FDA tells Sprout Phar­ma, like it or not the black box on Ad­dyi stays, but we will di­lute the warn­ing

When the con­tro­ver­sial first drug for low sex­u­al de­sire in women was fi­nal­ly grant­ed ap­proval in 2015, crit­ics ac­cused the FDA of bow­ing to pres­sure from ad­vo­cates by sanc­tion­ing the use of a drug that was found to be mar­gin­al­ly ef­fec­tive in clin­i­cal tri­als, and dan­ger­ous when tak­en with al­co­hol. On Thurs­day, the agency re­buked the mak­er of the drug, Ad­dyi, by re­fus­ing to en­ter­tain the com­pa­ny’s quest to dis­card the black box warn­ing car­ried by the treat­ment, but agreed to damp­en the strong warn­ing on the ba­sis of post­mar­ket­ing da­ta.

Ad­dyi, known chem­i­cal­ly as flibanserin, is de­signed for pre­menopausal women whose lack of sex­u­al de­sire caus­es dis­tress. Pa­tients who took Ad­dyi in a clin­i­cal tri­al had an in­crease of about one sex­u­al­ly sat­is­fy­ing event per month, ver­sus those giv­en a place­bo.

The pink pill — nick­named the “fe­male Vi­a­gra” — has lit­tle in com­mon with the Pfiz­er $PFE block­buster, which was ap­proved decades ago as the pi­o­neer­ing erec­tile dys­func­tion treat­ment. While Vi­a­gra im­pacts blood flow and is tak­en as-need­ed, Ad­dyi was de­signed to ac­ti­vate sex­u­al im­puls­es in the brain and must be tak­en every day.

In par­tic­u­lar, Ad­dyi’s la­bel car­ries a black box warn­ing, high­light­ing the risk of po­ten­tial­ly dan­ger­ous low blood pres­sure and faint­ing, no­tably when tak­en with al­co­hol.

On Thurs­day, the reg­u­la­tor made clear that Ad­dyi’s la­bel must be mod­i­fied to clar­i­fy there is still a con­cern about con­sum­ing al­co­hol close in time to tak­ing Ad­dyi, but that it does not have to be avoid­ed com­plete­ly. Af­ter an­a­lyz­ing da­ta from post­mar­ket­ing stud­ies, the FDA said the warn­ing in­side the black box should re­flect that women should dis­con­tin­ue drink­ing al­co­hol at least two hours be­fore tak­ing Ad­dyi at bed­time or to skip the dose that evening and that women should not con­sume al­co­hol at least un­til the morn­ing af­ter tak­ing Ad­dyi at bed­time.

The reg­u­la­tor has prover­bial­ly put its foot down and is com­pelling Ad­dyi mak­er Sprout Phar­ma­ceu­ti­cals to make the change af­ter the two par­ties were un­able to reach an agree­ment. “We work dili­gent­ly with com­pa­nies to make la­bel­ing up­dates but oc­ca­sion­al­ly are un­able to reach an agree­ment. In those rare cas­es…we have im­por­tant au­thor­i­ties to com­pel com­pa­nies to make safe­ty la­bel­ing changes that are crit­i­cal for the safe use of an ap­proved prod­uct,” the agency said in a state­ment.

Cindy Eck­ert and Robert White­head

Click on the im­age to see the full-sized ver­sion

The founders of Sprout Phar­ma­ceu­ti­cals have long had a strained re­la­tion­ship with the FDA. Chief Cindy White­head (now Cindy Eck­ert) co-found­ed the com­pa­ny with her then-hus­band Robert White­head in 2011, af­ter sell­ing an­oth­er drug com­pa­ny they had spawned to­geth­er af­ter it was is­sued mul­ti­ple FDA warn­ings re­lat­ed to its mar­ket­ing tac­tics.

Sprout pur­chased flibanserin from Ger­many’s Boehringer In­gel­heim, which orig­i­nal­ly de­vel­oped it and took it to the FDA, on­ly to be de­nied ap­proval in 2010. Un­der Sprout, the drug was eval­u­at­ed in ad­di­tion­al stud­ies, but the FDA re­ject­ed it again in 2013. In­censed by the re­jec­tion, Sprout — with the sup­port of some women’s groups —  ag­gres­sive­ly lob­bied the FDA to get the drug across the fin­ish line, by ac­cus­ing the US agency of gen­der bias (a charge the reg­u­la­tor de­nied).

