Reata rout leaves next project in doubt

Bardoxolone looks dead after yesterday’s adcom vote, but what about omaveloxolone?

Reata Pharmaceuticals looks like it has reached the end of the road with its lead project, bardoxolone, after a damning FDA advisory committee meeting yesterday. The panel raised serious questions about the way the company had presented its interactions with the FDA to investors.

With Reata’s credibility unwinding, investors could now cast a critical eye over the group’s second asset, omaveloxolone, which is set for submission in the first quarter of next year in Friedreich’s ataxia. Notably, Reata has changed its stance about carrying out a second pivotal study of this project, something that could ring alarm bells.

13-0

Reata is seeking approval for bardoxolone in chronic kidney disease caused by Alport syndrome, for which there are no approved therapies. The project has a Pdufa date of 25 February, 2022, but a complete response letter now looks likely following the adcom, which came down 13-0 against bardoxolone.

The filing was supported by the Cardinal trial; this met its primary and secondary endpoints, which evaluated on and off-treatment effects on estimated glomerular filtration rate (eGFR), a surrogate outcome (Reata’s worsened Cardinal results could still be good enough, November 12, 2019).

But FDA briefing documents spelled out concerns about the design of Cardinal; the agency said it had raised these concerns during the course of bardoxolone’s development.

This appears to be at odds with the picture painted by Reata. During the group’s first-quarter results call its chief R&D officer, Colin Myer, said: “We've been transparent with our discussions with the agency dating back to our pre-IND meeting [in] Alport syndrome…They gave us the design for the Alport syndrome trial, which we've executed.”

This apparent disconnect led to usually supportive sellside analysts from Leerink concluding today: “The bardoxolone saga highlights the pitfalls of relying on a management team's characterisation of what the FDA has said they will require for the approval of a drug.”

More shots

Bardoxolone is still in development in autosomal dominant polycystic kidney disease – in the recently upsized phase 3 Falcon trial – and in rapidly progressing chronic kidney disease, in the phase 2 Merlin study. But hopes here cannot now be high, especially given similarities between these studies and Cardinal.

Reata has lost its big prize: bardoxolone was forecast to bring in sales of over $2bn by 2026, according to sellside consensus compiled by Evaluate Pharma.

It still has a chance to salvage something with omaveloxolone, but this project’s prospects are far from clear. Last year, the FDA concluded that the existing data were not enough to support approval, and another pivotal study looked like the only way forward (FDA sends Reata back to the drawing board, November 25, 2020).

As late as May, Reata was planning to start a second pivotal trial this year. However, the group changed its tune after a pre-NDA meeting – which it said the FDA had asked it to request – and is now gearing up for a filing in early 2022 without carrying out another study.  

What does all this mean for omaveloxolone’s chances? It is hard to say without any direct comments from the FDA, which does not disclose details of its meetings with companies.

But, as Leerink put it: “It is difficult to have much confidence in the regulatory outlook for omaveloxolone since there is even less information about what the FDA will require for approval, and we must rely on the company's rendition.”

Reata’s stock plunged 43% this morning; this came on top of a 38% drop on Monday, when the briefing documents came out. But the group is still worth $1.1bn. If omaveloxolone goes the way of bardoxolone Reata could have further to fall still.

Share This Article