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.

Jeff Al­bers

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)

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

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.

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.

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.