Sec­ond time's a charm for os­teo­poro­sis drug from Am­gen, UCB as FDA pan­el grants its bless­ing

Looks like Am­gen and UCB’s os­teo­poro­sis drug is head­ed to the fin­ish line, af­ter an FDA pan­el large­ly sup­port­ed its ap­proval on Wednes­day. But if ap­proved, it will like­ly car­ry a black box warn­ing ad­vis­ing against its use in pa­tients with high car­dio­vas­cu­lar risk.

The rec­om­men­da­tion fol­lows a rosy re­view from FDA staff post­ed on Mon­day, who un­der­scored ro­mosozum­ab’s ef­fi­ca­cy in post­menopausal women with a high risk of frac­ture had been es­tab­lished, and sug­gest­ed that the CV sig­nal ob­served in some tri­als may not be a sig­nif­i­cant wor­ry. An in­de­pen­dent pan­el of ex­perts whose rec­om­men­da­tions the FDA typ­i­cal­ly fol­lows en­dorsed the drug, in light of its ef­fi­ca­cy in pa­tients that usu­al­ly have few treat­ment op­tions, but sug­gest­ed the CV risk be char­ac­ter­ized post ap­proval.

Over­all, pan­el mem­bers vot­ed 18-1 in fa­vor of ap­proval. The sin­gle “no” vote came from a pa­tient rep­re­sen­ta­tive, who thought the drug was ef­fi­ca­cious but want­ed CV risk to be de­ter­mined pri­or to ap­proval.

Ro­mosozum­ab — which is to be sold un­der the brand name Eveni­ty — func­tions pre­dom­i­nant­ly as a bone an­a­bol­ic agent that stim­u­lates bone growth. Pan­el dis­cus­sions sug­gest­ed the drug, which is al­ready ap­proved in Japan and is un­der re­view in Eu­rope, will need to fea­ture a black box warn­ing de­scrib­ing the in­crease in CV events ob­served, and the com­pa­ny will like­ly have to con­duct a post-mar­ket­ing study to char­ac­ter­ize the car­dio risk of the drug in the Unit­ed States. Pa­tients with high os­teo­porot­ic risk tend to be old­er, and hence may al­so be at high­er risk for car­dio events, var­i­ous pan­elists ac­knowl­edged.

Michael Yee

“In our view, the pan­el gen­er­al­ly thought the in­creased CV event rate was like­ly to be spu­ri­ous and still vot­ed for ap­proval; our base case is FDA ap­proval in H1:19 with a black­box that sug­gests use most­ly in pa­tients with high-risk os­teo­poro­sis who have not had a MI/stroke with­in the past 12 months,” Jef­feries’ Michael Yee wrote in a note, adding that Lil­ly’s os­teo­poro­sis drug For­teo car­ries a black box warn­ing high­light­ing the risk of can­cer and still rakes in about $2 bil­lion.

In the US, one in two women over the age of 50 will ex­pe­ri­ence an os­teo­porot­ic frac­ture — an in­ci­dence that sur­pass­es that of heart at­tack, stroke and breast can­cer com­bined, ac­cord­ing to the Na­tion­al Os­teo­poro­sis Foun­da­tion, which es­ti­mates os­teo­poro­sis will be re­spon­si­ble for three mil­lion frac­tures re­sult­ing in $25.3 bil­lion in costs by 2025.

“Even when lim­it­ing use (of the drug) more broad­ly be­cause of the­o­ret­i­cal CV risk,” ro­mosozum­ab rep­re­sents a more than $500 mil­lion world­wide op­por­tu­ni­ty, Yee said.

Ro­mosozum­ab was test­ed in three late-stage stud­ies: the 7,180-pa­tient place­bo-con­trolled FRAME study in post­menopausal women with os­teo­poro­sis,; the 4,093-pa­tient ARCH study in post­menopausal women in os­teo­poro­sis, which test­ed the drug against an os­teo­poro­sis drug orig­i­nal­ly made by Mer­ck called al­en­dronate; and the 245-pa­tient place­bo-con­trolled BRIDGE study in men with os­teo­poro­sis.

All three piv­otal stud­ies showed the mon­o­clon­al an­ti­body was ef­fec­tive, but se­ri­ous CV ad­verse events were ob­served the ARCH and BRIDGE tri­al, which prompt­ed the FDA to is­sue a com­plete re­sponse let­ter to de­ny the ap­proval of ro­mosozum­ab in post­menopausal women with os­teo­poro­sis. Tak­ing in­to ac­count the CV sig­nal and feed­back from the FDA about the pauci­ty of an­a­bol­ic agents, the duo re-sub­mit­ted an ap­pli­ca­tion to mar­ket drug last year, but for a nar­row­er pa­tient pop­u­la­tion: post­menopausal women with os­teo­poro­sis who car­ry a high risk of frac­ture, or pa­tients who have failed or are in­tol­er­ant to ex­ist­ing os­teo­poro­sis ther­a­pies.

Am­gen $AMGN and UCB co-de­vel­oped the drug and, if ap­proved, will split the prof­its.

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