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.

George Scangos (L) and Marianne De Backer

Pi­o­neer­ing biotech icon George Scan­gos hands in his re­tire­ment pa­pers — and this time it’s for re­al

George Scangos, one of the all-time great biotech CEOs, says the time has come to turn over the reins one last time.

The 74-year-old biotech legend spent close to three decades in a CEO post. The first was at Exelixis — which is still heavily focused on a drug Scangos advanced in the clinic. The second “retirement” was at Biogen, where he and his team were credited with a big turnaround with the now fading MS blockbuster Tecfidera. And the third comes at Vir, where he traded in his Big Biotech credentials for a marquee founder’s role back on the West Coast, hammering out a Covid-19 alliance with Hal Barron — then R&D chief at GSK — and breaking new ground on infectious diseases with some high-powered venture players.

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Jeanne Loring, director of the Center for Regenerative Medicine (Credit: Jamie Scott Lytle)

A stem cell pi­o­neer sent an ex­per­i­ment in­to space. Pa­tients are the next fron­tier

Last July, Jeanne Loring stood on a dirt road surrounded by Florida swampland and watched as a nearby SpaceX rocket blasted into the sky. The payload included a very personal belonging: cell clusters mimicking parts of her brain.

For more than two decades, Loring has been at the forefront of a stem cell field that always seems on the brink of becoming the next thing in medicine, but has been slow to lift off.

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Pa­tient death spurs tri­al halt for Ma­gen­ta Ther­a­peu­tics

Magenta Therapeutics is pausing an early-stage clinical trial after a patient died. The death was deemed to be possibly related to its drug, MGTA-117.

The biotech said the pause of the Phase I/II trial is voluntary and gives it time to review all available data before deciding what to do next. It’s also reported the known information to the FDA.

The dose-escalation trial was designed to test whether MGTA-117, an antibody-drug conjugate, could serve as a more targeted alternative to high-intensity chemotherapy as a conditioning agent for cancer patients who are set to receive a stem cell transplant. It recruited patients with relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome.

FDA re­ports ini­tial 'no sig­nal' for stroke risk with Pfiz­er boost­ers, launch­es con­comi­tant flu shot study

The FDA hasn’t detected any potential safety signals, including for stroke, in people aged 65 years and older who have received Pfizer’s bivalent Covid booster, one senior official told members of the agency’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on Thursday.

The update comes as the FDA and CDC investigate a “preliminary signal” that may indicate an increased risk of ischemic stroke in older Americans who received Pfizer’s updated shot.

Bris­tol My­ers claims win with CAR-T ther­a­py Breyanzi in leukemia

Bristol Myers Squibb is looking to expand Breyanzi into more indications — and the pharma’s newest data readout makes progress on that front.

The Big Pharma put out word Thursday that the CAR-T cell therapy met the primary endpoint of complete response rate compared to historical control in a subset of patients with relapsed or refractory chronic lymphocytic leukemia (CLL) that were refractory to a BTK inhibitor and pretreated with a BCL-2 inhibitor.

FDA cuts off use for As­traZeneca’s Covid-19 ther­a­py Evusheld

The FDA has stopped use of another drug as a result of the new coronavirus variants. On Thursday, the agency announced that AstraZeneca’s antibody combo Evusheld, which was an important prevention option for many immunocompromised people and others, is no longer authorized.

The FDA said it made its decision based on the fact that Evusheld works on fewer than 10% of circulating variants.

Evusheld was initially given emergency authorization at the end of 2021. However, as Omicron emerged, so did studies that showed Evusheld might not work against the dominant Omicron strain. In October, the FDA warned healthcare providers that Evusheld was useless against the Omicron subvariant BA.4.6. It followed that up with another announcement earlier this month that it did not think Evusheld would work against the latest Omicron subvariant XBB.1.5.

In­vestor 'misalign­men­t' leads to tR­NA biotech's shut­ter­ing

A small biotech looking to carve a lane in the tRNA field has folded, an investor and a co-founder confirmed to Endpoints News.

Similar to Flagship’s Alltrna and other upstarts like Takeda-backed hC Bioscience, the now-shuttered Theonys was attempting to go after transfer RNA, seen as a potential Swiss Army knife in the broader RNA therapeutics space. The idea is that one tRNA drug could be used across a galaxy of disorders and diseases.

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Vu Truong, Aridis Pharmaceuticals CEO (Aridis/Nasdaq)

Aridis' mon­o­clon­al an­ti­body fails PhI­II, but plans for sec­ond tri­al any­way

Aridis Pharmaceuticals’ monoclonal antibody missed the bar in a Phase III test in ventilator-associated pneumonia caused by the gram-positive bacteria S. aureus, the company announced Wednesday. 

But Aridis is planning for a second Phase III study anyway once it discusses the findings with the FDA and the European Medicines Agency. Execs blamed recruitment challenges stemming from Covid-19 and Russia’s invasion of Ukraine for the miss, cutting their enrollment target in half.

Al Gianchetti, XyloCor CEO

Xy­lo­Cor wraps up PhII for heart dis­ease gene ther­a­py, plans for piv­otal tri­al

XyloCor Therapeutics says patients with heart disease who got its gene therapy could exercise for longer and had fewer chest pain attacks. The biotech announced it completed a Phase I/II trial of the gene therapy Thursday morning, and plans to move forward with a pivotal trial.

In the Phase II portion of the trial, 28 patients with angina (or chest pain) caused by coronary artery disease and who had no other treatment options were enrolled and were given the highest tested dose from the first part of the trial. Patients were followed for six months.