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.

BiTE® Plat­form and the Evo­lu­tion To­ward Off-The-Shelf Im­muno-On­col­o­gy Ap­proach­es

Despite rapid advances in the field of immuno-oncology that have transformed the cancer treatment landscape, many cancer patients are still left behind.1,2 Not every person has access to innovative therapies designed specifically to treat his or her disease. Many currently available immuno-oncology-based approaches and chemotherapies have brought long-term benefits to some patients — but many patients still need other therapeutic options.3

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

UP­DAT­ED: Es­ti­mat­ing a US price tag of $5K per course, remde­sivir is set to make bil­lions for Gilead, says key an­a­lyst

Data on remdesivir — the first drug shown to benefit Covid-19 patients in a randomized, controlled trial setting — may be murky, but its maker Gilead could reap billions from the sales of the failed Ebola therapy, according to an estimate by a prominent Wall Street analyst. However, the forecast, which is based on a $5,000-per-course US price tag, triggered the ire of one top drug price expert.

Gilead bol­sters its case for block­buster hope­ful fil­go­tinib as FDA pon­ders its de­ci­sion

Before remdesivir soaked up the spotlight amid the coronavirus crisis, Gilead’s filgotinib was the star experimental drug tapped to rake in billions competing with other JAK inhibitors made by rivals including AbbVie and Eli Lilly.

Now, long term data on the drug — discovered by Gilead’s partners at Galapagos and posted as part of a virtual medical conference — have solidified the durability and safety of filgotinib in patients with rheumatoid arthritis, spanning data from three late-stage trials. An FDA decision on the drug is expected this year.

Joseph Kim, Inovio CEO (Andrew Harnik, AP Images)

Caught in a stand­off with its con­tract man­u­fac­tur­er over Covid-19 vac­cine, In­ovio files suit in an at­tempt to break free while ri­vals race ahead

Inovio was one of the first vaccine developers to snag attention for a jab that their execs said promised to end the Covid-19 pandemic. Using their own unique DNA tech, CEO Joseph Kim said it took just 3 hours to work it out.

But while rivals are racing to the finish line with ambitious plans to make vast quantities of their vaccines with billions of dollars of deals, Inovio is still stuck at the starting line on manufacturing.

Covid-19 roundup: Mod­er­na read­ies to en­ter PhI­II in Ju­ly, As­traZeneca not far be­hind; EU ready to ne­go­ti­ate vac­cine ac­cess with $2.7B fund

Moderna may soon add another first to the Covid-19 vaccine race.

In March, the mRNA biotech was the first company to put a Covid-19 vaccine into humans. Next month, they may become the first company to put their vaccine into the large, late-stage trials that are needed to prove whether the vaccine is effective.

In an interview with JAMA editor Howard Bauchner, NIAID chief Anthony Fauci said that a 30,000-person, Phase III trial for Moderna’s vaccine could start in July. The news comes a week after Moderna began a Phase II study that will enroll several hundred people.

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