The FDA fi­nal­ly ap­proved the treat­ment — with a boxed warn­ing — on Au­gust 19, 2015, the very next day Sprout an­nounced it was be­ing sold to Valeant (now Bausch Health) for a tidy $1 bil­lion. The hon­ey­moon didn’t last long — in 2017, an em­bat­tled Valeant re­turned Sprout to its orig­i­nal own­ers.

Last month, Sprout is­sued a cheer­ful press re­lease, sug­gest­ing post­mar­ket­ing da­ta in­di­cat­ed that treat­ment with Ad­dyi did not re­sult in faint­ing or hy­poten­sion that re­quired med­ical at­ten­tion. But the FDA took is­sue with that as­sess­ment, say­ing the safe­ty pre­cau­tions built in­to the tri­al did not al­low for an ad­e­quate as­sess­ment of this risk. “For ex­am­ple, women with low blood pres­sure while ly­ing down…were not per­mit­ted to stand up to have blood pres­sure mea­sure­ments tak­en or had to have re­peat­ed blood pres­sure mea­sure­ments while ly­ing down un­til they were high enough for the women to safe­ly stand up. As a re­sult, the da­ta col­lect­ed had miss­ing or de­layed blood pres­sure mea­sure­ments from these women while stand­ing.”

The reg­u­la­tor was al­so not sat­is­fied with how the post­mar­ket­ing tri­als were con­duct­ed, point­ing out that in one tri­al, there were “miss­ing or de­layed mea­sure­ments for blood pres­sure from when the women were first lay­ing down to when they stood up that are crit­i­cal in de­ter­min­ing the risk of hy­poten­sion and syn­cope when tak­ing Ad­dyi and al­co­hol to­geth­er.” The agency al­so flagged that many more women had miss­ing or de­layed blood pres­sure mea­sure­ments when they took Ad­dyi and al­co­hol to­geth­er, com­pared to when they con­sumed al­co­hol or Ad­dyi alone.

Al­to­geth­er, the “pat­tern of the miss­ing or de­layed mea­sure­ments” pro­vides fur­ther ev­i­dence of an in­ter­ac­tion be­tween Ad­dyi and al­co­hol that can en­hance the risk of hy­poten­sion and faint­ing, the agency un­der­scored.

Sprout must com­ply with the FDA’s la­bel­ing de­ci­sion or risk mon­e­tary fines and/or en­force­ment in the form of prod­uct seizure and in­junc­tion. The com­pa­ny has un­til April 16 to ap­peal.

End­points News has con­tact­ed Sprout for com­ment.

Im­age source: Allen G. Breed AP

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,500+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,500+ biopharma pros reading Endpoints daily — and it's free.

SQZ, Ery­tech kick off $57M cell ther­a­py part­ner­ship; Jean-Paul Kress lands new CEO gig at Mor­phoSys

→ In a mar­riage of two tech­nolo­gies meant to make cell ther­a­pies more pow­er­ful, SQZ Biotech is team­ing up with France’s Ery­tech Phar­ma for a col­lab­o­ra­tion, with $57 mil­lion re­served for the first project and $50 mil­lion for each sub­se­quent ap­proval (prod­uct or in­di­ca­tion). Hav­ing ac­cess to Ery­tech’s method of fash­ion­ing ther­a­peu­tics from red blood cells, the Cam­bridge, MA-based com­pa­ny said, will am­pli­fy SQZ’s cell en­gi­neer­ing ca­pa­bil­i­ties and al­low them to de­vleop a new class of im­munomod­u­la­to­ry ther­a­pies. Its own tech — so far ap­plied in can­cer but al­so has po­ten­tial in di­a­betes — tem­po­rary dis­rupts the cell mem­brane by squeez­ing the cell, thus cre­at­ing a brief win­dow for tar­get ma­te­ri­als such as anti­gens to en­ter.

