Copik­tra, with a haz­ard ra­tio of 1.09 (95% con­fi­dence in­ter­val [CI] 0.79, 1.51). In ad­di­tion, 80/160 of those en­rolled in the tri­al and on Copik­tra end­ed up dy­ing, com­pared with 70/159 of those on No­var­tis’ ofa­tu­mum­ab, FDA said.

“The rate of se­ri­ous side ef­fects, dose mod­i­fi­ca­tions, and deaths re­sult­ing from these side ef­fects were al­so high­er among pa­tients who re­ceived Copik­tra,” FDA added, telling doc­tors to dis­cuss this new da­ta with their pa­tients and de­cide what the best ac­tion is mov­ing for­ward.

This is just the lat­est warn­ing for a class of drugs that has re­ceived in­creased scruti­ny this year, with an FDA ad­comm in April vot­ing that all ap­provals for PI3K in­hibitors should be sup­port­ed by ran­dom­ized da­ta. PI3K in­hibitors gar­nered more scruti­ny re­cent­ly in hema­to­log­i­cal ma­lig­nan­cies af­ter re­newed tox­i­c­i­ty con­cerns, in­ad­e­quate dose op­ti­miza­tion, tri­al de­sign lim­i­ta­tions of sin­gle-arm stud­ies and con­cern­ing over­all sur­vival trends.

Mark Spring

“These safe­ty find­ings were sim­i­lar for oth­er med­i­cines in the same PI3 ki­nase in­hibitor class,” the FDA said in its warn­ing on Copik­tra.

Mean­while, Se­cu­ra Bio in April pulled an ac­cel­er­at­ed ap­proval in­di­ca­tion for Copik­tra as a treat­ment for re­lapsed or re­frac­to­ry fol­lic­u­lar lym­phoma, af­ter the firm failed to run the re­quired con­fir­ma­to­ry tri­al in this in­di­ca­tion.

Se­cu­ra Bio CFO Mark Spring told End­points News pre­vi­ous­ly that Copik­tra’s pulled ac­cel­er­at­ed ap­proval was a mon­ey is­sue, adding:

We felt that com­plet­ing the re­quired Phase 3 tri­al would take too many years and would be too ex­pen­sive. As you can un­der­stand, as a small com­pa­ny we in­vest our fi­nite re­search funds in the ar­eas that we feel will ben­e­fit pa­tients the most and have a rea­son­able re­turn on our in­vest­ment. Se­cu­ra Bio be­lieves that our re­search funds are bet­ter spent on the de­vel­op­ment of COPIK­TRA for the treat­ment of pa­tients with re­lapsed and re­frac­to­ry Pe­riph­er­al T-cell Lym­phoma (r/r PT­CL).

Copik­tra, pur­chased by Se­cu­ra Bio in Sep­tem­ber 2020 from Ve­rastem in a deal val­ued at up to $311 mil­lion-plus roy­al­ties, works by block­ing key sig­nals that cause can­cer cells to mul­ti­ply, which may help re­duce or stop the growth of cer­tain types of can­cer, ac­cord­ing to the FDA.

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.”