Ab­b­Vie, J&J block­buster Im­bru­vi­ca rakes in 11th FDA ap­proval, as com­peti­tors work on erod­ing fran­chise

Ab­b­Vie and J&J’s mar­ket-lead­ing Im­bru­vi­ca, the orig­i­nal BTK in­hibitor, con­tin­ues to rake in ap­provals, while com­pe­ti­tion in the class of drugs heats up.

On Tues­day, the drug se­cured its 11th FDA ap­proval. Im­bru­vi­ca in com­bi­na­tion with Roche’s rit­ux­imab has been sanc­tioned for use as the first line of de­fense in pa­tients with chron­ic lym­pho­cyt­ic leukemia (CLL) or small lym­pho­cyt­ic lym­phoma (SLL).

Im­bru­vi­ca in­hibits Bru­ton’s ty­ro­sine ki­nase (BTK), an en­zyme that plays a cru­cial role in onco­genic sig­nal­ing that is key for the pro­lif­er­a­tion and sur­vival of leukemic cells in many B-cell ma­lig­nan­cies. The block­buster drug was first ap­proved in 2013, but safe­ty and tol­er­a­bil­i­ty is­sues soon emerged. Since then, sec­ond-gen­er­a­tion BTK in­hibitors, such as As­traZeneca’s Calquence, have been po­si­tioned as safer but equal­ly ef­fi­ca­cious al­ter­na­tives.

In De­cem­ber, Chi­na-based BeiGene’s quest to over­shad­ow mar­ket-lead­ing Im­bru­vi­ca with its own BTK in­hibitor fell through af­ter a head-to-head study pit­ting the two ther­a­pies fa­vored the Ab­b­Vie/J&J drug in pa­tients with a rare form of lym­phoma.

How­ev­er, the safe­ty pro­file of BeiGene’s Brukin­sa did give it an edge in the open-la­bel study, caus­ing less atri­al fib­ril­la­tion and bleed­ing that could be clin­i­cal­ly and com­mer­cial­ly mean­ing­ful, SVB Leerink an­a­lyst Ge­of­frey Porges not­ed at the time.

Still, Porges stuck by his sales fore­cast for Im­bru­vi­ca — to grow from $4.7 bil­lion in 2019 to $7.7 bil­lion in 2022 to $8.9 bil­lion in 2024 to $10 bil­lion in 2026, be­fore los­ing ex­clu­siv­i­ty and erod­ing rapid­ly in the 2028-2031 pe­ri­od.

Ge­of­frey Porges SVB Leerink

“Our fore­cast as­sumes con­tin­ued dom­i­nance of the CLL in­di­ca­tion by Ab­b­Vie/JNJ’s Im­bru­vi­ca, with on­ly 30% share loss for Im­bru­vi­ca in CLL by 2024 and 33% by 2026,” he said. “Should zanubru­ti­nib con­firm bet­ter safe­ty (on atri­al fib­ril­la­tion and ma­jor he­m­or­rhage) com­pared to Im­bru­vi­ca in the CLL piv­otal tri­als, then the share loss for Im­bru­vi­ca could be greater than we cur­rent­ly fore­cast.”

The Im­bru­vi­ca+rit­ux­imab ap­proval for first-line CLL and SLL pa­tients was based on da­ta from the E1912 study, which test­ed the Im­bru­vi­ca regime against stan­dard-of-care treat­ment: the chemoim­munother­a­py reg­i­men of flu­dara­bine, cy­clophos­phamide and rit­ux­imab (FCR).

Bri­an Koff­man

Da­ta from the tri­al in­volv­ing 529 pre­vi­ous­ly un­treat­ed CLL pa­tients showed that af­ter 3 years, the per­cent­age of pa­tients with pro­gres­sion-free sur­vival was 89.4% in the Im­bru­vi­ca group, ver­sus with 72.9% in the chemoim­munother­a­py arm — meet­ing the main goal of the study. Da­ta on over­all sur­vival al­so fa­vored the Im­bru­vi­ca group at 98.8%, as com­pared with 91.5% in the chemoim­munother­a­py group, over the same time pe­ri­od.

“The gold-stan­dard first-line treat­ment op­tion for many pa­tients with chron­ic lym­pho­cyt­ic leukemia who were fit enough to tol­er­ate an ag­gres­sive treat­ment course had been the in­tra­venous chemoim­munother­a­py of FCR — that is, un­til to­day,” said Bri­an Koff­man, the CMO of the CLL So­ci­ety, in a state­ment.

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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Pascal Soriot (AP Images)

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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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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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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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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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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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.

Bax­ter con­tin­ues on-shoring push with $50M In­di­ana ex­pan­sion

It’s been a banner year for the once humdrum business of manufacturing drugs, particularly vaccines. Billions have been spent ramping up facilities for Covid-19 jabs, while individual CDMOs have expanded their facilities, apparently anticipating demand or responding to a government-led push to onshore drug manufacturing.

Now Baxter Biopharma Solutions, the CDMO wing of the many-armed healthcare giant Baxter, is getting in on the game. On Tuesday, they announced plans to spend $50 million to expand their flagship, 600,000 square-foot facility in Bloomington, IN.