UP­DAT­ED: In sur­prise switch, Bris­tol-My­ers is sell­ing off block­buster Ote­zla, promis­ing to com­plete Cel­gene ac­qui­si­tion — just lat­er

Apart from revealing its checkpoint inhibitor Opdivo blew a big liver cancer study on Monday, Bristol-Myers Squibb said its plans to swallow Celgene will require the sale of blockbuster psoriasis treatment Otezla to keep the Federal Trade Commission (FTC) at bay.

The announcement — which has potentially delayed the completion of the takeover to early 2020 — irked investors, triggering the New York-based drugmaker’s shares to tumble Monday morning in premarket trading.

Celgene’s Otezla, approved in 2014 for psoriasis and psoriatic arthritis, is a rising star. It generated global sales of $1.6 billion last year, up from the nearly $1.3 billion in 2017. Apart from the partial overlap of Bristol-Myers injectable Orencia, the company’s rival oral TYK2 psoriasis drug is in late-stage development, after the firm posted encouraging mid-stage data on the drug, BMS-986165, last fall. With Monday’s decision, it appears Bristol-Myers is favoring its experimental drug, and discounting Otezla’s future.

The move blindsided some analysts. Credit Suisse’s Vamil Divan noted just days ago:

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,500+ biopharma pros reading Endpoints daily — and it's free.

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.

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.

Tasly Bio­phar­ma pitch­es long-await­ed IPO — will it trig­ger an­oth­er $1B gold rush on HKEX?

In the run up to the Hong Kong stock ex­change’s an­tic­i­pat­ed rule change — open­ing the door for Chi­nese pre-rev­enue biotechs to go pub­lic clos­er to home — more than a year ago, Tasly Bio­phar­ma was one of the big play­ers whose ru­mored in­ter­est helped stoke en­thu­si­asm for the new list­ing venue. The com­pa­ny has since kept the drum­roll rum­bling in the back­ground, rais­ing a pre-IPO round and con­vinc­ing part­ner Trans­gene to swap own­er­ship in a joint ven­ture for eq­ui­ty. Now the oth­er shoe has fi­nal­ly dropped as ex­ecs out­line plans for a pipeline dom­i­nat­ed by car­dio­vas­cu­lar drugs.

With 4 more biotech IPOs due to wrap up Q2, how is the class of 2019 far­ing?

With 22 biotech IPOs on the books and four more set to price in the last week of June, in­vest­ment ad­vis­er Re­nais­sance Cap­i­tal has tak­en the pulse of the re­cent rush.

By the IPO ex­perts’ count, 25 out of 32 health­care of­fer­ings this year have been from biotechs — dif­fer­ing slight­ly from Brad Lon­car’s tal­ly — and the over­all pic­ture is one of un­der­per­for­mance. While they av­er­aged a first-day re­turn of 9.0%, col­lec­tive­ly they have trad­ed down to a 5.9% re­turn. Turn­ing Point $TP­TX and Cor­texyme $CRTX emerged on top at the half-year mark, ris­ing 135% and 109% re­spec­tive­ly.

Eye­ing a $500M peak sales pot, Almi­rall dou­bles down on le­brik­izum­ab as Der­mi­ra lines up PhI­II

With eyes on what it be­lieves is a $500 mil­lion peak rev­enue op­por­tu­ni­ty in Eu­rope, Barcelona-based Almi­rall has stepped up with $50 mil­lion in cash to take up the op­tion on Der­mi­ra’s IL-13 an­ti-in­flam­ma­to­ry drug le­brik­izum­ab just ahead of the start of Phase III. And there’s an­oth­er $30 mil­lion due as the late-stage pro­gram gets geared up.

That shouldn’t be long from now, as Der­mi­ra ex­pects to be­gin the late-stage tri­al work for atopic der­mati­tis be­fore the end of this year as it fol­lows a trail that ex­ecs in­sist leads to block­buster re­turns. Along the way, they’ll need to take on the 600-pound go­ril­la in atopic der­mati­tis: the IL-13/IL-4 drug Dupix­ent, from Re­gen­eron and Sanofi. Ri­vals al­so in­clude Leo Phar­ma, in its piv­otal with tralok­izum­ab, and Anap­tys­Bio in the hunt with a mid-stage pro­gram for etokimab, pre­vi­ous­ly re­ferred to as ANB020.