New analy­sis shows in­clisir­an con­sis­ten­cy in LDL-C re­duc­tion as No­var­tis read­ies for FDA de­ci­sion

As the FDA con­tin­ues its re­view of the for­mer-The Med­i­cines Com­pa­ny, now-No­var­tis can­di­date in­clisir­an ahead of an ex­pect­ed PDU­FA be­fore the year is out, the Swiss phar­ma re­leased pooled da­ta that it hopes bol­sters the case for ap­proval.

A post-hoc analy­sis of two Phase III in­clisir­an tri­als showed con­sis­ten­cy in ef­fi­ca­cy and safe­ty among pa­tients with both hy­per­lipi­demia and ath­er­o­scle­rot­ic car­dio­vas­cu­lar dis­ease de­spite statin ther­a­py, with 99% of pa­tients show­ing greater than 30% place­bo-ad­just­ed re­duc­tion in LDL-C lev­els. The av­er­age re­duc­tion was 54.1% from base­line in the 2,300 in­di­vid­u­als be­tween the two stud­ies.

The analy­sis mea­sured the can­di­date’s pro­file af­ter 17 months of the first dose. Around 88% of pa­tients hit 50% re­duc­tion of LDL-C in at least one point dur­ing the study, and af­ter the 17-month pe­ri­od, al­most two-thirds of pa­tients (66.4%) had a 50% re­duc­tion com­pared to 2.5% per­cent in the place­bo group.

Da­ta for the study were tak­en from the ORI­ON-10 tri­al, look­ing at hy­per­lipi­demia, and the ORI­ON-11 tri­al, ex­am­in­ing AS­CVD. In­clisir­an hit pri­ma­ry end­points of 52% and 50% LDL-C re­duc­tion, re­spec­tive­ly, at 17 months.

In­clisir­an works dif­fer­ent­ly than the big-name LDL-C drugs on the mar­ket, such as Am­gen’s Repatha and Sanofi/Re­gen­eron’s Pralu­ent. While those are mon­o­clon­al an­ti­bod­ies that in­hib­it the PC­SK9 pro­tein, in­clisir­an is a small in­ter­fer­ing RNA that works to pre­vent PC­SK9 from be­ing syn­the­sized in the liv­er.

Though those drugs have set the mar­ket pace since their ap­provals in 2015 with their ef­fi­ca­cy lev­els, they dis­ap­point­ed out of the gate thanks to stick­er shock at the ini­tial prices of around $14,000. The drug­mak­ers have since cut prices by about 60% though, mak­ing it tough for in­clisir­an to el­bow its way in­to the com­pet­i­tive field.

No­var­tis is bank­ing on added con­ve­nience, how­ev­er, as a way to mar­ket in­clisir­an should it re­ceive FDA ap­proval as doc­tors on­ly need to ad­min­is­ter the com­pound twice a year, fol­low­ing an ini­tial dose and a sec­ond dose three months lat­er. Repatha and Pralu­ent re­quire dos­ing ei­ther every two weeks or once a month.

In­clisir­an was large­ly seen as the big prize for No­var­tis when it ac­quired The Med­i­cines Com­pa­ny for $9.7 bil­lion last No­vem­ber. Though No­var­tis ad­mit­ted in doc­u­ments that the biotech like­ly wasn’t worth the $90 per share it was of­fer­ing, the phar­ma de­cid­ed to hon­or the ini­tial price hop­ing to cash in on the drug.

The FDA is ex­pect­ed to reach a de­ci­sion on in­clisir­an be­fore the end of 2020 in the treat­ment for hy­per­lipi­demia among adults who are on a max­i­mal­ly tol­er­at­ed dose of statin ther­a­py. It is al­so un­der re­view by the EMA.

Biogen CEO Michel Vounatsos (via Getty Images)

With ad­u­canum­ab caught on a cliff, Bio­gen’s Michel Vounatsos bets bil­lions on an­oth­er high-risk neu­ro play

With its FDA pitch on the Alzheimer’s drug aducanumab hanging perilously close to disaster, Biogen is rolling the dice on a $3.1 billion deal that brings in commercial rights to one of the other spotlight neuro drugs in late-stage development — after it already failed its first Phase III.

The big biotech has turned to Sage Therapeutics for its latest deal, close to a year after the crushing failure of Sage-217, now dubbed zuranolone, in the MOUNTAIN study.

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As­traZeneca, Ox­ford on the de­fen­sive as skep­tics dis­miss 70% av­er­age ef­fi­ca­cy for Covid-19 vac­cine

On the third straight Monday that the world wakes up to positive vaccine news, AstraZeneca and Oxford are declaring a new Phase III milestone in the fight against the pandemic. Not everyone is convinced they will play a big part, though.

With an average efficacy of 70%, the headline number struck analysts as less impressive than the 95% and 94.5% protection that Pfizer/BioNTech and Moderna have boasted in the past two weeks, respectively. But the British partners say they have several other bright spots going for their candidate. One of the two dosing regimens tested in Phase III showed a better profile, bringing efficacy up to 90%; the adenovirus vector-based vaccine requires minimal refrigeration, which may mean easier distribution; and AstraZeneca has pledged to sell it at a fraction of the price that the other two vaccine developers are charging.

