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: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

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UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

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IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

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That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.