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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Ken Frazier, AP Images

Why Mer­ck wait­ed, and what they now bring to the Covid-19 fight

Nicholas Kartsonis had been running clinical infectious disease research at Merck for almost 2 years when, in mid-January, he got a new assignment: Searching the Pharma giant’s vast libraries for something that could treat the novel coronavirus.

The outbreak was barely two weeks old when Kartsonis and a few dozen others got to work, first in small teams and then in a larger task force that sucked in more and more parts of the sprawling company as Covid-19 infected more and more of the globe. By late February, the group began formally searching for vaccine and antiviral candidates to license. Still, while other companies jumped out to announce their programs and, eventually and sometimes controversially, early glimpses at human data, Merck remained silent. They made only a brief announcement about a data collection partnership in April and mentioned vaguely a vaccine and antiviral search in their April 28 earnings call.

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Mark Genovese (Stanford via Twitter)

Gilead woos fil­go­tinib clin­i­cal in­ves­ti­ga­tor from Stan­ford to lead the charge on NASH, in­flam­ma­to­ry dis­eases

With an FDA OK for the use of filgotinib in rheumatoid arthritis expected to drop any day now, Gilead has recruited a new leader from academia to lead its foray into inflammatory diseases.

Mark Genovese — a longtime Stanford professor and most recently the clinical chief in the division of immunology and rheumatology — was the principal investigator in FINCH 2, one of three studies that supported Gilead’s NDA filing. In his new role as SVP, inflammation, he will oversee the clinical development of the entire portfolio.

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Gilead re­leas­es an­oth­er round of murky remde­sivir re­sults

A month after the NIH declared the first trial on remdesivir in Covid-19 a success, Gilead is out with new results on their antiviral. But although the study met one of its primary endpoints, the data are likely to only add to a growing debate over how effective the drug actually is.

In a Phase III trial, patients given a 5-day dose of remdesivir were 65% more likely to show “clinical improvement” compared to an arm given standard-of-care. The trial, though, gave little indication for whether the drug had an impact on key endpoints such as survival or time-to-recovery. And in a surprising twist, a 10-day dosing arm of remdesivir didn’t lead to a statistically significant improvement over standard of care.

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Stephen Isaacs, Aduro president and CEO (Aduro)

Once a high fly­er, a stag­ger­ing Aduro is auc­tion­ing off most of the pipeline as CEO Stephen Isaacs hands off the shell to new own­ers

After a drumbeat of failure, setbacks and reorganizations over the last few years, Aduro CEO Stephen Isaacs is handing over his largely gutted-out shell of a public company to another biotech company and putting up some questionable assets in a going-out-of-business sale.

Isaacs —who forged a string of high-profile Big Pharma deals along the way — has wrapped a 13-year run at the biotech with one program for kidney disease going to the new owners at Chinook Therapeutics. A host of once-heralded assets like their STING agonist program partnered with Novartis (which dumped their work on ADU-S100 after looking over weak clinical results), the Lilly-allied cGAS-STING inhibitor program and the anti-CD27 program out-licensed to Merck will all be posted for auction under a strategic review process.

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Hill­house re­casts spot­light on Chi­na's biotech scene with $160M round for Shang­hai-based an­ti­body mak­er

Almost two years after first buying into Genor Biopharma’s pipeline of cancer and autoimmune therapies, Hillhouse Capital has led a $160 million cash injection to push the late-stage assets over the finish line while continuing to fund both internal R&D and dealmaking.

The Series B has landed right around the time Genor would have listed on the Hong Kong stock exchange, according to plans reported by Bloomberg late last year. Insiders had said that the company was looking to raise about $200 million.

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No­var­tis chips in $10M for IPO-bound part­ner Pli­ant; Tenax shares soar on heart drug da­ta

Novartis is coming in with $10 million to help support the looming IPO of a partner. Pliant Therapeutics posted a new filing with the SEC showing that Novartis is buying the shares at $15, the mid-point of the range. It’s adding several million shares to the offering, bringing the total to around $135 million. Biotech companies have been enjoying quite a run on virtual Wall Street, with investors boosting new offerings to some big hauls.

Federico Mingozzi (Spark)

Spark touts an­i­mal da­ta for a so­lu­tion to AAV gene ther­a­py's an­ti­body prob­lem

Among all the limitations of using an adeno-associated virus as a vector to deliver a gene — still the most established modality in gene therapy given years of trial and error and finally success — the presence of neutralizing antibodies, whether pre-existing or induced, looms large.

“When I think about the immune responses in AAV, I try to sort of layer them,” Federico Mingozzi, the CSO at Spark Therapeutics, told Endpoints News. “The antibody is the first layer. It’s the first block that you find when you’re trying to do gene transfer.”