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

Pi­o­neer­ing Click Chem­istry in Hu­mans

Reimagining cancer treatments

Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020, which is nearly one in six deaths. Recently, we have seen incredible advances in novel cancer therapies such as immune checkpoint inhibitors, cell therapies, and antibody-drug conjugates that have revamped cancer care and improved survival rates for patients.

Despite this significant progress in therapeutic targeting, why are we still seeing such a high mortality rate? The reason is that promising therapies are often limited by their therapeutic index, which is a measure of the effective dose of a drug, relative to its safety. If we could broaden the therapeutic indices of currently available medicines, it would revolutionize cancer treatments. We are still on the quest to find the ultimate cancer medicine – highly effective in several cancer types, safe, and precisely targeted to the tumor site.

Ivan Cheung, Eisai US chairman and CEO

Bio­gen, Ei­sai re­fresh amy­loid hy­poth­e­sis with PhI­II show­ing Alzheimer's med slows cog­ni­tive de­cline

In the first look at Phase III data for lecanemab, Eisai and Biogen’s follow-up Alzheimer’s drug to the embattled Aduhelm launch, results show the drug passed with flying colors on a test looking at memory, problem solving and other dementia metrics.

One of the most-watched Alzheimer’s therapies in the clinic, lecanemab met the study’s primary goal on the CDR-SB — Clinical Dementia Rating-Sum of Boxes — giving the biotech the confidence to ask for full approval in the US, EU and Japan by next March 31. The experimental drug reduced clinical decline on the scale by 27% compared to placebo at 18 months, the companies said Tuesday night Eastern time and Wednesday morning in Japan.

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Some­one old, some­one new: Mod­er­na pro­motes CTO, raids No­var­tis for re­place­ment amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Paul Hudson, Sanofi CEO (Photographer: Cyril Marcilhacy/Bloomberg via Getty Images)

Sanofi, Re­gen­eron’s Dupix­ent scores an­oth­er in­di­ca­tion with first-ever ap­proval for nodu­lar skin dis­or­der

Sanofi chief executive Paul Hudson told investors earlier this year that the Big Pharma was going to emphasize its sales kingpin Dupixent moving forward.

He wasn’t joking — the megablockbuster drug and sales king, recording just shy of $2 billion in sales this past quarter, has now officially secured its fifth indication from the FDA.

Sanofi and Regeneron, who jointly work on Dupixent development and commercialization, announced the new development on Thursday, saying that the FDA gave the all-clear to Dupixent to treat patients with prurigo nodularis, a rare autoimmune disorder characterized by a persistent, severe itch — and also visualized by hard, extremely itchy bumps known as nodules that form on the skin. The FDA noted in its announcement that it is the agency’s first approval for the disease.

Nooman Haque, head of life sciences and healthcare at Silicon Valley Bank, and John Carroll

I’m head­ed to Lon­don soon for #EU­BIO22. Care to join me?

It was great getting back to a live ESMO conference/webinar in Paris followed by a live pop-up event for the Endpoints 11 in Boston. We’re staying on the road in October with our return for a live/streaming EUBIO22 in London.

Silicon Valley Bank’s Nooman Haque and I are once again jumping back into the thick of it with a slate of virtual and live events on October 12. I’ll get the ball rolling with a virtual fireside chat with Novo Nordisk R&D chief Marcus Schindler, covering their pipeline plans and BD work.

Vlad Coric, Biohaven CEO (Photo Credit: Andrew Venditti)

As Amy­lyx de­ci­sion waits in the wings, Bio­haven’s ALS drug sinks (again) in plat­form tri­al

The FDA’s decision on Amylyx’s ALS drug is set to come out sometime Thursday. In a space with few drugs, any approval would be a major landmark.

But elsewhere in the ALS field, things are a bit more tepid.

Thursday morning, Biohaven announced that its drug verdiperstat failed its arm of an ALS platform trial led by Massachusetts General Hospital. According to a press release, the drug did not meet its primary endpoint — improvement on an ALS functional status test — or any key secondary endpoints at 24 weeks. The trial had enrolled 167 patients, giving them either verdiperstat or placebo twice a day.

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Sens. Rand Paul (R-KY) and Cory Booker (D-NJ) (Olivier Douliery/Sipa USA (Sipa via AP Images))

Sen­ate pass­es bill to re­work an­i­mal test­ing re­quire­ments for drug de­vel­op­ers

The US Senate passed via unanimous consent on Thursday afternoon a bipartisan bill that would eliminate a federal mandate for animal testing for new drugs.

Touted as a much-needed modernization of FDA’s rules, co-sponsor Sens. Rand Paul (R-KY) and Cory Booker (D-NJ) have said the bill will stop lots of needless suffering of animals.

Pa­tient re­port finds con­sti­pa­tion con­di­tion not well man­aged, open­ing door for bet­ter ed­u­ca­tion from phar­ma

Advertising for constipation treatments often uses light-hearted humor in an effort to spur open discussions about the sometimes stigmatized topic. However, that may not be enough to get people to take the condition seriously, a new patient report from Phreesia finds.

Fewer than one-fifth (17%) of patients with constipation surveyed understand the longer-term health risks of constipation such as hemorrhoids and bowel incontinence. Many are trying to manage their condition with over-the-counter medicines, but often for much longer than recommended. An equal 68% say they use home remedies or OTC meds to manage constipation. But while 90% understand that OTCs are not intended for long-term use, 50% have used an OTC constipation medicine for more than a year.

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Cell and gene ther­a­pies from acad­e­mia: EMA to help 5 projects go­ing af­ter un­met clin­i­cal needs

The European Medicines Agency said Thursday that it’s launching a new pilot program to help academic and other nonprofit researchers developing advanced therapy medicinal products, which includes cell and gene therapies.

Academics have proven to be enormously useful in feeding new products, like chimeric antigen receptor (CAR)-T cell therapies first developed by Memorial Sloan Kettering, and ushered to the market by biopharma companies. Jean Bennett, formerly with the University of Pennsylvania, also saw her research lead to the approval of gene therapy Luxturna, which Roche now owns.