Dai­ichi Sankyo 'dis­ap­point­ed' as FDA ex­perts spurn AML drug but vote in fa­vor of rare tu­mor drug

Dai­ichi Sankyo has of­fered up the fresh­est case study of just where the line is drawn on can­cer drugs show­ing in­cre­men­tal — or even ques­tion­able — ben­e­fits, as crit­i­cal in­ter­nal re­views from the FDA trans­lat­ed in­to dif­fer­ing ad­vi­so­ry com­mit­tee opin­ions on two of its pitch­es.

By a 3-8 mar­gin, the on­col­o­gy ex­perts con­vened by the agency shot down the Japan­ese drug­mak­er’s case for its acute myeloid leukemia drug quizar­tinib, hav­ing vot­ed in fa­vor of pex­i­dar­tinib in the morn­ing ses­sion. Pex­i­dar­tinib treats be­nign tu­mors known as symp­to­matic tenosyn­ovial gi­ant cell tu­mor.

De­signed specif­i­cal­ly for FLT3-ITD–pos­i­tive AML, quizar­tinib was her­ald­ed as a sig­nif­i­cant new op­tion for re­frac­to­ry pa­tients who are count­ing their last days. Dai­ichi Sankyo bagged the ty­ro­sine ki­nase in­hibitor in a buy­out of Am­bit Bio­sciences val­ued at $410 mil­lion in 2014. Last Au­gust, the com­pa­ny scored a break­through ther­a­py des­ig­na­tion for it on the back of piv­otal da­ta that showed a 27% over­all sur­vival rate com­pared to 20% in the chemother­a­py arm.

Richard Paz­dur

But ad­comm mem­bers sided with FDA re­view­ers in wor­ry­ing that the re­sults, de­spite be­ing sta­tis­ti­cal­ly sig­nif­i­cant, had to do with im­bal­ances be­tween the drug and chemo co­horts. Com­pared to the chemo arm, the quizar­tinib group had a high­er per­cent­age of pa­tients who went on to re­ceive hematopoi­et­ic stem cell trans­plants, a low­er num­ber of non-treat­ed cas­es, and few­er in­stances of in­com­plete OS da­ta — all point­ing to­ward a po­ten­tial bias.

Richard Paz­dur, the pow­er­ful di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, chimed in at the meet­ing, say­ing he hasn’t come across a re­sult like this in 20 years.

“While we are dis­ap­point­ed by the out­come of to­day’s ODAC vote, we will work close­ly with the FDA as it com­pletes the re­view of our sub­mis­sion,” said An­toine Yver, Dai­ichi Sankyo’s glob­al head of on­col­o­gy R&D.

An­toine Yver

Reg­u­la­tors, who are not oblig­ed to fol­low the ad­comm’s ad­vice but of­ten do, will have un­til Au­gust 25 to de­cide af­ter ex­tend­ing an ear­li­er dead­line to re­view more da­ta. Dai­ichi Sankyo’s loss here could be Astel­las’ and No­var­tis’ gain as they con­tin­ue to carve out a place for Xospa­ta and Ry­dapt, re­spec­tive­ly.

It’s a sharp con­trast with pex­i­dar­tinib, which would be the first non-sur­gi­cal treat­ment for a rare but of­ten de­bil­i­tat­ing con­di­tion in­volv­ing tu­mors in joints and ten­dons.

Here the main con­cern was liv­er tox­i­c­i­ty, a con­cern that had pre­vi­ous­ly cur­tailed en­roll­ment in a Phase III. While ad­comm mem­bers ac­knowl­edged the safe­ty is­sues, the ma­jor­i­ty of them trust­ed a de­cent risk eval­u­a­tion and mit­i­ga­tion strat­e­gy, or REMS, would suf­fi­cient­ly low­er the risks.

Though the FDA al­so raised ques­tions about ef­fi­ca­cy, cit­ing a “high lev­el of miss­ing da­ta at Week 25,” 12 of the ex­perts on the pan­el had no prob­lem en­dors­ing the ben­e­fits over the risks.

“I did not see the lon­gi­tude in the da­ta around 25 weeks and this is why I took more of the con­ser­v­a­tive side,” added one of the 3 who vot­ed no. “I was wor­ried about the ef­fi­ca­cy and qual­i­ty of life da­ta be­yond 25 weeks.”

The PDU­FA date for pex­i­dar­tinib is Au­gust 3.

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.

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 83,200+ 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.

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.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 83,200+ biopharma pros reading Endpoints daily — and it's free.

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 83,200+ 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.