Al­ler­gan’s Botox miss­es the bulls­eye in PhII de­pres­sion study, but re­searchers con­fi­dent they can hit it in a ma­jor PhI­II

Mitchell Brin, Al­ler­gan

Al­ler­gan’s siz­able Phase II study test­ing Botox as a treat­ment for ma­jor de­pres­sion among women missed hit­ting sta­tis­ti­cal sig­nif­i­cance for the pri­ma­ry end­point at six weeks of ther­a­py. But it didn’t miss by much, and the low dose did score at a cou­ple of oth­er time points in the study, giv­ing Al­ler­gan $AGN ex­ecs enough con­fi­dence to move the ther­a­py in­to a ma­jor Phase III pro­gram.

Re­searchers put two dos­es of Botox — 30 units and 50 units — in­to the study, which re­cruit­ed 258 pa­tients. The 50-unit dose was a bust. But:

The treat­ment (LS mean for MADRS to­tal score com­pared to place­bo) dif­fer­ence for 30 U was -4.2 at 3 weeks (p- val­ue 0.005); -3.7 at week 6 (p-val­ue 0.053) and -3.6 at week 9 (p-val­ue 0.049).

“I think the im­por­tant thing in a Phase III en­vi­ron­ment is to in­crease the num­ber of pa­tients,” says Mitchell Brin, the CSO for Botox. You bring to bear a high­er sta­tis­ti­cal pow­er with less vari­abil­i­ty. And, he adds, “the da­ta are still very fresh.” They can learn more things about this treat­ment as they con­tin­ue to ex­plore the re­sults.

One oth­er big dif­fer­ence be­tween Phase II and Phase III, he adds, is that they will do away with the two dif­fer­ent site net­works used to test the 30 and 50 unit dos­es, which was re­quired to keep the study blind­ed. And Chief Com­mer­cial Of­fi­cer Bill Meury notes that if you con­sid­er the to­tal­i­ty of all the mid-stage da­ta now avail­able, it’s rea­son­able to be­lieve that Phase III — with more than one study need­ed for an ap­proval — can achieve sta­tis­ti­cal sig­nif­i­cance.

Ever­cor­eISI’s Umer Raf­fat wasn’t buy­ing it, though. His com­ment:

So wait: is that a re­al sig­nal or just noise for 30U?
–      We know there is no dose re­sponse
–      We know oth­er end­points like HAM-D are “nu­mer­i­cal­ly su­pe­ri­or” – i.e., not sta­tis­ti­cal­ly bet­ter
–      We know tri­al sites did not over­lap be­tween 30U and 50U dose … per­haps 30U just got bet­ter sites?
So why would AGN an­nounce that they are go­ing in­to Ph 3 on the heels of this da­ta?
My sense:  Botox has some off-la­bel sales in de­pres­sion any­ways … per­haps they don’t wan­na jinx that near-term … and let a ph 3 go on for years to come
Maybe I am be­ing too pes­simistic here … but the da­ta don’t read good on this one.

The da­ta un­der­score that the treat­ment is ac­tive against the dis­ease, in­sists Meury, “and if we can man­age for place­bo we have a good chance of hav­ing a suc­cess­ful tri­al.”

William Meury, Al­ler­gan

SS­RI drugs are plen­ti­ful and will prob­a­bly re­main front­line ther­a­pies dur­ing our life­times, says Meury.

“This will be an al­ter­na­tive for peo­ple who can’t tol­er­ate weight gain, sex­u­al dys­func­tion or oth­er ad­verse events,” he adds. But the ben­e­fit/risk ra­tio for Botox is very, very high, he adds. And the un­met med­ical need for this group of peo­ple re­mains high as well, mak­ing this the kind of prod­uct that can earn hun­dreds of mil­lions of dol­lars each year, “at base­line.”

Al­ler­gan CEO Brent Saun­ders has been one of the most pro­lif­ic deal­mak­ers in bio­phar­ma over the past year, af­ter its merg­er with Pfiz­er fell through. In this case, re­searchers were look­ing to see if they could nail down sol­id ev­i­dence of ex­pand­ing the use of its wrin­kle ther­a­py for de­pres­sion — which has proven to be one of the tough­est tar­gets in R&D.

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.

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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.

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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.

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