As ri­vals march on, No­var­tis se­cures pri­or­i­ty FDA re­view for sick­le cell dis­ease ther­a­py

About a month af­ter ri­val Glob­al Blood Ther­a­peu­tics $GBT un­veiled pos­i­tive piv­otal da­ta on its sick­le cell dis­ease drug, No­var­tis’ $NVS ther­a­py for the blood dis­or­der has been grant­ed a speedy re­view by the FDA.

Vas Narasimhan

Tout­ed by No­var­tis chief Vas Narasimhan as a po­ten­tial block­buster, the Swiss drug­mak­er’s drug, crizan­l­izum­ab, in Jan­u­ary se­cured the FDA’s break­through ther­a­py des­ig­na­tion for its abil­i­ty to pre­vent de­bil­i­tat­ing­ly painful va­so-oc­clu­sive cri­sis (VOCs) for pa­tients af­fect­ed by the group of in­her­it­ed red blood cell dis­or­ders that typ­i­cal­ly af­flict those of African an­ces­try.

Sick­le cell dis­ease pa­tients have atyp­i­cal he­mo­glo­bin mol­e­cules, which can dis­tort red blood cells in­to a sick­le, or cres­cent, shape. Symp­toms such as ane­mia, re­peat­ed in­fec­tions and pe­ri­od­ic episodes of pain called va­so-oc­clu­sive crises (VOC) when sick­le-shaped red blood cells get stuck in­side blood ves­sels be­gin to ap­pear in ear­ly child­hood. These episodes de­prive the body of oxy­gen-rich blood, which can cul­mi­nate in wide­spread tis­sue and or­gan dam­age — par­tic­u­lar­ly in the lungs, kid­neys, spleen, heart and brain — and dras­ti­cal­ly di­min­ish life ex­pectan­cy.

For now, bone mar­row trans­plants of­fer the on­ly po­ten­tial cure for sick­le cell ane­mia — but the pro­ce­dure is not safe enough for pa­tients old­er than 16 — be­sides se­cur­ing a healthy donor is dif­fi­cult and the risks can be life-threat­en­ing. There­fore, treat­ment is typ­i­cal­ly lim­it­ed to avoid­ing crises, re­liev­ing symp­toms and pre­vent­ing com­pli­ca­tions. Hy­drox­yurea, a drug be­lieved to stim­u­late the pro­duc­tion of fe­tal he­mo­glo­bin, is of­ten giv­en dai­ly to re­duce the fre­quen­cy of painful crises — but it in­creas­es the risk of in­fec­tion, and the risks as­so­ci­at­ed with long-term use are un­clear.

No­var­tis’ mon­o­clon­al an­ti­body, called crizan­l­izum­ab or SEG101, is ad­min­is­tered in­tra­venous­ly and en­gi­neered to bind to a mol­e­cule called P-se­lectin, one of the ma­jor dri­vers of the va­so-oc­clu­sive process. No­var­tis gained ac­cess to the drug in 2016 via an ac­qui­si­tion of Se­lexys Phar­ma­ceu­ti­cals in a deal val­ued at up to $665 mil­lion.

The drug has shown to re­duce the me­di­an an­nu­al rate of VOCs lead­ing to health care vis­its, and an analy­sis of Phase II da­ta pre­sent­ed at the ASH con­fer­ence last year al­so showed that 35.8% of those giv­en the ex­per­i­men­tal treat­ment did not ex­pe­ri­ence a VOC, ver­sus 16.9% on the place­bo arm in pa­tients with a his­to­ry of 2-10 VOCs in the pre­ced­ing year. Af­ter ini­tial­ly sug­gest­ing a mar­ket­ing ap­pli­ca­tion would be sub­mit­ted in 2018, No­var­tis said it would make its case for the drug in 2019.

Last month, Glob­al Blood Ther­a­peu­tics said it was poised to sub­mit an ap­pli­ca­tion for ac­cel­er­at­ed ap­proval for its once-dai­ly pill vox­elo­tor — which is de­signed to work by in­creas­ing he­mo­glo­bin’s affin­i­ty for oxy­gen — in the sec­ond half of this year. Da­ta pre­sent­ed showed the drug con­ferred a sus­tained im­prove­ment in oxy­gen-rich he­mo­glo­bin lev­els, and was al­so as­so­ci­at­ed with few­er VOCs — a key sec­ondary end­point — but the dif­fer­ence wasn’t sta­tis­ti­cal­ly sig­nif­i­cant.

