Nabri­va goes 2 for 2 in Phase III an­tibi­ot­ic pro­gram, scor­ing on a key cat­a­lyst -- but shares plunge on safe­ty wor­ries

Nabri­va Ther­a­peu­tics $NBRV has scored a sec­ond, piv­otal Phase III win for its an­tibi­ot­ic lefa­mulin in com­mu­ni­ty ac­quired bac­te­r­i­al pneu­mo­nia — set­ting up a pitch to the FDA lat­er this year and quite like­ly clear­ing a path to its first com­mer­cial launch.

Their an­tibi­ot­ic achieved non-in­fe­ri­or­i­ty com­pared to mox­i­floxacin for ear­ly clin­i­cal re­sponse (ECR) — 72 to 120 hours fol­low­ing ini­ti­a­tion of ther­a­py in the in­tent to treat pa­tient pop­u­la­tion. In this tri­al, ECR rates were 90.8% for lefa­mulin and 90.8% for mox­i­floxacin. The tri­al al­so achieved Eu­ro­pean goals out­lined for an ap­proval.

Nabri­va’s shares rock­et­ed up 24% on the news, and then re­versed course as in­vestors wres­tled over the safe­ty da­ta, falling 17% by the end of trad­ing. Di­ar­rhea proved a more ex­pan­sive con­cern than the ef­fi­ca­cy da­ta, with the an­tibi­ot­ic arm do­ing worse than moxi. Tox­i­c­i­ty is­sues grabbed in­vestors by the throat, with plen­ty of fret­ting about po­ten­tial lim­its to its use.

A cru­cial cat­a­lyst for this biotech, lefa­mulin came out of the sec­ond late-stage study look­ing iden­ti­cal to moxi, fit­ting a pro­file reg­u­la­tors re­quire for a mar­ket­ing ap­proval. If every­thing goes ac­cord­ing to plan, and gets around the safe­ty wor­ries, that will set up a launch in 2019 as the biotech seeks to carve out a large seg­ment of a big mar­ket, and not just due to drug re­sis­tance.

Col­in Broom

“I do not see this as an an­tibi­ot­ic to keep in re­serve,” CEO Col­in Broom tells me in a pre­view of the news. “It’s a short course of ther­a­py (5 days for lefa­mulin com­pared to 7 days for moxi), high­ly ef­fec­tive, with com­plete cov­er­age of the pathogens we wor­ry about….It’s re­al­ly the on­ly an­tibi­ot­ic out there that has the op­por­tu­ni­ty to be used out of the gate.”

Mak­ing that ar­gu­ment stick with pay­ers will re­quire some mod­er­a­tion on the pric­ing, he adds, with­out spelling out the num­bers. An­a­lysts will like­ly stay mind­ful that pay­ers will keep fo­cused on price, al­ways re­quir­ing cheap gener­ics when­ev­er pos­si­ble.

The biotech al­so re­port­ed that one pa­tient in their study al­so de­vel­oped C diff dur­ing an ex­tend­ed hos­pi­tal stay.

Gary Sender

Nei­ther Broom nor CFO Gary Sender are of­fer­ing their own peak sales es­ti­mates, but the CFO notes that an­a­lysts cov­er­ing the com­pa­ny have pen­cilled in es­ti­mates rang­ing from $500 mil­lion to $700 mil­lion a year — and they ex­pect those an­a­lysts to do some re­cal­cu­la­tions in their fa­vor with the lat­est batch of piv­otal da­ta.

Even now Nabri­va has a sales force of 20 work­ing the pre-com­mer­cial­iza­tion mar­ket. That will like­ly ex­pand to the 30-to-60 range, says the CEO, and even­tu­al­ly up to around 100. Broom ex­pects to line up part­ners for the ex-US mar­ket.

In do­ing so, Nabri­va may soon find it­self go­ing up against Paratek’s an­tibi­ot­ic, which al­so suc­ceed­ed for CABP and was filed for an ap­proval in Feb­ru­ary. Broom shrugs that off, though, dis­count­ing the ri­val as a broad spec­trum al­ter­na­tive that will like­ly be held in re­serve, al­low­ing lefa­mulin to push ahead in­to a broad­er mar­ket.

It won’t hurt Nabri­va that the FDA height­ened its warn­ings against the use of flu­o­ro­quinolones like maxi a cou­ple of years ago, af­ter iden­ti­fy­ing new safe­ty is­sues that in­cludes dis­abling side ef­fects in­volv­ing ten­dons, mus­cles, joints and nerves. And he adds that the com­mon­ly used z packs have be­come lit­tle bet­ter than a place­bo for about half of all cas­es of bac­te­r­i­al pneu­mo­nia.

Still, for years now the de­vel­op­ment of new an­tibi­otics has been left to small biotechs like Nabri­va, af­ter Big Phar­ma’s large­ly bowed out of a field they iden­ti­fied with nar­row mar­gins — de­spite the grow­ing num­ber of alarms from mul­ti­tude of glob­al health agen­cies over a steadi­ly ris­ing tide of drug re­sis­tance. It’s not an easy field, as a slate of re­cent clin­i­cal mishaps un­der­score. And cheap gener­ics are typ­i­cal­ly thrown at cas­es as they arise.

