In blow to Shire, Roche bags an FDA OK for its block­buster he­mo­phil­ia A prospect

Guy Young, USC Keck School of Med­i­cine. Im­age: USC

De­spite be­ing dogged by ques­tions about safe­ty and an un­usu­al le­gal coun­ter­at­tack from ri­val Shire, Roche to­day scored an FDA ap­proval for emi­cizum­ab (ACE910), its he­mo­phil­ia A ther­a­py which will now hit the mar­ket as Hem­li­bra.

The drug is de­signed to bring to­geth­er fac­tor IXa and fac­tor X pro­teins to re­store the blood clot­ting process for he­mo­phil­ia A pa­tients, re­duc­ing the threat of bleeds. And an­a­lysts have pegged po­ten­tial sales at up to $5 bil­lion, though Reuters‘ most re­cent con­sen­sus was a con­sid­er­ably less frothy $1.6 bil­lion.

Sig­nif­i­cant­ly, the ap­proval comes more than three months ahead of its late-Feb­ru­ary PDU­FA date, reg­is­ter­ing as the 40th new mol­e­c­u­lar en­ti­ty of the year as the in­dus­try looks ready to cruise past the cur­rent-era record 44 new ap­provals achieved at CDER in 2015.

The ap­proval was based on some im­pres­sive da­ta on a drug that Roche has stead­fast­ly main­tained is a near cer­tain block­buster-to-be. But it al­so comes with a boxed warn­ing on a threat of blood clots and dam­age to blood ves­sels, which could al­so crimp sales.

Last sum­mer the phar­ma gi­ant laid out da­ta de­tail­ing how the drug re­duced the rate of treat­ed bleeds by 87%, hit­ting the pri­ma­ry end­point, the drug al­so hand­i­ly outscored by­pass­ing agents like Shire’s. Their ther­a­py slashed “on-de­mand BPAs across all bleed mea­sure­ments, in­clud­ing ze­ro treat­ed bleeds (62.9 per­cent vs. 5.6 per­cent), ze­ro treat­ed spon­ta­neous bleeds (68.6 per­cent vs. 11.1 per­cent), ze­ro treat­ed joint bleeds (85.7 per­cent vs. 50.0 per­cent), ze­ro treat­ed tar­get joint bleeds (94.3 per­cent vs. 50.0 per­cent) and ze­ro bleeds over­all, which in­cludes all treat­ed and non-treat­ed bleeds (37.1 per­cent vs. 5.6 per­cent).”

Along the way, Roche blamed Shire’s by­pass­ing agents for throm­boem­bol­ic events that they saw in their study, ad­vis­ing doc­tors to stop us­ing FEI­BA.

Shire, to put it mild­ly, flipped.

“To im­ply a cause-and-ef­fect of FEI­BA hav­ing caused the se­vere ad­verse events is mis­lead­ing,” Shire hema­tol­ogy chief Ju­liana Dierks told Reuters. “We are look­ing for­ward to trans­paren­cy. Give us the da­ta, give us the facts.”

Shire al­so claimed that Roche has been mis­lead­ing­ly of­fer­ing a look at “treat­ed bleeds” — a sec­ondary end­point — in­stead of the “num­ber of bleeds over time,” orig­i­nal­ly laid out as the pri­ma­ry end­point in HAVEN 1. And by blam­ing throm­boem­bol­ic in­ci­dents in the study — with one pa­tient dy­ing of a rec­tal he­m­or­rhage — on its by­pass­ing agent, Shire al­so main­tained that it had been dam­aged. Shire sought an in­junc­tion against Roche in Ger­many, but the ac­tion was re­ject­ed by the court and the com­plaint hasn’t slowed its Big Phar­ma ri­val at all.

How bad could this get for Shire? Bern­stein an­a­lysts say Hem­li­bra along with new ther­a­pies from No­vo Nordisk and Bay­er could shrink its share of the he­mo­phil­ia mar­ket from 49% to 29%

Roche has nev­er done any­thing but shrug the as­sault off. The phar­ma gi­ant is los­ing patent pro­tec­tion on three fran­chise drugs, and it needs to field ma­jor new drugs to fill the gap.

Hem­li­bra is priced to do just that. Roche, like a grow­ing num­ber of com­pa­nies, is us­ing an av­er­age whole­sale price based on av­er­age weight. At an av­er­age weight of about 127 pounds, Roche says, the cost “is ap­prox­i­mate­ly $482,000 for the first year of treat­ment and then ap­prox­i­mate­ly $448,000 per year, which is less than half of the WAC of the on­ly oth­er ap­proved pro­phy­lac­tic treat­ment for these pa­tients.”

The price fits in at the low­er rung of the list of the 10 most ex­pen­sive drugs in the world, all among the rare dis­ease crowd.

“To­day’s ap­proval pro­vides a new pre­ven­ta­tive treat­ment that has been shown to sig­nif­i­cant­ly re­duce the num­ber of bleed­ing episodes in pa­tients with he­mo­phil­ia A with Fac­tor VI­II in­hibitors,” said Richard Paz­dur, whose ti­tles in­clude act­ing di­rec­tor of the Of­fice of Hema­tol­ogy and On­col­o­gy Prod­ucts. “In ad­di­tion, pa­tients treat­ed with Hem­li­bra re­port­ed an im­prove­ment in their phys­i­cal func­tion­ing.”

“Peo­ple with he­mo­phil­ia A who de­vel­op in­hibitors face sig­nif­i­cant chal­lenges pre­vent­ing bleeds and typ­i­cal­ly re­quire in­fu­sions of med­i­cine mul­ti­ple times a week, which can be es­pe­cial­ly dif­fi­cult for young chil­dren and their fam­i­lies,” said Guy Young, di­rec­tor of he­mo­sta­sis and throm­bo­sis pro­gram, Chil­dren’s Hos­pi­tal Los An­ge­les, and pro­fes­sor of pe­di­atrics, Uni­ver­si­ty of South­ern Cal­i­for­nia Keck School of Med­i­cine. “This new med­i­cine has been shown to re­duce the fre­quen­cy of bleeds com­pared to the cur­rent­ly avail­able med­i­cines and on­ly needs to be in­ject­ed once a week. This could make a mean­ing­ful dif­fer­ence for these chil­dren.”

Im­age: Roche, John Mc­Carter

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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UP­DAT­ED: CMS to re­strict cov­er­age of Bio­gen's con­tro­ver­sial Alzheimer's drug to on­ly clin­i­cal tri­als

The Centers for Medicare and Medicaid Services on Tuesday said it will only pay for Biogen’s Aduhelm and other FDA-approved anti-amyloid monoclonal antibodies for Alzheimer’s disease under CMS-approved randomized controlled trials.

The draft national coverage decision, which insurers nationwide are likely to follow, makes clear that CMS will be looking for randomized controlled trials that “demonstrate a clinically meaningful benefit in cognition and function.” That will be a tough task for Biogen, which previously showed conflicting benefits from past Aduhelm trials that were initially cut short due to futility and then resurrected for the accelerated approval.

CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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