Safe­ty fears spur FDA to pause check­point com­bo stud­ies by Bris­tol-My­ers, Cel­gene

Two months af­ter the FDA or­dered Mer­ck to slam the brakes on three Keytru­da com­bo stud­ies tar­get­ing mul­ti­ple myelo­ma, alarmed reg­u­la­tors have fol­lowed up by post­ing a stop sign on en­rolling any new pa­tients in Bris­tol-My­ers Squibb’s three ri­val stud­ies con­cen­trat­ing on the same dis­ease with the same com­bi­na­tion ap­proach­es. And hours lat­er Cel­gene $CELG added that it is be­ing forced to pause 5 com­bo stud­ies us­ing As­traZeneca’s Imfinzi while get­ting slammed with a full hold on one oth­er.

First to be of­fi­cial­ly frozen in place were Mer­ck’s KEYNOTE-183 and KEYNOTE-185 af­ter re­searchers spot­ted a high­er risk of death in the drug arms. Those mul­ti­ple myelo­ma tri­als matched Mer­ck’s block­buster ther­a­py with two drugs from Cel­gene: Po­m­a­lyst and its big drug Revlim­id. The FDA al­so or­dered pa­tients tak­en off of treat­ment in KEYNOTE-023 Co­hort 1, match­ing Keytru­da in com­bi­na­tion with lenalido­mide and dex­am­etha­sone in pa­tients who re­ceived pri­or an­ti-mul­ti­ple myelo­ma treat­ment with an im­munomod­u­la­to­ry (IMiD) treat­ment (lenalido­mide, po­ma­lido­mide or thalido­mide).

Wor­ried by ev­i­dence of safe­ty is­sues, the FDA fol­lowed up Wednes­day evening by or­der­ing a halt to en­roll­ment of new pa­tients in Bris­tol-My­ers’ stud­ies mar­ry­ing Op­di­vo with the same drugs: CA209602 (Check­Mate-602), CA209039 (Check­Mate-039) and CA204142 — al­so mul­ti­ple myelo­ma com­bo stud­ies.

At Cel­gene the dam­age is worse, with a full hold forc­ing re­searchers drop an ear­ly study look­ing at dur­val­um­ab in com­bi­na­tion with lenalido­mide with and with­out low-dose dex­am­etha­sone in mul­ti­ple myelo­ma pa­tients.

Com­bined, therse com­pa­nies have hun­dreds of com­bo stud­ies un­der­way, but reg­u­la­tors clear­ly be­lieve that there’s some oth­er threat to pa­tients in these par­tic­u­lar com­bi­na­tion stud­ies us­ing Cel­gene’s main­stay ther­a­pies. The FDA high­light­ed that con­cern just a week ago, care­ful­ly spelling out their rea­sons for sus­pend­ing the three Mer­ck stud­ies and point­ing out they were hunt­ing down and re­view­ing oth­er, sim­i­lar PD-(L)1 com­bos in the clin­ic.

Bris­tol-My­ers made for a nat­ur­al first stop in that process, with Cel­gene get­ting tagged at vir­tu­al­ly the same time.

The lat­est or­der from the FDA fol­lowed a stun­ning re­ver­sal for Cel­lec­tis, which was slammed with a clin­i­cal hold on Tues­day af­ter the first pa­tient treat­ed in its de­but off-the-shelf CAR-T study died, un­der­scor­ing the un­known risks that still con­front ad­vanced can­cer pa­tients sign­ing up for these ex­per­i­men­tal im­muno-on­col­o­gy tri­als.

Mer­ck and Bris­tol-My­ers are way out front with check­point in­hibitors Keytru­da and Op­di­vo as their PD-1 su­per­stars con­tin­ue to post jaw-drop­ping re­sults in can­cer. Clear­ly, though, as re­searchers con­tin­ue to test the bound­aries of what these new ther­a­pies can do un­ex­pect­ed safe­ty is­sues con­tin­ue to arise, rais­ing ques­tions of just how far de­vel­op­ers should take the drugs.

