Af­ter a PhI­II fail­ure, the FDA de­liv­ers Blue­print an ex­pect­ed CRL

Some CRLs come as lit­tle sur­prise.

This morn­ing, the FDA re­ject­ed Blue­print Med­i­cines’ ap­pli­ca­tion to have their can­cer drug Ay­vak­it (avapri­tinib) ap­proved for fourth-line gas­troin­testi­nal stro­mal tu­mors, or GIST. Al­ready, though, in late April, the drug had failed the ma­jor test for that in­di­ca­tion: A Phase III tri­al pit­ting Ay­vak­it against the al­ready-ap­proved Bay­er GIST drug, re­go­rafenib.

Pa­tients on re­go­rafenib did bet­ter than those on Ay­vak­it. Af­ter the tri­al, Blue­print said they were end­ing the pro­gram for 3rd and 4th line GIST pa­tients. An­a­lysts dis­count­ed the in­di­ca­tion from their pro­jec­tions.

“Blue­print will pro­vide the VOY­AGER da­ta to the FDA as part of the on­go­ing re­view of avapri­tinib in 4L GIST (PDU­FA May 14), though ex­pects that an ap­proval is un­like­ly,” Cowen’s Marc Frahm wrote in a note to in­vestors.

To­day’s an­nounce­ment was set up by a split de­ci­sion the FDA made in Jan­u­ary. Al­though Blue­print was fac­ing a Feb­ru­ary PDU­FA, the agency chose to ad­dress the two in­di­ca­tions ad­dressed in Blue­print’s NDA sep­a­rate­ly, han­dling one ear­ly and boot­ing the oth­er down the road.

For GIST pa­tients with a rare mu­ta­tion with PDGFRa, the FDA saw clear ben­e­fit for the drug, with Ay­vak­it show­ing an 84% re­sponse rate. But in gen­er­al fourth-line GIST, the agency want­ed more da­ta. They de­layed the dead­line to May 14, by which time the Phase III tri­al would have re­sults.

With the Phase III fail­ure al­ready out, the of­fi­cial CRL changes the fore­cast lit­tle for Blue­print, but even when the study re­sults emerged, an­a­lysts urged against pan­ic. “GIST was not the the­sis,” Frahm wrote, not­ing that Blue­print was mov­ing ahead in RET-pos­i­tive can­cers and a rare dis­ease called sys­temic mas­to­cy­to­sis, where in­vestors saw greater po­ten­tial.

In the AS­CO ab­stract dump ear­li­er this week, Blue­print re­vealed da­ta from their RET-tar­get­ed can­cer drug pralse­tinib, show­ing a few com­plete re­spons­es and al­most match­ing Eli Lil­ly’s re­cent­ly ap­proved Retev­mo on over­all re­sponse — set­ting up a po­ten­tial dual mar­ket for years.

The best promise for GIST pa­tients with­out the PDFRa mu­ta­tion now lies with De­ci­phera, which has been go­ing to head to head with Blue­print on the in­di­ca­tion for a year. The com­pa­ny’s drug, ripretinib, has earned a break­through des­ig­na­tion and a pri­or­i­ty re­view for fourth-line GIST, set­ting up a de­ci­sion in Au­gust. The drug is de­signed to tar­get not on­ly PDGFRa but the KIT mu­ta­tions that fu­el a ma­jor­i­ty of GIST tu­mors.

In a late-stage study of 129 pa­tients, the drug pro­duced a pro­gres­sion-free sur­vival of 6.6 months com­pared to 1 month in place­bo, al­though the re­sponse rate was on­ly 9.4%. A study com­par­ing its ef­fects in sec­ond-line pa­tients to the ef­fects of Pfiz­er’s Su­tent is on­go­ing.

So­cial: Shut­ter­stock

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

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.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

Endpoints Premium

Premium subscription required

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

Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.

Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

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.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

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.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

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.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

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.

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,100+ biopharma pros reading Endpoints daily — and it's free.