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.

Brent Saunders [Getty Photos]

UP­DAT­ED: Ab­b­Vie seals $63B deal to buy a trou­bled Al­ler­gan — spelling out $1B in R&D cuts

Brent Saunders has found his way out of the current fix he’s in at Allergan $AGN. He’s selling the company to AbbVie for $63 billion in the latest example of the hot M&A market in biopharma.

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Two biotech uni­corns swell pro­posed IPOs, eye­ing a $600M-plus wind­fall

We’ve been wait­ing for the ar­rival of Bridge­Bio’s IPO to top off the wave of new biotech of­fer­ings sweep­ing through Nas­daq at the end of H1. And now we learn that it’s been sub­stan­tial­ly up­sized.

Ini­tial­ly pen­ciled in at a uni­corn-sized $225 mil­lion, the KKR-backed biotech has spiked that to the neigh­bor­hood of $300 mil­lion, look­ing to sell 20 mil­lion shares at $14 to $16 each. That’s an added 5 mil­lion shares, re­ports Re­nais­sance Cap­i­tal, which fig­ures the pro­posed mar­ket val­u­a­tion for Neil Ku­mar’s com­pa­ny at $1.8 bil­lion.

No­var­tis holds back the copy­cat brigade's at­tack on its top drug fran­chise — for now

A fed­er­al judge has put a gener­ic chal­lenge to No­var­tis’ block­buster mul­ti­ple scle­ro­sis drug Gilenya on hold while a patent fight plays out in court.

Judge Leonard P. Stark is­sued a tem­po­rary in­junc­tion ear­li­er this week, forc­ing My­lan, Dr. Red­dy’s Lab­o­ra­to­ries and Au­robindo Phar­ma to shelve their launch plans to al­low the patent fight to pro­ceed. He ruled that al­low­ing the gener­ics in­to the mar­ket now would per­ma­nent­ly slash the price for No­var­tis, even if it pre­vails. 

Af­ter rais­ing $158M, this up­start's founders have star back­ers and plans to break new ground in gene ther­a­py

Back in 2014, Stephanie Tagliatela opted to take an early exit out of her PhD program after working in Mark Bear’s lab at MIT, where she specialized in the synaptic connections between neuronal cells in the brain. She never finished that PhD, but she and fellow MIT student Kartik Ramamoorthi — who was on the founding team at Voyager — came away with some ideas for a gene therapy startup.

Today, fully 5 years later, she and Ramamoorthi are taking the wraps off of a $104 million mega-round designed to take the cumulative work of their preclinical formative stage for Encoded Therapeutics into human studies. They’ve now raised $158 million since starting out in Illumina’s incubator in the Bay Area, and they believe they are firmly on track to do something unique in gene therapy.

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Novotech CEO Dr. John Moller

Novotech CRO Award­ed Frost & Sul­li­van Best Biotech CRO Asia-Pa­cif­ic 2019

Known in the in­dus­try as the Asia-Pa­cif­ic CRO, Novotech is now lead CRO ser­vices provider for the grow­ing num­ber of in­ter­na­tion­al biotechs se­lect­ing the re­gion for their stud­ies.

Re­flect­ing this Asia-Pa­cif­ic growth, Novotech staff num­bers are up 20% since De­cem­ber 2018 to 600 in-house clin­i­cal re­search peo­ple across a full range of ser­vices, across the re­gion.

Novotech’s ca­pa­bil­i­ties have been rec­og­nized by an­a­lysts like Frost & Sul­li­van, most re­cent­ly with the pres­ti­gious Asia-Pa­cif­ic CRO Biotech of the year award for best prac­tices in clin­i­cal re­search for biotechs for the fifth year. See oth­er awards here.

Sanofi/Re­gen­eron mus­cle ahead of a ri­val No­var­tis/Roche team, win first ap­proval in key rhi­nos­i­nusi­tis field

Re­gen­eron and their part­ners at Sanofi have beat the No­var­tis/Roche team to the punch on an­oth­er key in­di­ca­tion for their block­buster an­ti-in­flam­ma­to­ry drug Dupix­ent. The drug team scored an ac­cel­er­at­ed FDA ap­proval for chron­ic rhi­nos­i­nusi­tis with nasal polyps, mak­ing this the first such NDA for the field.

An­a­lysts have been watch­ing this race for awhile now, as Sanofi/Re­gen­eron won a snap pri­or­i­ty re­view for what is now their third dis­ease in­di­ca­tion for this treat­ment. And they’re not near­ly done, build­ing up hopes for a ma­jor fran­chise.

FDA re­jects Ac­er's rare dis­ease drug, asks for new tri­al — shares crater

Ac­er Ther­a­peu­tics’ bid to re­pur­pose celipro­lol — a be­ta-block­er on the mar­ket for hy­per­ten­sion — as a treat­ment for a rare, in­her­it­ed con­nec­tive tis­sue dis­or­der has hit a se­vere set­back. The New­ton, Mass­a­chu­setts-based com­pa­ny on Tues­day said the FDA re­ject­ed the drug and has asked for an­oth­er clin­i­cal tri­al.

The com­pa­ny’s shares $AC­ER cratered near­ly 77% to $4.47 in Tues­day morn­ing trad­ing.

Richard Gonzalez testifying in front of Senate Finance Committee, February 2019 [AP Images]

Ab­b­Vie's $63B buy­out spot­lights the re­turn of ma­jor M&A deals — de­spite the back­lash

Big time M&A is back. But for how long?

Over the past 18 months we’ve now seen three major buyouts announced: Takeda/Shire; Bristol-Myers/Celgene and now AbbVie/Allergan. And with this latest deal it’s increasingly clear that the sharp fall from grace suffered by high-profile players which have seen their share prices blasted has created an opening for the growth players in big pharma to up their game — in sharp contrast to the popular bolt-on deals that have been driving the growth strategy at Novartis, Merck, Roche and others.

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Top an­a­lyst finds a sil­ver lin­ing in Ab­b­Vie’s $63B Al­ler­gan buy­out — but there’s a catch

Af­ter get­ting beat up on all sides from mar­ket ob­servers who don’t much care for the lat­est mega-deal to ar­rive in bio­phar­ma, at least one promi­nent an­a­lyst now is start­ing to like what he sees in the num­bers for Ab­b­Vie/Al­ler­gan.

But it’s go­ing to take some en­cour­age­ment if Ab­b­Vie ex­ecs want it to last.

Ab­b­Vie’s mar­ket cap de­clined $20 bil­lion on Tues­day as the stock took a 17% hit dur­ing the day. And SVB Leerink’s Ge­of­frey Porges can see a dis­tinct out­line of an up­side af­ter re­view­ing the fun­da­men­tals of the deal.

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