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

Paul Hudson, Sanofi CEO (Getty Images)

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