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.”

Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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Douglas Fambrough, Dicerna CEO (Boehringer Ingelheim via YouTube)

Roche-backed Dicer­na push­es in­to the pack rac­ing to­ward the block­buster hep B goal line, armed with PhI da­ta

Dicerna has lined up a set of proof-of-concept data from a small cohort of hepatitis B patients in a match-up against some heavyweight rivals which got out in front of this race. And right in the front row you’ll find a team from Roche, which paid $200 million in cash and offered another $1.5 billion in milestones to partner with Dicerna $DRNA on their RNAi program for hep B.

Right now it’s looking competitive, with lots of big challenges ahead.

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Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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Ab­b­Vie aban­dons a pi­o­neer­ing CRISPR R&D al­liance with Ed­i­tas as Brent Saun­der­s' deal is cast out

A little more than 3 years ago Allergan paid $90 million in a cash upfront to partner with gene editing player Editas on a CRISPR alliance focused on the eye. The lead program centered on LCA10, a rare, inherited retinal degenerative disease that appears in childhood and leads to blindness.

Allergan then went to AbbVie $ABBV in a buyout, and the pharma giant has no interest in moving forward on the gene editing front. The company punted it all back to Editas Thursday, with the biotech $EDIT noting in a statement after the market closed Thursday that it is regaining all rights for its ocular medicines, including EDIT-101.

President Trump speaks with members of the media before boarding Marine One (AP Images)

'Oc­to­ber is com­ing,' and every­one still wants to know if a Covid-19 vac­cine will be whisked through the FDA ahead of the elec­tion

Right on the heels of a lengthy assurance from FDA commissioner Stephen Hahn that the agency will not rush through a quick approval for a Covid-19 vaccine, the President of the United States has some thoughts on timing he’d like to share.

In an exchange with Fox News’ Geraldo Rivera on Thursday, President Trump allowed that a vaccine could be ready to roll “sooner than the end of the year, could be much sooner.”

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Lund­beck sounds taps on an­oth­er CNS drug, re­treat­ing from a mine field still oc­cu­pied by a Mer­ck team

Lundbeck has snipped another clinical-stage branch of its CNS research, dumping a schizophrenia program after determining that their therapy would have no positive influence on the disease.

Designed originally as a 240-patient study, researchers set out in early 2019 to see if a homegrown drug dubbed Lu AF11167 could make it through a proof-of-concept study. The drug is a PDE10Ai inhibitor, targeting an enzyme which it said at the time offered a new pathway to retuning the body’s neurotransmitter dopamine. The big idea was that by hitting their target, the drug would modulate “dopamine D1 and D2 receptor-mediated intraneuronal signaling without binding to these receptors,” influencing negative symptoms of schizophrenia.

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Le­vo Ther­a­peu­tics miss­es pri­ma­ry end­point in PhI­II tri­al of Prad­er-Willi drug — the lat­est set­back in a dis­as­ter-prone field

Marking yet another setback in the Prader-Willi Syndrome field, Levo Therapeutics failed to hit its primary endpoint in a Phase III study of intranasal carbetocin. But the biotech is now shifting its focus to the secondary endpoints in an effort to pluck victory out of the jaws of defeat.

The disorder, characterized by a false sense of starvation, is caused by the absence or deletion of a father’s chromosome 15. Illinois-based Levo’s potential therapy involves a selective oxytocin-receptor agonist.

Leonard Schleifer (AP Images)

Re­gen­eron adds more pos­i­tive PhI­II da­ta for its NGF pro­gram — but safe­ty is still a big con­cern

Two years after fasinumab hit its first late-stage bar, Regeneron is standing by its “high-risk, high reward” bet on the NGF antibody. But while new Phase III data solidified the potential reward, the risk is still threatening to blow it all up.

Regeneron execs and analysts alike now have their eyes set on a rival drug from Pfizer and Eli Lilly, whose fate at the FDA will likely set the scene for the class.