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.”

Hal Barron, GSK

Break­ing the death spi­ral: Hal Bar­ron talks about trans­form­ing the mori­bund R&D cul­ture at GSK in a crit­i­cal year for the late-stage pipeline

Just ahead of GlaxoSmithKline’s Q2 update on Wednesday, science chief Hal Barron is making the rounds to talk up the pharma giant’s late-stage strategy as the top execs continue to woo back a deeply skeptical investor group while pushing through a whole new R&D culture.

And that’s not easy, Barron is quick to note. He told the Financial Times:

I think that culture, to some extent, is as hard, in fact even harder, than doing the science.

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Aca­dia is mak­ing the best of it, but their lat­est PhI­II Nu­plazid study is a bust

Acadia’s late-stage program to widen the commercial prospects for Nuplazid has hit a wall. The biotech reported that their Phase III ENHANCE trial flat failed. And while they $ACAD did their best to cherry pick positive data wherever they can be found, this is a clear setback for the biotech.

With close to 400 patients enrolled, researchers said the drug flunked the primary endpoint as an adjunctive therapy for patients with an inadequate response to antipsychotic therapy. The p-value was an ugly 0.0940 on the Positive and Negative Syndrome Scale, which the company called out as a positive trend.

Their shares slid 12% on the news, good for a $426 million hit on a $3.7 billion market cap at close.

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Some Big Phar­mas stepped up their game on da­ta trans­paren­cy — but which flunked the test?

The nonprofit Bioethics International has come out with their latest scorecard on data transparency among the big biopharmas in the industry — flagging a few standouts while spotlighting some laggards who are continuing to underperform.

Now in its third year, the nonprofit created a new set of standards with Yale School of Medicine and Stanford Law School to evaluate the track record on trial registration, results reporting, publication and data-sharing practice.

Busy Gilead crew throws strug­gling biotech a life­line, with some cash up­front and hun­dreds of mil­lions in biobucks for HIV deal

Durect $DRRX got a badly needed shot in the arm Monday morning as Gilead’s busy BD team lined up access to its extended-release platform tech for HIV and hepatitis B.

Gilead, a leader in the HIV sector, is paying a modest $25 million in cash for the right to jump on the platform at Durect, which has been using its technology to come up with an extended-release version of bupivacaine. The FDA rejected that in 2014, but Durect has been working on a comeback.

In­tec blitzed by PhI­II flop as lead pro­gram fails to beat Mer­ck­'s stan­dard com­bo for Parkin­son’s

Intec Pharma’s $NTEC lead drug slammed into a brick wall Monday morning. The small-cap Israeli biotech reported that its lead program — coming off a platform designed to produce a safer, more effective oral drug for Parkinson’s — failed the Phase III at the primary endpoint.

Researchers at Intec, which has already seen its share price collapse over the past few months, says that its Accordion Pill-Carbidopa/Levodopa failed to prove superior to Sinemet in reducing daily ‘off’ time. 

Cel­gene racks up third Ote­zla ap­proval, heat­ing up talks about who Bris­tol-My­ers will sell to

Whoever is taking Otezla off Bristol-Myers Squibb’s hands will have one more revenue stream to boast.

The drug — a rising star in Celgene’s pipeline that generated global sales of $1.6 billion last year — is now OK’d to treat oral ulcers associated with Behçet’s disease, a common symptom for a rare inflammatory disorder. This marks the third FDA approval for the PDE4 inhibitor since 2014, when it was greenlighted for plaque psoriasis and psoriatic arthritis.

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Francesco De Rubertis

Medicxi is rolling out its biggest fund ever to back Eu­rope's top 'sci­en­tists with strange ideas'

Francesco De Rubertis built Medicxi to be the kind of biotech venture player he would have liked to have known back when he was a full time scientist.

“When I was a scientist 20 years ago I would have loved Medicxi,’ the co-founder tells me. It’s the kind of place run by and for investigators, what the Medicxi partner calls “scientists with strange ideas — a platform for the drug hunter and scientific entrepreneur. That’s what I wanted when I was a scientist.”

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Af­ter a decade, Vi­iV CSO John Pot­tage says it's time to step down — and he's hand­ing the job to long­time col­league Kim Smith

ViiV Healthcare has always been something unique in the global drug industry.

Owned by GlaxoSmithKline and Pfizer — with GSK in the lead as majority owner — it was created 10 years ago in a time of deep turmoil for the field as something independent of the pharma giants, but with access to lots of infrastructural support on demand. While R&D at the mother ship inside GSK was souring, a razor-focused ViiV provided a rare bright spot, challenging Gilead on a lucrative front in delivering new combinations that require fewer therapies with a more easily tolerated regimen.

They kept a massive number of people alive who would otherwise have been facing a death sentence. And they made money.

And throughout, John Pottage has been the chief scientific and chief medical officer.

Until now.

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Vlad Coric (Biohaven)

In an­oth­er dis­ap­point­ment for in­vestors, FDA slaps down Bio­haven’s re­vised ver­sion of an old ALS drug

Biohaven is at risk of making a habit of disappointing its investors.

Late Friday the biotech $BHVN reported that the FDA had rejected its application for riluzole, an old drug that they had made over into a sublingual formulation that dissolves under the tongue. According to Biohaven, the FDA had a problem with the active ingredient used in a bioequivalence study back in 2017, which they got from the Canadian drugmaker Apotex.

Apotex, though, has been a disaster ground. The manufacturer voluntarily yanked the ANDAs on 31 drugs — in late 2017 — after the FDA came across serious manufacturing deficiencies at their plants in India. A few days ago, the FDA made it official.

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