Blue­print stum­bles in PhI­II GIST tri­al, send­ing stock slid­ing, but an­a­lysts preach cau­tion

When the FDA ap­proved Blue­print’s first drug three months ago, they split their de­ci­sion. Ay­vak­it would be ap­proved for gas­troin­testi­nal stro­mal tu­mors (GIST) with a rare mu­ta­tion called PDGFRa. The oth­er half of their ap­pli­ca­tion for plain old fourth line GIST would have to wait. Reg­u­la­tors want­ed to know how the drug per­formed in a Phase III tri­al.

Re­sults are now in from that Phase III tri­al and they spelled a death-knell. In a study of 476 pa­tients with third or fourth line GIST, Ay­vak­it (avapri­tinib) per­formed worse on the pri­ma­ry end­point than the al­ready-ap­proved Bay­er GIST drug, re­go­rafenib. Pro­gres­sion-free sur­vival was 4.2 months, com­pared with 5.6 months for Ay­vak­it.

Blue­print’s drug did have a high­er re­sponse rate — 17% com­pared with 7% — but that ap­peared as lit­tle con­so­la­tion. The com­pa­ny is dis­con­tin­u­ing de­vel­op­ment of the drug for those pa­tients.

“We will con­tin­ue to ad­vance our pipeline with clear near-term pri­or­i­ties in sys­temic mas­to­cy­to­sis and RET-al­tered can­cers,” CEO Jeff Al­bers said in a state­ment.

The com­pa­ny’s stock $BPMC took a sig­nif­i­cant hit, falling 20% from $70.90 to $56.71, ef­fec­tive­ly eras­ing over $800 mil­lion in val­ue.

Cowen’s Marc Frahm sug­gest­ed, though, that this was an over­re­ac­tion, writ­ing in a note to in­vestors that “GIST was not the the­sis.” The drug could still be po­ten­tial­ly used off-la­bel in fourth line GIST, Frahm wrote, but they were still re­mov­ing 3rd and 4th line GIST from their fu­ture sales pro­jec­tions. Nev­er­the­less, he ar­gued the tri­al said lit­tle about Ay­vak­it’s po­ten­tial in sys­temic mas­to­cy­to­sis — a rare dis­ease where mast cells ac­cu­mu­late in or­gans — or, in com­bi­na­tion with an­oth­er ex­per­i­men­tal drug, in can­cers with RET mu­ta­tions.

“We have re­moved sales for the broad 3/4L GIST in­di­ca­tions but con­tin­ue to view BPMC shares as un­der­val­ued,” Frahm wrote, pric­ing them at $83.

An­drew Berens at SVB Leerink was less up­beat but echoed the call for cau­tion. The fail­ure will “fun­da­men­tal­ly hit” Blue­print, he said, but the greater po­ten­tial lay else­where.

“Over­all, we be­lieve that GIST is less im­por­tant to the BPMC the­sis and think that in­vestors are like­ly to step in af­ter this read­out for more long-term op­por­tu­ni­ties in RET-dri­ven ma­lig­nan­cies and sys­temic mas­to­cy­to­sis (SM) with up­com­ing cat­a­lyst,” Berens wrote.

Blue­print had been in a two-per­son race with De­ci­phera to get a drug ap­proved for GIST — a rare form of sar­co­ma in the di­ges­tive sys­tem — dri­ven by a mu­ta­tion to the platelet-de­rived growth al­pha gene, or PDGFRa. Ay­vak­it was ap­proved un­der ac­cel­er­at­ed ap­proval, while De­ci­phera awaits an Au­gust de­ci­sion date from the FDA. Both com­pa­nies are al­so pur­su­ing sys­temic mas­to­cy­to­sis and 2nd line GIST.

De­ci­phera does not have a tri­al for 3rd line GIST, but Berens said the com­pa­ny could ben­e­fit if on­col­o­gists de­cide to try their drug off-la­bel in that set­ting.

So­cial im­age: Jeff Al­bers, Blue­print CEO (CN­BC)

Tar­get­ing a Po­ten­tial Vul­ner­a­bil­i­ty of Cer­tain Can­cers with DNA Dam­age Re­sponse

Every individual’s DNA is unique, and because of this, every patient responds differently to disease and treatment. It is astonishing how four tiny building blocks of our DNA – A, T, C, G – dictate our health, disease, and how we age.

The tricky thing about DNA is that it is constantly exposed to damage by sources such as ultraviolet light, certain chemicals, toxins, and even natural biochemical processes inside our cells.¹ If ignored, DNA damage will accumulate in replicating cells, giving rise to mutations that can lead to premature aging, cancer, and other diseases.

Roivant par­lays a $450M chunk of eq­ui­ty in biotech buy­out, grab­bing a com­pu­ta­tion­al group to dri­ve dis­cov­ery work

New Roivant CEO Matt Gline has crafted an all-equity upfront deal to buy out a Boston-based biotech that has been toiling for several years now at building a supercomputing-based computational platform to design new drugs. And he’s adding it to the Erector set of science operations that are being built up to support their network of biotech subsidiaries with an eye to growing the pipeline in a play to create a new kind of pharma company.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

The fu­ture of mR­NA, J&J's vac­cine ad­comm, Mer­ck­'s $1.85B au­toim­mune bet and more

Welcome to the third installment of 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.

