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.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

UP­DAT­ED: Eli Lil­ly’s $1.6B can­cer drug failed to spark even the slight­est pos­i­tive gain for pa­tients in its 1st PhI­II

Eli Lilly had high hopes for its pegylated IL-10 drug pegilodecakin when it bought Armo last year for $1.6 billion in cash. But after reporting a few months ago that it had failed a Phase III in pancreatic cancer, without the data, its likely value has plunged. And now we’re getting some exact data that underscore just how little positive effect it had.

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Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

A few weeks ago, when Stephen Hahn was being lightly queried by Senators in his confirmation hearing as the new commissioner of the FDA, he made the usual vow to maintain the gold standard in drug development.

Neatly summarized, that standard requires the agency to sign off on clinical data — usually from two, well-controlled human studies — that prove a drug’s benefit outweighs any risks.

Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

That confirmatory trial the FDA demands can wait a few years. And most everyone in biopharma would tell you that’s the right thing for patients. They know its a tonic for everyone in the industry faced with pushing a drug through clinical development. And it’s helped inspire a global biotech boom.

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UP­DAT­ED: New play­ers are jump­ing in­to the scram­ble to de­vel­op a vac­cine as pan­dem­ic pan­ic spreads fast

When the CNN news crew in Wuhan caught wind of the Chinese government’s plan to quarantine the city of 11 million people, they made a run for one of the last trains out — their Atlanta colleagues urging them on. On the way to the train station, they were forced to skirt the local seafood market, where the coronavirus at the heart of a brewing outbreak may have taken root.

And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

The early reaction in the biotech industry has been classic, with small-cap companies scrambling to headline efforts to step in fast. But there are also new players in the field with new tech that has been introduced since the last of a series of pandemic panics that could change the usual storylines. And they’re volunteering for a crash course in speeding up vaccine development — a field where overnight solutions have been impossible to prove.

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