That same kind of safe­ty is­sue scut­tled Juno’s lead drug, which wound up killing three pa­tients last year af­ter the FDA pre­ma­ture­ly of­fered a green light to re­sume test­ing of its CAR-T af­ter a brief clin­i­cal hold. At this point, reg­u­la­tors ap­pear to be shift­ing their po­si­tion from an en­cour­ag­ing sig­nal to floor it, to a more cau­tious po­si­tion of study­ing safe­ty threats be­fore bar­rel­ing ahead.

For now, safe­ty is still a gray zone in im­muno-on­col­o­gy, as the da­ta con­tin­ues to pour in.

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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UP­DAT­ED: Stay tuned: Bio­gen’s num­bers are great — it’s their wor­ri­some fu­ture that leaves an­a­lysts skit­tish

Biogen came out with an upbeat assessment of their Q2 numbers today, discounting the arrival of a key rival for its blockbuster Spinraza franchise. But the top execs remain grimly determined to not say much anything new about the sore points that have dragged down its stock, including the future of its big investment in Alzheimer’s or how it plans to invest the considerable cash that the big biotech continues to reap.

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Why wait? Cel­gene re­struc­tures a big Jounce pact — ze­ro­ing in on new I/O path­way with $530M deal and bump­ing ICOS

Celgene’s business team isn’t waiting for the big merger with Bristol-Myers Squibb to go through before syncing its strategy with the new mother ship.

Tuesday evening the big biotech unveiled a $530 million deal — $50 million in upfront cash — to amend their alliance with Jounce Therapeutics $JNCE to gain worldwide rights to JTX-8064, an antibody that targets the LILRB2 receptor on macrophages. Their old, $2.6 billion deal is being scrapped, leaving Jounce with a pipeline that includes the lead drug, the ICOS-targeting vopratelimab.

PACT Phar­ma says it's per­fect­ed the tech to se­lect neoanti­gens for per­son­al­ized ther­a­py — now on­to the clin­ic

At PACT Pharma, the lofty goal to unleash a “tsunami” of T cells personalized for each patient has hinged on the ability to correctly identify the neoantigens that form something of a fingerprint for each tumor, and extract the small group of T cells primed to attack the cancer. It still has a long way to go testing a treatment in humans, but the biotech says it has nailed that highly technical piece of the process.

UP­DAT­ED: My­ovan­t's uter­ine fi­broid drug looks com­pet­i­tive in PhI­II — but can they van­quish mighty Ab­b­Vie?

Vivek Ramaswamy’s Myovant $MYOV has closely matched its positive first round of Phase III data for their uterine fibroid drug relugolix, setting up a head-to-head rivalry with pharma giant AbbVie as the little biotech steers to the market with a planned filing in Q4.

Here’s how Myovant plans to prevail over the AbbVie $ABBV empire.

In the study, 71.2% of women receiving once-daily relugolix combination therapy achieved the clinical response they were looking for, compared to only 14.7% in the control arm. The data comfortably reflected the same outcomes in the first Phase III — 73.4% of women receiving once-daily oral relugolix combination therapy achieved the responder criteria compared with 18.9% of women receiving placebo — which will reassure regulators that they are getting the carefully randomized data that qualifies for the FDA’s gold standard for success.

Lit­tle Mar­i­nus sees its shares eclipsed as the Sage ri­val fails to com­pare on PPD in PhII

The executive team at Sage $SAGE have skirted another potential pitfall on its way to racking up a big future for its depression drug Zulresso.

Little Marinus Pharmaceuticals $MRNS had sought to challenge the Sage drug with an IV formulation — followed by an oral version — of ganaxolone for postpartum depression. But researchers say their Phase II study failed to positively differentiate itself from a placebo at 28 days — leaving them to hold up “clinically meaningful” data within the first day of administration compared to the control arm.

Roche cuts loose Tam­i­flu OTC rights, hand­ing Sanofi the keys as the phar­ma gi­ant dou­bles down on Xofluza

Roche set out to make a better flu medicine than Tamiflu as that franchise was headed to a generic showdown. Now they’ll see just how well Xofluza stacks up against the mainstay drug after handing off over-the-counter rights in the US to Sanofi.

Sanofi $SNY says it will now step in to negotiate a deal with the FDA to steer Tamiflu into the OTC market, a role that could well involve new studies to ease passage of the drug out of doctor’s hands and into the consumer end of the market. And the French pharma giant will have first dibs over “selected” OTC markets around the world as they push ahead.

Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.