“While No­var­tis por­trays an ad­van­tage of po­ten­tial­ly hav­ing crizan­l­izum­ab ap­proved ahead of vox­elo­tor, we be­lieve vox­elo­tor has an edge on con­ve­nience. Ul­ti­mate­ly, we don’t view the drugs as di­rect com­peti­tors, but rather com­ple­men­tary treat­ments, giv­en both drugs show ben­e­fi­cial re­sults in dif­fer­ent mea­sures, and work through dif­fer­ent mech­a­nism of ac­tions,” Can­tor Fitzger­ald an­a­lyst El­e­mer Piros wrote in a note.

In 2017, Em­maus Life Sci­ences se­cured SCD ap­proval from the FDA for En­dari — a phar­ma­ceu­ti­cal ver­sion of L-glu­t­a­mine, a drug sold over-the-counter as a nu­tri­tion­al sup­ple­ment. EU reg­u­la­tors in con­trast re­cent­ly rec­om­mend­ed the drug not be ap­proved on the ba­sis that the da­ta from the main tri­al did not show it was ef­fec­tive at re­duc­ing the num­ber of sick­le cell crises or hos­pi­tal vis­its, and a high drop-out rate in the study.

GBT last Au­gust li­censed a P-se­lectin an­tag­o­nist, in­clacum­ab, from Roche. Oth­er drug­mak­ers, in­clud­ing blue­bird Bio $BLUE, Imara, and part­ners CRISPR Ther­a­peu­tics and Ver­tex $VRTX, are al­so work­ing on their own ther­a­pies. Pfiz­er $PFE and Gly­coMimet­ics $GLYC are test­ing their SCD drug, riv­ipansel, in an on­go­ing Phase III study.

In a note pub­lished in late June with com­men­tary from a key opin­ion leader, Cowen an­a­lysts laid out the po­ten­tial land­scape of SCD ther­a­pies.

“BLUE’s Lenti­Glo­bin showed im­pres­sive da­ta and has a po­ten­tial to be cu­ra­tive…GBT’s Vox­elo­tor needs more mean­ing­ful da­ta to prove re­al-world ef­fi­ca­cy and safe­ty. NVS’s crizan has com­pelling da­ta like­ly to gar­ner ap­proval in 18+ yo and PFE/GLYC’s Riv­ipansel Ph3 study de­sign has some el­e­ments that raise con­cerns, but might still be ap­prov­able.”

So­cial im­age: No­var­tis, AP Im­ages

Scott Gottlieb, AP Images

Scott Got­tlieb is once again join­ing a team that en­joyed good times at the FDA un­der his high-en­er­gy stint at the helm

Right after jumping on Michael Milken’s FasterCures board on Monday, the newly departed FDA commissioner is back today with news about another life sciences board post that gives him a ringside chair to cheer on a lead player in the real-world evidence movement — one with very close ties to the FDA.

Aetion is reporting this morning that Gottlieb is joining their board, a group that includes Mohamad Makhzoumi, a general partner at New Enterprise Associates, where Gottlieb returned after stepping out of his role at the FDA 2 years after he started.

Gottlieb — one of the best connected execs in biopharma — knows this company well. As head of FDA he championed the use of real-world evidence to help guide drug developers and the agency in gaining greater efficiencies, which helped set up Aetion as a high-profile player in the game.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Deborah Dunsire. Lundbeck

UP­DAT­ED: Deb­o­rah Dun­sire is pay­ing $2B for a chance to leap di­rect­ly in­to a block­buster show­down with a few of the world's biggest phar­ma gi­ants

A year after taking the reins as CEO of Lundbeck, Deborah Dunsire is making a bold bid to beef up the Danish biotech’s portfolio of drugs in what will likely be a direct leap into an intense rivalry with a group of giants now carving up a growing market for new migraine drugs.

