Vivek Ra­maswamy’s Urovant claims a big win in PhI­II — but ques­tions linger about a cheap gener­ic and their brand­ed ri­val

Af­ter the great Ax­o­vant im­plo­sion that swept away its high­ly tout­ed Alzheimer’s drug, Roivant chief Vivek Ra­maswamy need­ed one of the biotechs in his fast-grow­ing league of drug de­vel­op­ers to win a big Phase III tri­al. Based on to­day’s top-line re­lease for Urovant’s Phase III uri­nary in­con­ti­nence drug vibegron, the team is claim­ing that vic­to­ry and prep­ping an ap­pli­ca­tion for the FDA.

But there are some lin­ger­ing ques­tions about the cheap gener­ic that was used as an ac­tive com­para­tor in the study, and it’s dri­ving the biotech’s stock in­to the red Tues­day morn­ing.

Urovant’s drug hit sta­tis­ti­cal sig­nif­i­cance for both co-pri­ma­ry end­points and all 7 sec­on­daries when com­pared against a place­bo. But the drug was al­so test­ed along­side an old gener­ic drug called toltero­dine. And there the re­search showed that vibegron “achieved nu­mer­i­cal­ly bet­ter ef­fi­ca­cy that toltero­dine.”

In the slide show pre­sen­ta­tion this morn­ing, the com­pa­ny went on to il­lus­trate the specifics of the com­para­tor arms ver­sus place­bo, but re­searchers did not run a p val­ue for the Urovant drug against the gener­ic. But they were rel­a­tive­ly close, as you can see here:

Source: Urovant

Urovant’s drug cut in­stances of in­con­ti­nence by 2 from a base­line of 3.43, achiev­ing a clear win over the 1.4 drop in the place­bo arm. Toltero­dine, though, came much clos­er at 1.8. Both drugs beat the place­bo with sta­tis­ti­cal sig­nif­i­cance.

For uri­na­tion fre­quen­cy, there was a sim­i­lar spread. The place­bo arm hit a drop of 1.3, with a neg­a­tive 1.8 for vibegron and -1.6 for toltero­dine. Vibegron hit sta­tis­ti­cal dif­fer­ence ver­sus place­bo, toltero­dine did not. But there was no di­rect com­par­i­son of the ex­per­i­men­tal drug and the cheap place­bo.

In their an­nounce­ment back in 2012, Astel­las post­ed these re­spons­es for Myr­be­triq.

Myr­be­triq 25 mg, in­con­ti­nence episodes were re­duced by 1.36 episodes from a base­line of 2.65, a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion of 0.40 vs. place­bo in 12 weeks. The num­ber of uri­na­tions was re­duced by 1.65 uri­na­tions from a base­line of 11.68, a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion of 0.47 vs. place­bo in 12 weeks.

Myr­be­triq 50 mg, in­con­ti­nence episodes were re­duced by 1.49 episodes from a base­line of 2.71, a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion of 0.40 vs. place­bo in 12 weeks.  Num­ber of uri­na­tions was re­duced by 1.75 uri­na­tions from a base­line of 11.70, a sta­tis­ti­cal­ly sig­nif­i­cant re­duc­tion of 0.55 vs. place­bo in 12 weeks.

You can be sure that an­a­lysts will al­so be fill­ing in the blanks by ex­trap­o­lat­ing the head-to-head com­par­isons them­selves.

Urovant’s pitch is built around demon­strat­ing a bet­ter safe­ty and ef­fi­ca­cy pro­file than the an­ti­cholin­er­gics — like toltero­dine, where there’s been a link with de­men­tia — and the block­buster drug Myr­be­triq (mirabegron), which was launched by Astel­las back in 2012. Vibegron is a be­ta-3 drug, like Myr­be­triq, which is backed by patents that ex­pire in 2023 — about 3 years af­ter Urovant could ex­pect an ap­proval.

Giv­en that this drug is in­tend­ed for a mass mar­ket with mil­lions of pa­tients, teas­ing out the specifics of how a new, brand­ed drug com­pares to well es­tab­lished mar­ket­ed drugs would be cru­cial to its longterm suc­cess or fail­ure on the mar­ket. 

Biren Amin

Urovant, which has a mar­ket cap of $442 mil­lion, is let­ting it all ride on this Phase III. Ra­maswamy nabbed the drug from Mer­ck with a small, $25 mil­lion up­front — one of a slate of deals he struck ear­ly on as he grabbed ther­a­pies that had been side­lined at the ma­jors and aimed them for quick cat­a­lysts.

Big gam­ble? Jef­feries’ Biren Amin not­ed that a clear win here would be worth a 100% spike in the stock, with a neg­a­tive out­come elim­i­nat­ing up to half of its mar­ket cap.

That’s not what hap­pened, though. Af­ter pop­ping up 20% be­fore the bell, the stock turned south, plung­ing to a mi­nus 17% as in­vestors tried to sort out the re­sults for them­selves.


Im­age: Vivek Ra­maswamy at the US-Chi­na Bio­phar­ma In­no­va­tion & In­vest­ment Sum­mit, 2018. PHARM­CUBE, END­POINTS

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