Aca­dia says Nu­plazid cleared main goal in de­pres­sion study, but da­ta ap­pear mixed

In a news-heavy week for de­pres­sion drugs, with of­fer­ings from Alk­er­mes $ALKS and Sage $SAGE un­der FDA scruti­ny, Aca­dia Phar­ma­ceu­ti­cals $ACAD on Wednes­day said “weight­ed av­er­age re­sults” sug­gest pi­ma­vanserin (Nu­plazid) met the main goal in a mid-stage study in­volv­ing pa­tients with ma­jor de­pres­sive dis­or­der (MDD) — but a con­tro­ver­sial two-stage tri­al de­sign in­di­cat­ed the drug failed to im­press in the sec­ond tranche of the tri­al, de­spite the p-val­ue that emerged from the pooled da­ta.

Al­though ini­tial en­thu­si­asm pushed the stock up in pre-mar­ket trad­ing, it was in the red once the mar­ket opened on Wednes­day morn­ing.

Tri­als test­ing drugs for psy­chi­atric dis­or­ders are sus­cep­ti­ble to a large place­bo ef­fect and typ­i­cal­ly fail. In an ef­fort to avoid this, Aca­dia’s CLAR­I­TY tri­al test­ed pi­ma­vanserin us­ing the same se­quen­tial par­al­lel com­par­i­son de­sign (SPCD) as Alk­er­mes’ de­pres­sion drug ALKS 5461, which was al­so the sub­ject of much con­fu­sion in a staff re­view post­ed by the reg­u­la­tor on Tues­day — the de­sign brought up a host of un­re­solved sta­tis­ti­cal ques­tions re­gard­ing the most ap­pro­pri­ate method of analy­sis in SPCD.

The SPCD de­sign in­volves two stages:

  • In the first stage, pa­tients ei­ther get the drug or a place­bo, but more pa­tients are ran­dom­ized to get the place­bo
  • In the sec­ond stage, non-re­spon­ders from the place­bo group are re-ran­dom­ized to get the drug or the place­bo

Re­sults from the two stages are then pooled to pro­vide a sin­gle over­all test of hy­poth­e­sis. The tri­al test­ed pi­ma­vanserin against a place­bo in 207 adult MDD pa­tients who had not ad­e­quate­ly re­spond­ed to ex­ist­ing first-line ther­a­py.

In the first stage, pa­tients on pi­ma­vanserin (n=52) demon­strat­ed a sig­nif­i­cant im­prove­ment in HAMD-17 (p=0.0003) ver­sus place­bo (n=155).

But sig­nif­i­cant­ly, in the sec­ond stage, pa­tients on pi­ma­vanserin (n=29) did not show a sig­nif­i­cant sep­a­ra­tion from place­bo (n=29), prompt­ing crit­ics to sug­gest the tri­al was a fail­ure dressed in sheep’s cloth­ing.

Aca­dia con­clud­ed that in the “weight­ed merged analy­sis” of the two stages, the drug just met the main goal (p=0.039) of in­duc­ing a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion in de­pres­sive symp­toms on the Hamil­ton de­pres­sion rat­ing scale (HAMD-17) com­pared to place­bo. Dis­con­tin­u­a­tions due to ad­verse events were 1.2% for pi­ma­vanserin and 3.2% for place­bo, and one pa­tient in the pi­ma­vanserin group and the place­bo arm re­port­ed se­ri­ous ad­verse events, but these SAEs were deemed not to be re­lat­ed to the drug and both sub­jects com­plet­ed the study, Aca­dia said.

Pi­ma­vanserin be­longs to a class of drugs called se­lec­tive sero­tonin in­verse ag­o­nists (SSIA), which tar­gets the 5-HT2A re­cep­tor that is be­lieved to play a crit­i­cal role in de­pres­sion, psy­chosis, and oth­er neu­ropsy­chi­atric dis­or­ders.

The con­tro­ver­sial drug, which is al­ready sold un­der the brand name Nu­plazid for Parkin­son’s dis­ease psy­chosis, gained no­to­ri­ety af­ter a se­ries of re­ports sug­gest­ed its mak­er had mis­rep­re­sent­ed the dan­gers of us­ing the drug and had em­ployed ques­tion­able tac­tics to mar­ket it, prompt­ing an FDA re­view that lat­er reaf­firmed the drug’s safe­ty pro­file.

Aca­dia aims to test the drug for MDD in a Phase III tri­al in the first half of 2019, and — to the sur­prise of an­a­lysts in a post-an­nounce­ment con­fer­ence call — sug­gest­ed the CLAR­I­TY tri­al would serve as one of two piv­otal tri­als re­quired to sub­mit a sup­ple­men­tal mar­ket­ing ap­pli­ca­tion for an MDD ap­proval.

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.

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.

President Donald Trump (left) and Moncef Slaoui, head of Operation Warp Speed (Alex Brandon, AP Images)

UP­DAT­ED: White House names fi­nal­ists for Op­er­a­tion Warp Speed — with 5 ex­pect­ed names and one no­table omis­sion

A month after word first broke of the Trump Administration’s plan to rapidly accelerate the development and production of a Covid-19 vaccine, the White House has selected the five vaccine candidates they consider most likely to succeed, The New York Times reported.

Most of the names in the plan, known as Operation Warp Speed, will come as little surprise to those who have watched the last four months of vaccine developments: Moderna, which was the first vaccine to reach humans and is now the furthest along of any US effort; J&J, which has not gone into trials but received around $500 million in funding from BARDA earlier this year; the joint AstraZeneca-Oxford venture which was granted $1.2 billion from BARDA two weeks ago; Pfizer, which has been working with the mRNA biotech BioNTech; and Merck, which just entered the race and expects to put their two vaccine candidates into humans later this year.

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 83,100+ biopharma pros reading Endpoints daily — and it's free.