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)

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Gossamer Bio CEO Faheem Hasnain at Endpoints' #BIO22 panel (J.T. MacMillan Photography for Endpoints News)

Gos­samer’s Fa­heem Has­nain de­fends a round of pos­i­tive PAH da­ta as a clear win. But can these PhII re­sults stand up to scruti­ny?

Gossamer Bio $GOSS posted a statistically significant improvement for its primary endpoint in the key Phase II TORREY trial for lead drug seralutinib on Tuesday morning. But CEO Faheem Hasnain has some explaining to do on the important secondary of the crucial six-minute walk distance test — which will be the primary endpoint in Phase III — as the data on both endpoints fell short of expectations, missing one analyst’s bar on even modest success.

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Kristen Hege, Bristol Myers Squibb SVP, early clinical development, oncology/hematology and cell therapy (Illustration: Assistant Editor Kathy Wong for Endpoints News)

Q&A: Bris­tol My­er­s' Kris­ten Hege on cell ther­a­py, can­cer pa­tients and men­tor­ing the next gen­er­a­tion

Kristen Hege leads Bristol Myers Squibb’s early oncology discovery program carrying on from the same work at Celgene, which was acquired by BMS in 2019. She’s known for her early work in CAR-T, having pioneered the first CAR-T cell trial for solid tumors more than 25 years ago.

However, the eminent physician-scientist is more than just a drug developer mastermind. She’s also a practicing physician, mother to two young women, an avid backpacker and intersecting all those interests — a champion of young women and people of color in STEM and life sciences.

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US sup­ports ex­ten­sion for Covid-19 IP waiv­er de­ci­sion

After much debate, the US government is now calling for a deadline extension to discuss a controversial potential IP waiver for Covid-19 diagnostics and therapeutics.

Over the last five months, the Office of the United States Trade Representative said it has consulted with members of Congress, public health advocates, organized labor groups, academics, think tanks, companies and trade associations on the WTO’s recent TRIPS agreement, which established a 5-year waiver of certain patent requirements on Covid-19 vaccines.

Mar­ket­ingRx roundup: Phar­mas lay off Twit­ter ads for an­oth­er week; WPP un­cov­ers LGBTQ+ mar­ket­ing find­ings

When Twitter’s new owner Elon Musk tweeted this weekend, “Just a note to thank advertisers for returning to Twitter,” he likely wasn’t talking about big pharma companies. The vast majority of the top spending pharma advertisers had not returned last week, according to updated tracking data Pathmatic for Endpoints News.

Only three pharma advertisers spent any money at all, which is about the same as the past several weeks. AstraZeneca rejoined the active advertiser list, although at $700 spent hardly worth a personal Musk expression of gratitude. GSK remained active with $3,500 spent ad much lower than its previous spending, according to the Pathmatics data. Only Bayer spent any significant amount in advertising, with $244,000 spent last week, but that’s a considerable drop from almost $500,000 spent on OTC, prescription and corporate Twitter ads in each of the previous two weeks.

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Rick Modi, Affinia Therapeutics CEO

Ver­tex-part­nered gene ther­a­py biotech Affinia scraps IPO plans

Affinia Therapeutics has ditched its plans to go public in a relatively closed-door market that has not favored Nasdaq debuts for the drug development industry most of this year. A pandemic surge in 2020 and 2021 opened the doors for many preclinical startups, which caught Affinia’s attention and gave the gene therapy biotech confidence in the beginning days of 2022 to send in its S-1.

But on Friday, Affinia threw in the S-1 towel and concluded now is not the time to step onto Wall Street. The biotech has put out few public announcements since the spring of this year. Endpoints News picked the startup as one of its 11 biotechs to watch last year.

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Bob Duggan, Summit Therapeutics co-CEO

Bounc­ing from ma­jor set­back, Sum­mit hands out $500M cash for can­cer drug — thanks to a loan from bil­lion­aire CEO

After hitting a dead end with Summit Therapeutics’ lead program, Bob Duggan has found the drug that he believes will usher into a compelling second act. So compelling, in fact, that it involves $500 million cash — and he’s taking money out of his own pocket to fund the deal.

Striking a partnership with Akeso Therapeutics out of China, Summit is bringing in a bispecific antibody that blocks both PD-1 and VEGF called ivonescimab. Akeso, which has a PD-1/CTLA-4 bispecific approved in China, has already taken ivonescimab into multiple clinical trials, including a Phase III in lung cancer.

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Gilmore O’Neill, Editas Medicine CEO

Ed­i­tas re­ports ear­ly-stage da­ta from two pa­tients in sick­le cell dis­ease

One company is moving forward in its bid to make a cell therapy for sickle cell disease viable — and after previous setbacks, including a hold earlier this year, execs are touting some really early data.

Editas Medicine announced Tuesday morning that it had positive safety and efficacy data from two patients in a Phase I/II trial investigating EDIT-301, a cell therapy candidate that Editas developed. Safety was measured in both patients, and efficacy data are from only the first patient dosed.

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Jonathan Montagu, HotSpot Therapeutics CEO

Ab­b­Vie puts up $40M to li­cense a treat­ment from HotSpot Ther­a­peu­tics

HotSpot Therapeutics has managed to gain some steam financially in the past few years, as the company wrangled several multi-million dollar raises. But its latest deal not only puts more cash into its pockets, it also connects with a major name in pharma.

On Tuesday, AbbVie and HotSpot announced they have entered an “exclusive” global collaboration, with the option to license HotSpot’s IRF5 program, which is designed to treat autoimmune diseases. The deal will see AbbVie hand HotSpot $40 million upfront, with the biotech eligible to receive $295 million in “option fees” and R&D milestones.