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The ad­u­canum­ab co­nun­drum: The PhI­II failed a clear reg­u­la­to­ry stan­dard, but no one is cer­tain what that means any­more at the FDA

Eighteen days ago, virtually all of the outside experts on an FDA adcomm got together to mug the agency’s Billy Dunn and the Biogen team when they presented their upbeat assessment on aducanumab. But here we are, more than 2 weeks later, and the ongoing debate over that Alzheimer’s drug’s fate continues unabated.

Instead of simply ruling out any chance of an approval, the logical conclusion based on what we heard during that session, a series of questionable approvals that preceded the controversy over the agency’s recent EUA decisions has come back to haunt the FDA, where the power of precedent is leaving an opening some experts believe can still be exploited by the big biotech.

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John Maraganore, Alnylam CEO (Scott Eisen/Bloomberg via Getty Images)

Al­ny­lam gets the green light from the FDA for drug #3 — and CEO John Maraganore is ready to roll

Score another early win at the FDA for Alnylam.

The FDA put out word today that the agency has approved its third drug, lumasiran, for primary hyperoxaluria type 1, better known as PH1. The news comes just 4 days after the European Commission took the lead in offering a green light.

An ultra rare genetic condition, Alnylam CEO John Maraganore says there are only some 1,000 to 1,700 patients in the US and Europe at any particular point. The patients, mostly kids, suffer from an overproduction of oxalate in the liver that spurs the development of kidney stones, right through to end stage kidney disease.

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Jason Kelly, Ginkgo Bioworks CEO (Kyle Grillot/Bloomberg via Getty Images)

Af­ter Ko­dak de­ba­cle, US lends $1.1B to a syn­thet­ic bi­ol­o­gy com­pa­ny and their big Covid-19, mR­NA plans

In mid-August, as Kodak’s $765 million government-backed push into drug manufacturing slowly fell apart in national headlines, Ginkgo Bioworks CEO Jason Kelly got a message from his company’s government liaison: HHS wanted to know if they, too, might want a loan.

The government’s decision to lend Kodak three quarters of a billion dollars raised eyebrows because Kodak had never made drugs before. But Ginkgo, while not a manufacturing company, had spent the last decade refining new ways to produce materials inside cells and building automated facilities across Boston.

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Leonard Schleifer, Regeneron CEO (Andrew Harnik/AP)

Trail­ing Eli Lil­ly by 12 days, Re­gen­eron gets the FDA OK for their Covid-19 an­ti­body cock­tail

A month and a half after becoming the experimental treatment of choice for a newly diagnosed president, Regeneron’s antibody cocktail has received emergency use authorization from the FDA. It will be used to treat non-hospitalized Covid-19 patients who are at high-risk of progressing.

Although the Rgeneron drug is not the first antibody treatment authorized by the FDA, the news comes as a significant milestone for a company and a treatment scientists have watched closely since the outbreak began.

Bahija Jallal (file photo)

TCR pi­o­neer Im­muno­core scores a first with a land­mark PhI­II snap­shot on over­all sur­vival for a rare melanoma

Bahija Jallal’s crew at TCR pioneer Immunocore says they have nailed down a promising set of pivotal data for their lead drug in a frontline setting for a solid tumor. And they are framing this early interim readout as the convincing snapshot they need to prove that their platform can deliver on a string of breakthrough therapies now in the clinic or planned for it.

In advance of the Monday announcement, Jallal and R&D chief David Berman took some time to walk me through the first round of Phase III data for their lead TCR designed to treat rare, frontline cases of metastatic uveal melanoma that come with a grim set of survival expectations.

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FDA hands Liq­uidia and Re­vance a CRL and de­fer­ral, re­spec­tive­ly, as Covid-19 cre­ates in­spec­tion chal­lenge

Two biotechs said they got turned away by the FDA on Wednesday, in part due to pandemic-related travel restrictions.

North Carolina-based Liquidia Technologies was handed a CRL for its lead pulmonary arterial hypertension drug, citing the need for more CMC data and on-site pre-approval inspections, which the FDA hasn’t been able to conduct due to travel restrictions. The agency also deferred its decision on Revance Therapeutics’ BLA for its frown line treatment, because it needs to inspect the company’s northern California manufacturing facility. The action, Revance emphasized, was not a CRL.

Vivek Ramaswamy (Jeff Rumans/JPM 2020)

Urovan­t's lead drug dis­ap­points in mid-stage study as first big FDA de­ci­sion looms

Just as Urovant gets ready for its first big FDA decision on vibegron, the drug has flopped in what would’ve been a follow-on indication.

In a Phase IIa trial involving women with abdominal pain due to irritable bowel syndrome, vibegron failed to meet the bar on improving “average worst abdominal pain” over 12 weeks, compared to placebo, among IBS-D patients.

There were actually slightly more responders in the placebo group than in the drug arm, with only 40.9% of those randomized to vigebron achieving at least a 30% decrease in “worst abdominal pain” in the past 24 hours. The trial enrolled 222 women but only 189 completed the study.