Broom, though, like oth­er CEOs in the field, be­lieves the eco­nom­ics of an­tibi­otics will grad­u­al­ly im­prove as more cas­es of re­sis­tance rise up. And he plans to be there with one of the new breed when it does.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

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It's not per­fect, but it's a good start: FDA pan­elists large­ly en­dorse Aim­mune's peanut al­ler­gy ther­a­py

Two days after a fairly benign review from FDA staff, an independent panel of experts largely endorsed the efficacy and safety of Aimmune’s peanut allergy therapy, laying the groundwork for approval with a risk evaluation and mitigation strategy (REMS).

Traditionally, peanut allergies are managed by avoidance, but the threat of accidental exposure cannot be nullified. Some allergists have devised a way to dose patients off-label with peanut protein derived from supermarket products to wean them off their allergies. But the idea behind Aimmune’s product was to standardize the peanut protein, and track the process of desensitization — so when accidental exposure in the real world invariably occurs, patients are less likely to experience a life-threatening allergic reaction.

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Lisa M. DeAngelis, MSKCC

MSK picks brain can­cer ex­pert Lisa DeAn­ge­lis as its next CMO — fol­low­ing José Basel­ga’s con­tro­ver­sial ex­it

It’s official. Memorial Sloan Kettering has picked a brain cancer expert as its new physician-in-chief and CMO, replacing José Baselga, who left under a cloud after being singled out by The New York Times and ProPublica for failing to properly air his lucrative industry ties.

His replacement, who now will be in charge of MSK’s cutting-edge research work as well as the cancer care delivered by hundreds of practitioners, is Lisa M. DeAngelis. DeAngelis had been chair of the neurology department and co-founder of MSK’s brain tumor center and was moved in to the acting CMO role in the wake of Baselga’s departure.

Penn team adapts CAR-T tech, reengi­neer­ing mouse cells to treat car­diac fi­bro­sis

After establishing itself as one of the pioneer research centers in the world for CAR-T cancer therapies, creating new attack vehicles to eradicate cancer cells, a team at Penn Medicine has begun the tricky transition of using the basic technology for heart repair work.

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Tal Zaks. Moderna

The mR­NA uni­corn Mod­er­na has more ear­ly-stage hu­man da­ta it wants to show off — reach­ing new peaks in prov­ing the po­ten­tial

The whole messenger RNA field has attracted billions of dollars in public and private investor cash gambled on the prospect of getting in on the ground floor. And this morning Boston-based Moderna, one of the leaders in the field, wants to show off a few more of the cards it has to play to prove to you that they’re really in the game.

The whole hand, of course, has yet to be dealt. And there’s no telling who gets to walk with a share of the pot. But any cards on display at this point — especially after being accused of keeping its deck under lock and key — will attract plenty of attention from some very wary, and wired, observers.

“In terms of the complexity and unmet need,” says Tal Zaks, the chief medical officer, “this is peak for what we’ve accomplished.”

Moderna has two Phase I studies it wants to talk about now.

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Sanofi takes a $260M hit to ex­tri­cate it­self from a dis­as­trous al­liance with Lex­i­con

Sanofi spent $300 million in cash to get into a $1.7 billion alliance with Lexicon on their SGLT1/2 diabetes drug sotagliflozin. And now that the drug has been spurned by the FDA after burning through a program that provided mixed late-stage data and a late shot at a last-place finish, the French pharma giant is forking over another $260 million to get out of the deal.

Sanofi’s unhappiness was already apparent when the company — now under new CEO Paul Hudson — posted a statement back in July that they were dropping the deal. But it wasn’t that simple. 

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Rit­ter bombs fi­nal PhI­II for sole lac­tose in­tol­er­ance drug — shares plum­met

More than two years ago Ritter Pharmaceuticals managed to find enough silver lining in its Phase IIb/III study — after missing the top-line mark — to propel its lactose intolerance toward a confirmatory trial. But as it turned out, the enthusiasm only set the biotech and its investors up to be sorely disappointed.

This time around there’s little left to salvage. Not only did RP-G28 fail to beat placebo in reducing lactose intolerance symptoms, patients in the treatment group actually averaged a smaller improvement. On a composite score measuring symptoms like abdominal pain, cramping, bloating and gas, patients given the drug had a mean reduction of 3.159 while the placebo cohort saw a 3.420 drop on average (one-sided p-value = 0.0106).

Ear­ly snap­shot of Ad­verum's eye gene ther­a­py sparks con­cern about vi­sion loss

An early-stage update on Adverum Biotechnologies’ intravitreal gene therapy has triggered investor concern, after patients with wet age-related macular degeneration (AMD) saw their vision deteriorate, despite signs that the treatment is improving retinal anatomy.

Adverum, on Wednesday, unveiled 24-week data from the OPTIC trial of its experimental therapy, ADVM-022, in six patients who have been administered with one dose of the therapy. On average, patients in the trial had severe disease with an average of 6.2 anti-VEGF injections in the eight months prior to screening and an average annualized injection frequency of 9.3 injections.

Alex Ar­faei trades his an­a­lyst's post for a new role as biotech VC; Sanofi vet heads to Vi­for

Too often, Alex Arfaei arrived too late. 

An analyst at BMO Capital Markets, he’d meet with biotech or pharmaceutical heads for their IPO or secondary funding and his brain, trained on a biology degree and six years at Merck and Endo, would spring with questions: Why this biomarker? Why this design? Why not this endpoint? Not that he could do anything about it. These execs were coming for clinical money; their decisions had been made and finalized long ago.