Glass half emp­ty: Achao­gen re­ceives split vote from FDA ex­perts on lead an­tibi­ot­ic, shares plunge

An FDA ad­vi­so­ry com­mit­tee has hand­ed down a split vote — yes for one in­di­ca­tion and no for an­oth­er — on Achao­gen’s lead an­tibi­ot­ic, ruf­fling the high ex­pec­ta­tions it set up go­ing in.

In­vestors weren’t hap­py, send­ing Achao­gen stocks down close to 29% in af­ter-hours trad­ing.

The split de­ci­sion car­ries in­ter­est­ing im­pli­ca­tions for oth­er an­tibi­ot­ic mak­ers. In a first, Achao­gen $AKAO sub­mit­ted an NDA with a re­quest to use the Lim­it­ed Pop­u­la­tion An­tibac­te­r­i­al Drug (LPAD) path­way in re­view­ing the drug, pla­zomicin, for the treat­ment of blood­stream in­fec­tions (BSI) due to Car­bapen­em-re­sis­tant En­ter­obac­te­ri­aceae. That hap­pens to be the in­di­ca­tion that the ad­comm vot­ed down; all 15 of them vot­ed yes when it came to treat­ing pa­tients with com­pli­cat­ed uri­nary tract in­fec­tions (cU­TI).

Pack­aged in­to the 2016 21th Cen­tu­ry Cures Act, the LPAD reg­u­la­to­ry path­way al­lows for ac­cep­tance of greater un­cer­tain­ty or high­er risk in pa­tients with se­ri­ous dis­eases (and an un­met need) pro­vid­ed that sub­stance ev­i­dence of ef­fec­tive­ness is pre­sent­ed.

A large part of what seems to have doomed Achao­gen’s plans for the BSI in­di­ca­tion was a small­er-than-ex­pect­ed sam­ple size that com­pli­cat­ed sta­tis­ti­cal analy­sis. Ear­ly in the meet­ing, an FDA clin­i­cal re­view­er point­ed out that the biotech had to amend pro­to­cols for a Phase III study (ACHN-490-007) be­cause they could on­ly en­roll 37 pa­tients out of the 286 planned. That re­sult­ed in sta­tis­ti­cal lim­i­ta­tions in con­clud­ing that pla­zomicin had su­pe­ri­or ef­fi­ca­cy com­pared to col­istin in the com­para­tor arm, even though nu­mer­i­cal trends point­ed to that con­clu­sion.

The re­view­er went on to sug­gest look­ing at the da­ta through the lens of non­in­fe­ri­or­i­ty, which the da­ta would al­low for, but cau­tioned that such as­sess­ments are com­pli­cat­ed by de­sign fea­tures the FDA agreed to back when Achao­gen was plan­ning a su­pe­ri­or­i­ty tri­al. Among those fea­tures: pri­or or con­comi­tant an­tibac­te­r­i­al ther­a­py, as well as lax­er cri­te­ria for pa­tients re­gard­ing bac­te­ria cul­ture in their bod­ies. That ad­di­tion­al un­cer­tain­ty re­gard­ing base­line sta­tus for pa­tients didn’t help, ei­ther.

Af­ter dis­cussing the sta­tis­ti­cal plan and clar­i­fy­ing how best to bal­ance the LPAD con­sid­er­a­tion with ben­e­fit-risk as­sess­ments, 11 com­mit­tee mem­bers vot­ed against pla­zomicin in BSI, most­ly con­cerned that the study was un­der­pow­ered to sup­port con­clu­sions of ef­fi­ca­cy. The oth­er four dis­agreed, cit­ing the lim­it­ed use and un­met need.

For cU­TI, on the oth­er hand, com­mit­tee mem­bers had no prob­lem unan­i­mous­ly en­dors­ing pla­zomicin based on a study that showed its was non­in­fe­ri­or to meropen­em, even con­sid­er­ing a larg­er mar­gin of 15% (ver­sus a con­ven­tion­al 10%) the FDA sanc­tioned.

