FDA cites in­creased death risk in de­ci­sion to yank ap­proval for TG Ther­a­peu­tics can­cer drug

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.

Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Idor­si­a's brain bleed drug flunks PhI­II tri­al, a decade af­ter pre­vi­ous flop

Idorsia’s long journey with clazosentan came to an abrupt “unexpected result” Monday morning with a Phase III flop.

The Swiss biopharma said the drug did not meet the main goal of the late-stage REACT study, conducted in the US, Canada and Europe since early 2019.

The 409-patient trial tested the intravenous drug’s ability to prevent complications due to delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage (aSAH), in which blood vessels in the brain narrow and blood accumulates around the brain’s surface, which then dials up the pressure on the brain.

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Kenji Yasukawa, Astellas Pharma CEO (Photographer: Akio Kon/Bloomberg via Getty Images)

Astel­las taps chief strat­e­gy of­fi­cer as next CEO to 'go on the ag­gres­sive'

Five years into its big R&D revamp, Astellas says it’s time for a changing of the guard.

Kenji Yasukawa, who took over as president and CEO in 2018, will step down to become chairman of the board in April, making room for Naoki Okamura to take over. Okamura joined the company in 1986 and has served in a variety of finance, business and strategy roles, including most recently as chief strategy officer.

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Clin­i­cal tri­al di­ver­si­ty da­ta show mis­match be­tween en­roll­ment and dis­ease preva­lence, GSK says

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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

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 ap­proves GSK's ane­mia drug with safe­ty warn­ing — af­ter bat­ting back sim­i­lar drugs

GSK has secured the first of four US approvals it’s hoping for this year, as the FDA greenlit daprodustat as a treatment for anemia due to chronic kidney disease.

But the FDA limited the use of the drug, to be marketed as Jesduvroq, to patients who have been receiving dialysis for at least four months and stopped short of approving it for patients not dependent on dialysis — in line with the recommendations of the advisory committee it consulted.

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Photo: Julia Weeks/AP Images

FDA ax­es re­quire­ment for pos­i­tive Covid test be­fore Paxlovid use

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.”

Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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David Kirn, 4D Molecular Therapeutics CEO (via website)

FDA places hold on 4D Mol­e­c­u­lar’s Fab­ry gene ther­a­py

4D Molecular Therapeutics quietly tucked an FDA clinical hold on its Fabry gene therapy into an SEC filing.

Meanwhile, the biotech issued a press release the same day after the closing bell on Thursday touting an IND for another asset, in diabetic macular edema.

The California biotech had paused enrollment of patients in its two trials of the Fabry gene therapy (4D-310) last month after three patients experienced kidney issues, all of which were resolved within four weeks. At the time, 4DMT said it would wait until the second half of this year to look at 12-month clinical data on six patients in the Phase I/II trials, one in the US and one in Taiwan and Australia.

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