Short the launch starts early for Urovant 

For Urovant, beating placebo in a pivotal trial of vibegron was the easy part. 

For vibegron to have any chance of becoming a big commercial success Urovant needs to prove that it is unquestionably a better option than existing treatments for overactive bladder. Topline results released today are encouraging, but the company still has a very hard task ahead of it. 

True, vibegron does not seem to carry the same hypertension risk as Astellas's Myrbetriq; both are β3-adrenergic receptor agonists, and this important safety issue could well turn out to be Urovant’s most important marketing message. But, beyond this, the company could find it difficult to argue for meaningful points of differentiation when it finds itself in front of those holding the purse strings. 

Ahead of more detailed data firm conclusions are hard to draw, but at the very least Urovant has confirmed that it has a safe and active product. Vibegron convincingly beat placebo in the Empowur study and, though a previous trial run by Merck & Co made this a likely outcome, Urovant now looks to have a good chance of winning approval.  

Cracking the market was always going to be the tough part. First-line antimuscarinics are available generically, and Myrbetriq, which is expected to sell $864m in the US this year despite its hypertension warning, will probably lose exclusivity in 2023 (First big test approaches for Urovant, March 12, 2019).

Utility in patients with high blood pressure will open up vibegron to new patients wanting to try a β3-adrenergic receptor agonist, but Urovant will want more than this niche. The company today pointed to faster onset of action and lack of drug-drug interactions as important attributes, but divergences on key efficacy measures are harder to see. 

Data from the β3-adrenergic receptor agonist class
Myrbetriq: placebo-adjusted results from phase III trials (all @ wk 12)
  Study 1 Study 2 Study 3
  50mg 50mg 25mg 50mg
Avg daily micturations −0.60 −0.61 −0.47 −0.42
Avg daily incontinence episodes −0.41 −0.34 −0.40 −0.42
Note: All met statistical significance. Source: US drug label.
Vibegron: placebo-adjusted results from Merck and Urovant studies 
  Merck phIIb (wk 8) Empowur (wk 12)   
  50mg 100mg 75mg  
Avg daily micturations −0.64 −0.91 −0.50  
Avg daily incontinence episodes −0.72 −0.71 −0.60  
Note: All met statistical significance. Source: European Urology, company presentation.

Notably, the 75mg dose being pursued by Urovant did not perform as strongly as dosages tested in the earlier Merck study, the caveats of cross-trial comparison notwithstanding. Urovant measured its primary endpoints at 12 weeks, against 8 weeks for Merck, which could offer an explanation.

Ahead of the data Urovant executives told investors that replicating the Merck results would be “an upside case” that could make vibegron a blockbuster. Investors’ response today suggests that this has not materialised. Shares in the company, which floated at $14 last September, fell 18% to $11.45 in early trade.

The Empowur trial also included an active arm, the antimuscarinic tolterodine, and vibegron proved itself “directionally better” than this drug on most measures; a comparison of the two drugs was not part of the statistical analysis. Again, this is encouraging, particularly as the β3-adrenergic receptor agonists are also generally more tolerable than this older drug class. 

Overall, however, the results serve to emphasise just how carefully Urovant will have to tread when it comes to pricing. Dissatisfaction with existing treatments for overactive bladder certainly creates an opportunity. But Urovant will be a small company launching alone, something that always strikes fear into the hearts of investors. 

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