Bright and early European time Monday morning the company announced that it will pay up to about $2 billion to buy Alder, a little biotech that is far along the path in developing a quarterly IV formulation of a CGRP drug aimed at cutting back the number of crippling migraines patients experience each month. In a followup call, Dunsire also noted that the company will likely need 200 to 250 reps for this marketing task on both sides of the Atlantic. And analysts were quick to note that the dealmaking at Lundbeck isn’t done, with another $2 billion to $3 billion available for more deals to beef up the pipeline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

San Diego cou­ple charged with steal­ing trade se­crets, open­ing Chi­nese biotech as DOJ crack­down con­tin­ues

A San Diego couple has been charged with stealing trade secrets from a US hospital and opening a business based off those secrets in China as the controversial industry-wide crackdown on alleged corporate espionage continues. On the same day, the Department of Justice announced they had arrested Beijing representative Zhongsan Liu for allegedly trying to obtain research visas for government recruiters.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Bio­gen pulls the plug on prized IPF drug from $562M+ Stromedix buy­out

One of Biogen’s attempts to branch out has flopped as the biotech scraps a mid-stage program for idiopathic pulmonary fibrosis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Warts for the win: Aclar­is' lead drug clears piv­otal study

Aclaris Therapeutics has found a way to get rid of the warts and all.

The company — which earlier this month decided to focus on its arsenal of kinase inhibitors — on Monday unveiled positive data from a pivotal study testing its lead experimental drug for use in common warts.

The drug, A-101, was tested in a 502-patient study called THWART-2 — patients enrolled had one to six warts before qualifying for the trial. Patients either self-administered A-101 topical solution or a vehicle twice a week over a two-month period. A higher proportion of patients on the drug (a potent hydrogen peroxide topical solution) saw their warts disappear at day 60, versus the vehicle (p<0.0001) — meeting the main goal of the study.  Each secondary endpoint also emerged in favor of A-101, the company said.

Tower Bridge in London [Shutterstock]

#UK­BIO19: Join GSK’s Hal Bar­ron and a group of top biotech ex­ecs for our 2nd an­nu­al biotech sum­mit in Lon­don

Over the past 10 years I’ve made a point of getting to know the Golden Triangle and the special role the UK biopharma industry plays there in drug development. The concentration of world class research institutes, some of the most accomplished scientists I’ve ever seen at work and a rising tide of global investment cash leaves an impression that there’s much, much more to come as biotech hubs are birthed and nurtured.

It’s fi­nal­ly over: Bio­gen, Ei­sai scrap big Alzheimer’s PhI­I­Is af­ter a pre­dictable BACE cat­a­stro­phe rais­es safe­ty fears

Months after analysts and investors called on Biogen and Eisai to scrap their BACE drug for Alzheimer’s and move on in the wake of a string of late-stage failures and rising safety fears, the partners have called it quits. And they said they were dropping the drug — elenbecestat — after the independent monitoring board raised concerns about…safety.

We don’t know exactly what researchers found in this latest catastrophe, but the companies noted in their release that investigators had determined that the drug was flunking the risk/benefit analysis.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 59,700+ biopharma pros reading Endpoints daily — and it's free.

Charles Nichols, LSU School of Medicine

Could psy­che­delics tack­le the obe­si­ty cri­sis? A long­time re­searcher in the field says his lat­est mouse study sug­gests po­ten­tial

Psychedelics have experienced a renaissance in recent years amid a torrent of preclinical and clinical research suggesting it might provide a path to treat mood disorders conventional remedies have only scraped at. Now a preclinical trial from a young biotech suggests at least one psychedelic compound has effects beyond the mind, and — if you believe the still very, very early hype — could provide the first single remedy for some of the main complications of obesity.

Ac­celeron drops a de­vel­op­ment pro­gram as #2 drug fails to spark func­tion­al ben­e­fits in pa­tients with a rare neu­ro­mus­cu­lar ail­ment

Acceleron is scrapping a muscular dystrophy development program underway for its number 2 drug in the pipeline after pouring over some failed mid-stage secondary data.

Gone is the ACE-083 project in patients with facioscapulohumeral muscular dystrophy. Their drug hit the primary endpoint on building muscle but flopped on key secondaries for functional improvements in patients, which execs felt was vital to the drug’s success.