In-house FDA re­view flags a sus­pi­cious im­bal­ance in deaths as Sh­iono­gi hunts an OK for an­tibi­ot­ic

Sh­iono­gi has some big ques­tions to an­swer if they plan to win an FDA pan­el’s back­ing for their new an­tibi­ot­ic.

While in­ves­ti­ga­tors have pro­vid­ed pos­i­tive ef­fi­ca­cy da­ta for their new prod­uct to treat cas­es of com­plex uri­nary tract in­fec­tions, an FDA re­view has flagged an im­bal­ance of deaths be­tween the an­tibi­ot­ic and a con­trol arm — with a “high­er mor­tal­i­ty in ce­fide­ro­col-treat­ed pa­tients was ob­served in a tri­al in crit­i­cal­ly ill pa­tients with a va­ri­ety of in­fec­tions due to car­bapen­em-re­sis­tant or­gan­isms.”

And they want the agency’s out­side ad­vis­ers to take a good hard look at that when they meet on Wednes­day.

The an­tibi­ot­ic arm in ques­tion had a sig­nif­i­cant gap  when re­searchers count­ed deaths, ac­cord­ing to an in­ter­nal re­view at the FDA.

The CRED­I­BLE-CR study was a de­scrip­tive study with no pre-spec­i­fied hy­poth­e­sis test­ing. The study com­plet­ed en­roll­ment dur­ing the NDA re­view; datasets were sub­mit­ted to the Agency for re­view and the clin­i­cal study re­port was not sub­mit­ted. In this tri­al, pa­tients with HABP/VABP, cU­TI, and BSI/sep­sis due to car­bapen­em-re­sis­tant or­gan­isms were ran­dom­ized to re­ceive ce­fide­ro­col or BAT, of which 66% were col­istin-based reg­i­mens. All-cause mor­tal­i­ty was high­er in the ce­fide­ro­col group com­pared to the BAT group at Day 14 (18.8% ver­sus 12.2%) and Day 28 (24.8% ver­sus 18.4%) re­spec­tive­ly. The great­est mor­tal­i­ty dif­fer­ence dis­fa­vor­ing ce­fide­ro­col was not­ed in the HABP /VABP /HCABP sub­group, fol­lowed by the BSI/sep­sis sub­group. An in­de­pen­dent ad­ju­di­ca­tion com­mit­tee de­ter­mined that a greater per­cent­age of pa­tients in the ce­fide­ro­col group than in the BAT group had in­fec­tion-re­lat­ed death with treat­ment fail­ure (15.8% vs. 8.2%), but al­so not­ed an im­bal­ance in death due to un­der­ly­ing co-mor­bidi­ties (9.9% vs. 4.1%).

Now an ad­vi­so­ry com­mit­tee will take that up on Wednes­day be­fore vot­ing on whether or not the FDA should green light the new an­tibi­ot­ic at a time of ris­ing drug re­sis­tance. Says the FDA:

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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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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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

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Cameron Durrant, Humanigen CEO (Columbia University Technology Ventures via YouTube)

Cameron Dur­rant hus­tled his way from the OTC side­lines right in­to the Covid-19 drug race. Death or glo­ry lies straight ahead

Over the past few months, Covid-19 has gone from being a monolithic threat to one of the biggest overnight boons the biopharma industry has ever seen. And amid all the furor over Moderna’s swelling stock price, plenty of chatter over what new drugs and vaccines will cost and investors’ uninhibited zeal for all things related to pandemic products, it’s been one little biotech’s golden ticket back from the land of the living dead.

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Credit: AP Images

Covid-19 roundup: BAR­DA sup­ports Op­er­a­tion Warp Speed with big $628M con­tract to ser­vice Amer­i­ca's vac­cine pro­duc­tion needs

Another BARDA contract designed to service America’s Covid-19 vaccine needs has been deployed.

The White House-led initiative designed to bankroll development to bring a vaccine to the American public by this fall — Operation Warp Speed — has via BARDA handed a meaty contract to the maker of an FDA-licensed anthrax vaccine to open up its manufacturing apparatus to shore up production of Covid-19 vaccines.

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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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Adam Keeney (NodThera)

As NL­RP3 play­ers head for first clin­i­cal face-off, No­vo, Sanofi fu­el trans-At­lantic con­tender with $55M

In the relative short history of inflammasome research, Adam Keeney sees two time points marking major breakthroughs: the early 2000s, when the role of inflammasomes as a major innate immunity node was elucidated; and 2015, when Pfizer found out a compound it thought was targeting IL-1 actually blocks NLRP3. Keeney’s biotech, NodThera, was founded the year after alongside several others to create its own superior small molecule drugs.

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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