FDA in-house re­view spot­lights an is­sue with one of Hori­zon's end­points but notes ef­fi­ca­cy for lead drug

The FDA in-house re­view high­lights a dis­agree­ment of in­ves­ti­ga­tors’ use of a key end­point by Hori­zon Phar­ma in the late-stage tri­al for the top drug in its pipeline, but large­ly agreed that the an­ti­body was ef­fec­tive.

Hori­zon sub­mit­ted a BLA for thy­roid eye dis­ease (TED) drug tepro­tu­mum­ab in March, less than two years af­ter they bought the drug (and the rest of a di­vi­sion) from Nar­row Riv­er for $145 mil­lion up­front. With break­through sta­tus, pri­or­i­ty re­view, or­phan des­ig­na­tion and in-house sales pro­jec­tions of up to $750 mil­lion, the one-time Roche re­ject be­came the mar­quee pipeline as­set for a com­pa­ny that’s de­vel­oped some of the world’s most ex­pen­sive drugs.

Hori­zon sub­mit­ted their ap­pli­ca­tion based on a Phase II and a Phase III study, tout­ing pos­i­tive re­sults on pri­ma­ry end­points in both tri­als. But the FDA re­ject­ed their pri­ma­ry end­point in the Phase II and sec­ondary end­point in Phase III: Clin­i­cal Ac­tiv­i­ty Score, or CAS. They not­ed that CAS com­piles mul­ti­ple forms of clin­i­cal ac­tiv­i­ty and weighs them equal­ly.

“FDA’s clin­i­cal team does not con­sid­er these fac­tors to be of equal clin­i­cal weight ei­ther to the pa­tients or to physi­cians treat­ing these pa­tients,” they wrote.

Rather, they fo­cused on pa­tients’ re­sponse in prop­to­sis, or the dis­lo­ca­tion of the eye from its or­bit, ar­gu­ing that this was the main symp­tom that af­flicts TED pa­tients. They not­ed an im­prove­ment by week 6 in both tri­als that con­tin­ued through the treat­ment pe­ri­od, and that 60% of pa­tients did not re­lapse in the year fol­low­ing treat­ment.

For pa­tients, prop­to­sis of­ten leads to diplop­ia — more pop­u­lar­ly called “dou­ble-vi­sion” — and de­spite less than eye-pop­ping re­sults in pa­tients’ sub­jec­tive re­spons­es, the FDA said Hori­zon showed im­prove­ment.

The FDA had few warn­ings about ad­verse ef­fects be­sides a slight in­crease in gas­tro-in­testi­nal events, but not­ed the lim­it­ed pa­tient pop­u­la­tion. With less than 90 pa­tients who re­ceived the treat­ment, they said, ad­verse ef­fects can be ex­pect­ed to oc­cur in up to 3% of pa­tients with­out show­ing up in the tri­al.

TED is an au­toim­mune dis­or­der that large­ly af­fects women in mid­dle age and can lead to blind­ness if not treat­ed with surgery ear­ly on. Hori­zon projects to treat around 15,000 to 20,000 peo­ple.

Tim­o­thy Wal­bert Hori­zon

The PDU­FA date is set for March 8. An ap­proval would mark one end of a long road for the drug. It be­gan at Gen­mab, be­fore Roche li­censed it as a treat­ment for sol­id tu­mors. It proved in­ef­fec­tive, and was lat­er test­ed at Nar­row Riv­er in di­a­bet­ic mac­u­lar ede­ma — the an­ti­body af­fects the in­sulin-like growth fac­tor-1 re­cep­tor — be­fore show­ing promise in TED.

In their lat­est earn­ings call on Sep­tem­ber 30, the com­pa­ny ap­peared to ful­ly ex­pect ap­proval.

“We are ag­gres­sive­ly prepar­ing for the po­ten­tial US launch with our tepro­tu­mum­ab com­mer­cial and med­ical teams ful­ly in place,” CEO Tim­o­thy Wal­bert said.

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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Covid-19 roundup: J&J and BAR­DA agree to $1 bil­lion for 100 mil­lion dos­es; Plas­ma re­duces mor­tal­i­ty by 50% — re­ports

J&J has become the latest vaccine developer to agree to supply BARDA with doses of their Covid-19 vaccine, signing an agreement that will give the government 100 million doses in exchange for $1 billion in funding.

The agreement, similar to those signed by Novavax, Sanofi and AstraZeneca-Oxford, provides funding not only for individual doses but to help J&J ramp up manufacturing. Pfizer, by contrast, received $1.95 billion for the doses alone. Still, if one looked at each agreement as purchase amounts, J&J’s deal would be $10 per dose, slotting in between Novavax’s $16 per dose and AstraZeneca’s $4 per dose.

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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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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.

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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