FDA raises concerns over TG Therapeutics’ survival data, plans to convene ODAC

Michael Weiss, TG Therapeutics CEO

TG Ther­a­peu­tics took a hit Tues­day morn­ing af­ter an­nounc­ing the FDA will con­vene an ad­comm ahead of the biotech’s up­com­ing PDU­FA date for a blood can­cer com­bo ther­a­py, throw­ing a po­ten­tial de­ci­sion in­to lim­bo.

Though the ex­act date has not been de­ter­mined, reg­u­la­tors are look­ing to hold a meet­ing of the On­co­log­ic Drugs Ad­vi­so­ry Com­mit­tee some­time in March or April, TG said in a re­lease. Giv­en that tim­ing, the biotech says it’s now un­like­ly the FDA will reach an ap­proval de­ci­sion by the March 25 dead­line.

‘We look for­ward to the ODAC meet­ing as we be­lieve it will pro­vide us an op­por­tu­ni­ty to high­light the im­por­tant role U2 can play in the treat­ment of CLL,’ CEO Michael Weiss said in a state­ment.

In the wake of the news, TG shares $TGTX cratered by near­ly 45% as the mar­ket opened Tues­day morn­ing.

The pro­gram in ques­tion is a com­bi­na­tion of ubli­tux­imab and um­bral­is­ib, which the biotech has re­ferred to as U2 (no re­la­tion to the Bono-led band). TG has been re­search­ing the ther­a­py to treat adults with chron­ic lym­pho­cyt­ic leukemia and small lym­pho­cyt­ic lym­phoma.

Ac­cord­ing to TG, the FDA is call­ing ODAC to­geth­er over ques­tions about the pro­gram’s over­all sur­vival ben­e­fits, some­thing that was not an­a­lyzed in the in­ter­im analy­sis, Weiss said in an in­vestor call Tues­day. OS had been in­clud­ed as a sec­ondary mea­sure, but was in­stead pow­ered to mea­sure pro­gres­sion-free sur­vival.

TG pro­vid­ed sur­vival in­fo to reg­u­la­tors as part of the BLA and sN­DA re­view, but Weiss not­ed it was not in­clud­ed orig­i­nal­ly. The CEO said TG and the FDA had agreed be­fore the study that the sur­vival da­ta would have been too im­ma­ture and ‘too small to be in­for­ma­tive’ had the com­pa­ny at­tempt­ed to mea­sure OS.

The da­ta TG even­tu­al­ly pro­vid­ed in­clud­ed an ear­ly analy­sis show­ing no sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence in sur­vival be­tween the treat­ment arms, Weiss said. He high­light­ed that the haz­ard ra­tio of 1.23 ap­peared to show an im­bal­ance in fa­vor of the con­trol arm, though when ex­clud­ing deaths re­lat­ed to Covid-19, the HR fell to 1.04 — again with no sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence.

Weiss al­so at­tempt­ed to ease in­vestor con­cerns over the hear­ing, ex­plain­ing that there is ‘prece­dent’ for the ap­proval of drugs that seem­ing­ly fa­vor sur­vival con­trol arms. He point­ed to Ab­b­Vie and Roche’s Ven­clex­ta as one ex­am­ple, not­ing the drug had ‘no ODAC and OS was clear­ly in fa­vor of the GC arm at the time of ap­proval,’ in re­sponse to an an­a­lyst ques­tion.

Time will tell whether ODAC heeds the FDA’s con­cerns, but the news marks an­oth­er bump in TG’s quest to get the U2 com­bo past the fin­ish line — tim­ing that re­mains up in the air. In Sep­tem­ber 2018, the biotech was sup­posed to read out ORR da­ta for the ther­a­py but the safe­ty mon­i­tor­ing board said at the time the da­ta weren’t ma­ture enough.

TG brought in­vestors back to the ta­ble in May 2020, how­ev­er, read­ing out pos­i­tive topline Phase III re­sults that showed it hit the PFS thresh­old in an in­ter­im analy­sis. In the full dataset re­vealed at ASH in De­cem­ber 2020, TG showed off stel­lar p-val­ues in PFS and ORR (p<0.0001 and p<0.001, re­spec­tive­ly) while say­ing um­bral­is­ib as a monother­a­py al­so hit a 49.3% over­all re­sponse rate.

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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The FDA’s Oncologic Drugs Advisory Committee has decided to cancel a planned meeting on Thursday to discuss two cancer drugs that previously won accelerated approvals but failed to confirm clinical benefit in required follow-up trials or have taken a long time to finish those trials.

The FDA said in a statement that the meeting ‘is no longer needed’ but did not offer further detail on why exactly it was canceled, telling Endpoints News to contact the companies. Attempts to contact both Secura Bio and Acrotech went unreturned. The companies may have decided to pull these treatments from the market, or they’ve come to new agreements with the agency on their confirmatory trials.

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a ‘select number of key European markets.’

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Mark Enyedy, ImmunoGen CEO

When ImmunoGen’s lead antibody-drug conjugate flunked a Phase III study in ovarian cancer a couple years ago, the company clung to hope that it would perform better in a subgroup of patients with high folate receptor alpha (FRα) expression.

On Tuesday, researchers uncorked topline Phase III results suggesting it was right — and investors cheered on the news with a 40% boost to ImmunoGen’s stock price $IMGN. CEO Mark Enyedy says he’s going after an accelerated approval and plans to file in the first quarter of 2022.

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.
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