In a turf war with Eli Lil­ly, No­vo Nordisk steps off with pos­i­tive PhI­II for its chal­leng­ing oral GLP-1 drug

Just a cou­ple of months af­ter No­vo Nordisk shook up the big di­a­betes mar­ket with the ar­rival of its GLP-1 drug Ozem­pic (semaglu­tide) in the US, the big Dan­ish com­pa­ny has be­gun rolling out the first in a long line­up of Phase III stud­ies for its next-gen oral ver­sion of the drug. And the de­but of the Phase III da­ta start­ed out on a pos­i­tive note.

Mads Krogs­gaard Thom­sen

Re­searchers for No­vo say that the first of 10 Phase III stud­ies that read out this year came with sta­tis­ti­cal­ly sig­nif­i­cant re­sults on all three dos­es test­ed. And if they can stay on track, they plan to field the first ever oral GLP-1 to reg­u­la­tors in 2019, vow­ing to com­mand an even big­ger share of the mega block­buster mar­ket af­ter over­com­ing some huge hur­dles in de­vel­op­ing an oral pep­tide ther­a­py.

Here’s the break­down. No­vo test­ed three dos­es in this first study: 3, 7 and 14 mg.

Those three dos­es pro­duced re­duc­tions in HbA1c of 0.8%, 1.3% and 1.5%, push­ing di­a­bet­ics be­low the crit­i­cal 7.0% mark by 59%, 72% and 80% of pa­tients. And they lost weight, av­er­ag­ing cuts of 1.7 kg, 2.5 kg and 4.1 kg — though on­ly that high dose re­sponse was sta­tis­ti­cal­ly sig­nif­i­cant.

Eli Lil­ly is al­ready man­ning the de­fens­es in the bat­tle for mar­ket share in­volv­ing the in­jectable GLP-1s, with No­vo com­ing at them with da­ta to prove that semaglu­tide is bet­ter than Trulic­i­ty. And an­a­lysts are now pay­ing rapt at­ten­tion to these new oral da­ta points. If No­vo can achieve rough­ly the same re­spons­es with a pill to re­place an in­jec­tion, they feel that they can more ef­fec­tive­ly yank away pa­tients from Eli Lil­ly.

But it’s not an easy task. Re­searchers have been work­ing on oral pep­tides for years, of­ten de­feat­ed by the storm of caus­tic en­zymes and acids that the body us­es to ab­sorb food, which leaves lit­tle bio-avail­abil­i­ty left.

In No­vo’s case, they are way out front with a drug that re­quires pa­tients to avoid eat­ing break­fast for about half an hour af­ter they take the pill. But they be­lieve it can still work with pa­tients.

Lil­ly ex­ecs, though, have been scoff­ing at the pills, say­ing they’re a crude at­tempt that of­fers an in­fe­ri­or so­lu­tion to di­a­bet­ics.

Jan Lund­berg

At the high dose, not­ed Lil­ly’s top sci­en­tist Jan Lund­berg a cou­ple of weeks ago, pep­tides are hin­dered “by a lot of nat­ur­al mech­a­nists, and we as­sume that the No­vo prod­uct on­ly has 1 or 2% bio-avail­abil­i­ty, which means that you lose most of the sub­stance. The dilem­ma al­so re­mains here about the need for hav­ing fast­ing and not eat­ing for some time af­ter you take this drug, be­cause then you have food in­ter­ac­tions, so it’s re­al­ly a sub­op­ti­mal oral agent. I think it would be so much bet­ter to have a more tra­di­tion­al small mol­e­cule for this re­cep­tor.”

And that’s what they’re work­ing on now, though the drug is still in pre­clin­i­cal re­search, far be­hind the No­vo work.

An­a­lysts are al­so keen­ly fol­low­ing the side ef­fects of this drug, par­tic­u­lar­ly the nau­sea that has been cit­ed be­fore. Ever­core ISI’s Umer Raf­fat not­ed:

We didn’t get full de­tails by arm, but press re­lease notes 5-16% of pts had nau­sea vs 6% in pbo.  To me, this sug­gests low­er dos­es are pbo-like.  And the 14 mg dose like­ly tracked in the mid-teens.  It’s high­er than pbo, but imho, man­age­able.  Again, even this nau­sea is­sue ties back to Pk man­age­ment via strin­gent pre- and post-dose fast­ing pe­ri­od and vol­ume of wa­ter etc.

No­vo Nordisk has been a dom­i­nant play­er in the di­a­betes mar­ket for years, with a sharp and pro­fes­sion­al R&D group well known for ham­mer­ing away at sci­en­tif­ic prob­lems un­til they are mas­tered and new drugs can be mar­ket­ed.

This group won’t back down, but nei­ther will Lil­ly.

“We are very en­cour­aged by the re­sults of the PI­O­NEER 1 tri­al, which con­firm the un­prece­dent­ed oral ef­fi­ca­cy of semaglu­tide that was re­port­ed in the Phase II clin­i­cal tri­al in type 2 di­a­betes,” said Mads Krogs­gaard Thom­sen, ex­ec­u­tive vice pres­i­dent and chief sci­ence of­fi­cer of No­vo Nordisk. “We look for­ward to pro­vid­ing da­ta from the re­main­ing nine PI­O­NEER tri­als through­out this year and an ex­pect­ed reg­u­la­to­ry sub­mis­sion in 2019.”

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.

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.

Endpoints News

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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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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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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.

Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.

Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.