If this report was helpful in recapping it all for you, please do share it with your colleagues.

Get ready for FDA’s third Covid-19 vaccine

On the heels of a ringing endorsement from FDA reviewers earlier in the week, J&J‘s single-dose vaccine — which proved 66% effective at preventing symptomatic Covid-19, and 85% effective at stopping severe disease 28 days after administration — the advisory committee convened by the agency voted unanimously to recommend its emergency use authorization. It was “a relatively easy call,” according to one of the committee members — although that doesn’t mean they didn’t have questions. Jason Mast has the highlights from the discussion, including new information from the company, on this live blog.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.

Fol­low biotechs go­ing pub­lic with the End­points News IPO Track­er

The Endpoints News team is continuing to track IPO filings for 2021, and we’ve designed a new tracker page for the effort.

Check it out here: Biopharma IPOs 2021 from Endpoints News

You’ll be able to find all the biotechs that have filed and priced so far this year, sortable by quarter and listed by newest first. As of the time of publishing on Feb. 25, there have already been 16 biotechs debuting on Nasdaq so far this year, with an additional four having filed their S-1 paperwork.

Steve Cutler, Icon CEO (Icon)

In the biggest CRO takeover in years, Icon doles out $12B for PRA Health Sci­ences to fo­cus on de­cen­tral­ized clin­i­cal work

Contract research M&A had a healthy run in recent years before recently petering out. But with the market ripe for a big buyout and the Covid-19 pandemic emphasizing the importance of decentralized trials, Wednesday saw a tectonic shift in the CRO world.

Icon, the Dublin-based CRO, will acquire PRA Health Sciences for $12 billion in a move that will shake up the highest rungs of a fragmented market. The merger would combine the 5th- and 6th-largest CROs by 2020 revenue, according to Icon, and the merger will set the newco up to be the second-largest global CRO behind only IQVIA.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.

Roche and Genen­tech re­searchers plot $53M dis­cov­ery quest aimed at spark­ing a 'Holy moly' piv­ot in neu­ro R&D

Roche and Genentech have committed $53 million to back a 10-year quest aimed at going back to the drawing board to use new technology and fresh scientific insights to generate a pipeline of drugs for neurological diseases.

Researchers from both Roche and its big South San Francisco hub — mixing teams from gRED and pRED this time — will mix it up with the scientists drawn together for the Weill Neurohub — formed in 2019 as a joint research partnership involving UCSF, Berkeley and the University of Washington — in an exploration of the field to develop new therapies for some of the toughest diseases in drug R&D: Alzheimer’s, Parkinson’s, Huntington’s, ALS and autism.

Am­gen, As­traZeneca speed to­ward fil­ing next-gen an­ti­body for asth­ma af­ter un­cork­ing full late-stage da­ta

On the hunt for a novel competitor to Sanofi and Regeneron’s Dupixent in severe asthma, Amgen and AstraZeneca posted “exciting” results from their next-gen antibody late last year. Now, the partners are showing their hands, and the results look good enough for approval.

Amgen and AstraZeneca’s tezepelumab plus standard of care cut the rate of severe asthma attacks by 56% at the one-year mark compared with SOC alone, according to full data from the Phase III NAVIGATOR study presented Friday at the virtual American Academy of Allergy, Asthma & Immunology meeting. And those significant results were consistent regardless of patients’ baseline eosinophil counts.

With dust set­tled on ac­tivist at­tack, Lau­rence Coop­er leaves Zio­pharm to a new board

Laurence Cooper has done his part.

In the five years since he left a tenured position at Houston’s MD Anderson Cancer Center to become CEO of Boston-based Ziopharm, he’s steered the small-cap immunotherapy player through patient deaths in trials, clinical holds, short attacks and, most recently, an activist attack on the board.

So when the company has “fantastic news” like an IND clearance for a TCR T cell therapy program, he’s ready to pass on the baton.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.

Doug Ingram (file photo)

Why not? Sarep­ta’s third Duchenne MD drug sails to ac­cel­er­at­ed ap­proval

Sarepta may be running into some trouble with its next-gen gene therapy approach to Duchenne muscular dystrophy. But when it comes to antisense oligonucleotides, the well-trodden regulatory path is still leading straight to an accelerated approval for casimersen, now christened Amondys 45.

We just have to wait until 2024 to find out if it works.

Amondys 45’s approval was unceremonious, compared to its two older siblings. There was no controversy within the FDA over approving a drug based on a biomarker rather than clinical benefit, setting up a powerful precedent that still haunts acting FDA commissioner Janet Woodcock as biotech insiders weighed her potential permanent appointment; no drama like the FDA issuing a stunning rejection only to reverse its decision and hand out an OK four months later, which got more complicated after the scathing complete response letter was published; no anxious tea leaf reading or heated arguments from drug developers and patient advocates who were tired of having corticosteroids as their loved ones’ only (sometimes expensive) option.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 102,100+ biopharma pros reading Endpoints daily — and it's free.