Achao­gen CEO Blake Wise had this to say in a short state­ment:

We are en­cour­aged by the Com­mit­tee’s unan­i­mous vote in fa­vor of pla­zomicin for com­pli­cat­ed uri­nary tract in­fec­tions (cU­TI). The dis­cus­sion un­der­scored the re­al-world chal­lenges that health­care providers face every day giv­en lim­it­ed or in­ad­e­quate treat­ment op­tions for cer­tain pathogens. Re­gard­ing blood­stream in­fec­tions, the Lim­it­ed-Pop­u­la­tion An­tibac­te­r­i­al Drug path­way, or LPAD, is a nov­el ap­proach that en­ables the FDA to con­sid­er the ben­e­fits and risks for the sick­est pa­tients who have few or no avail­able treat­ment op­tions, and to ap­prove an­tibi­otics like pla­zomicin that we be­lieve, have the po­ten­tial to ad­dress these lim­it­ed pa­tient pop­u­la­tions.

South San Fran­cis­co-based Achao­gen is one of a hand­ful of biotechs in late-stage de­vel­op­ment with new an­tibi­otics in an era of ris­ing drug re­sis­tance to the main­stays in the field. Whether it will be­come a trail­blaz­er or a cau­tion­ary tale will be­come clear by its PDU­FA date of June 25.

UP­DAT­ED: Mer­ck pulls Keytru­da in SCLC af­ter ac­cel­er­at­ed nod. Is the FDA get­ting tough on drug­mak­ers that don't hit their marks?

In what could be an early shot in the battle against drugmakers that whiff on confirmatory studies to support accelerated approvals, the FDA ordered Bristol Myers Squibb late last year to give up Opdivo’s approval in SCLC. Now, Merck is next on the firing line — are we seeing the FDA buckling down on post-marketing offenders?

Merck has withdrawn its marketing approval for PD-(L)1 inhibitor Keytruda in metastatic small cell lung cancer as part of what it describes as an “industry-wide evaluation” by the FDA of drugs that do not meet the post-marketing checkpoints on which their accelerated nods were based, the company said Monday.

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Pascal Soriot, AstraZeneca CEO (AP Images)

Pas­cal So­ri­ot cash­es in As­traZeneca’s chips on Mod­er­na for $1.2B cash in­jec­tion

While still working to prove its own Covid-19 vaccine, AstraZeneca has reportedly capitalized on the success of another.

The company has sold off its 7.7% stake in Moderna and turned it into $1.2 billion in cash, according to the Times, beefing up the reserves just as Pascal Soriot is wrapping up his $39 billion acquisition of Alexion and its rare disease pipeline.

AstraZeneca’s stock sale follows a similar move by Merck in December. But like its pharma brethren, the British giant is keeping its R&D collaborations with Moderna.

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Bob Nelsen (Photo by Michael Kovac/Getty Images)

With stars aligned and cash in re­serve, Bob Nelsen's Re­silience plans a makeover at 2 new fa­cil­i­ty ad­di­tions to its drug man­u­fac­tur­ing up­start

Bob Nelsen’s new, state-of-the-art drug manufacturing initiative is taking shape.

Just 3 months after gathering $800 million of launch money, a dream team board and a plan to shake up a field where he found too many bottlenecks and inefficiencies for the era of Covid-19, Resilience has snapped up a pair of facilities now in line for a retooling.

The company has acquired a 310,000-square-foot plant in Boston from Sanofi along with a 136,000-square-foot plant in Ontario to add to a network which CEO Rahul Singhvi says is just getting started on building his company’s operations up. The Sanofi deal comes with a contract to continue manufacturing one of its drugs.

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Af­ter bail­ing on Covid-19 vac­cines, Mer­ck will team up with J&J to pro­duce its shot as part of un­usu­al Big Phar­ma pact

Merck took a big gamble when it opted to jump into the Covid-19 vaccine race late, and made an equally momentous decision to back out in late January. Now, looking to chip in on the effort, Merck reportedly agreed to team up with one of the companies that has already crossed the finish line.

