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.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.

Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Emer Cooke, EMA director (AP Photo/Geert Vanden Wijngaert)

Ahead of FDA, EMA rec­om­mends au­tho­riz­ing new gene ther­a­py treat­ment for ul­tra-rare dis­ease

Aromatic amino acid decarboxylase (AADC) deficiency is an ultra-rare genetic disease that leaves patients unable to produce certain hormones in the brain, such as dopamine and serotonin, usually leading to developmental delays, weak muscle tone and inability to control the movement of the limbs. It can also lead to multiple organ failure.

To date, there have been no treatments approved for AADC deficiency, which has been identified in less than 150 patients.

Ather­sys tries to post-hoc-an­a­lyze its way out of an­oth­er tri­al fail for stroke stem cell ther­a­py

Athersys’ stem cell therapy has failed yet again.

In a 206-person trial conducted in Japan, Athersys’ stem cell therapy for stroke failed its primary endpoint of “excellent outcome,” a combined measure of three stroke recovery scores.

While a greater percentage of patients in the treatment group reached the primary endpoint compared to placebo, that difference was not statistically significant.

Siddhartha Mukherjee (Brian Ach/Getty Images for The New Yorker)

All Blue's $733M bid to ac­quire Zymeworks turns hos­tile as board bat­tles back — af­ter a biotech celebri­ty jumps in

Yesterday, the team at All Blue Capital — bent on the takeover of a badly battered Zymeworks — brought in celebrated oncologist, Pulitzer prize-winning writer and biotech exec Siddhartha Mukherjee to add some glitz to their proposed board. But they’re still not winning over any converts.

This morning, Zymeworks’ board officially turned this acquisition offer into a hostile showdown, rejecting the unsolicited offer and marshaling its forces to prevent a buyout at $10.50 per share.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 142,600+ biopharma pros reading Endpoints daily — and it's free.