President Joe Biden on Tuesday is expected to announce a partnership between drugmakers Merck and Johnson & Johnson to jointly produce J&J’s recombinant protein Covid-19 vaccine that received the FDA’s emergency use authorization Saturday, the Washington Post reported.

Ab­b­Vie tees up a biotech buy­out af­ter siz­ing up their Parkin­son's drug spun out of Ke­van Shokat's lab

AbbVie has teed up a small but intriguing biotech buyout after looking over the preclinical work it’s been doing in Parkinson’s disease.

The company is called Mitokinin, a Bay Area biotech spun out of the lab of UCSF’s Kevan Shokat, whose scientific explorations have formed the academic basis of a slew of startups in the biotech hub. One of Shokat’s PhD students in the lab, Nicholas Hertz, co-founded Mitokinin using their lab work on PINK1 suggesting that amping up its activity could play an important role in regulating the mitochondrial dysfunction contributing to Parkinson’s disease pathogenesis and progression.

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Paul Sekhri

The next big biotech su­per­star? Paul Sekhri has some thoughts on that

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“I just want to be laser-focused on getting to that point,” Sekhri says, before acknowledging, “Yes, it absolutely crossed my mind.”

Sekhri, a longtime biopharma executive with tenures at Sanofi and Novartis, is now entering year three as CEO of eGenesis, the biotech that George Church protégé Luhan Yang founded to genetically alter pigs so that they can be used for organ transplants. He led them through one megaround and has just closed another, raising $125 million from 17 different investors to push the first-ever (humanized) pig to human transplants into the clinic.

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Fi­bro­Gen shares skid low­er as a sur­prise ad­comm rais­es risks on roxa OK

FibroGen will likely have to delay its US rollout for roxadustat once again.

In an unexpected move, the FDA is convening its Cardiovascular and Renal Drugs Advisory Committee to review the NDA in an advisory committee meeting. The date is yet to be confirmed.

Just a few weeks ago, SVB Leerink analyst Geoffrey Porges predicted that the roxa approval could come ahead of the PDUFA date on March 20 — effusive despite already being let down once by the FDA’s extension of its review back in December. AstraZeneca, which is partnered with FibroGen on the chronic kidney disease-related anemia drug, disclosed regulators had requested further clarifying analyses of clinical data.

In­tro­duc­ing End­pointsF­DA+, our new pre­mi­um week­ly reg­u­la­to­ry news re­port led by Zachary Bren­nan

CRLs. 483s. CBER, CDER and RWE. For biopharma professionals, these acronyms command attention because of the fundamental role FDA plays in drug development. Now Endpoints is doubling down on regulatory coverage, and launching a weekly report focusing on developments out of White Oak, with analysis and insight into what it all means.

Coverage will be led by our new senior editor, Zachary Brennan. He joins Endpoints from POLITICO, where he covered pharma. Prior to that he was the managing editor for Regulatory Focus, a news publication from the Regulatory Affairs Professionals Society.

Amit Munshi, Arena

One of Are­na's top drugs flops in a PhI­Ib study for IBS pain. But re­searchers tease out a pos­si­ble path for­ward as CEO ex­plores 's­trate­gic op­tion­s'

Four years ago, when Arena CEO Amit Munshi cut its ties to a troubled weight drug and doubled down on the pipeline, a cannabinoid receptor 2 agonist figured prominently in the biotech’s future. On Tuesday evening, however, Munshi’s high hopes for the drug took a nasty hit after it failed a Phase IIb study for patients with irritable bowel syndrome pain.

Put through a randomized pace with 273 patients, researchers said it flat failed the primary endpoint among the large group with abdominal pain. But they quickly went on to highlight subgroup data, always a tricky and controversial ploy, where they spotlighted a positive p value for patients with moderate to severe pain who received the high dose of the drug — one of 3 provided in the study.