GI toxicity hits midstage Sanofi GLP-1 drug as patients drop out

Sanofi said gastrointestinal concerns have made its experimental GLP-1 phase 2 drug SAR425899 “not acceptable for clinical use,” but it is undertaking new tests to try to get around dosing issues, which it blames for the AEs.

In its release this morning, the French Big Pharma announced: “The phase 2 proof of concept study evaluating the dual-agonist (SAR425899) in overweight and obese type 2 diabetic patients confirmed SAR425899 is a potent hypoglycemic agent and can induce significant weight loss … However, the gastrointestinal tolerability observed with the dose escalation regimen used in the study is not considered to be acceptable for clinical use. An additional study was initiated in the first quarter to explore alternative titration regimens to facilitate improved tolerability and adherence and is expected to read-out in 2018.”

In a call with analysts this morning, Sanofi’s outgoing R&D head, Elias Zerhouni, M.D., gave a little more color, saying: “We had two significant primary endpoints we needed to achieve on the efficacy side, and we actually hit more than our minimal primary endpoint of the GLP-1 reduction of HbA1c.”

That’s the good news, here's the bad: “The true issue is tolerability, and drop out of a quarter of the patients, because of the tolerability issues. We had a higher GLP-1 effect in the molecule than we expected from our non-human primate data, and we think that the titration was too abrupt and so that’s what we’re working on.”

He said that’s the focus of the trial they are doing now. “We have very innovative imaging studies, so that by the early summer, around June, we will know a lot better [how the dosing test is doing].”

RELATED: Sanofi hires ex-Roche executive John Reed to replace retiring Elias Zerhouni as R&D chief

Of course, this is around the time the time Zerhouni will retire from Sanofi (specifically, July 1), to be replaced by Roche pRED veteran John Reed, M.D., Ph.D., who left the Swiss major last month.

As we near that date, analysts took the opportunity to ask Zerhouni what went well during his tenure, and what didn’t work out so great.

“On the ‘what went well list’, do you have enough time?” he joked. “No, OK well frankly the best thing we were able to do was to re-shape the R&D organization; it was very fragmented and we were able to bring it down to just three major sites: Boston, Paris and Frankfurt and reduce headcount sufficiently to free up resources to do what we needed to do.”

He also points to “partnering well” to top up its “empty pipeline,” which he sees as being “outstandingly executed on,” which also saw it boost productivity during his 2009 to 2018 tenure, calling it a “good turnaround in terms of execution.” He says that, overall, the R&D side is now “more functional,” where it wasn’t before.

He also notes the turn to biologics, as when he started it was a completely small molecule-focused firm. He said it’s good today “but not great,” and it needs to continue on that path.

He also pointed to having “top talent,” which includes his successor Reed, who he says must see a lot of potential in Sanofi, “otherwise he wouldn’t be coming here.”

And what didn’t go so well? “The length of time to do the social planning in Europe; it takes a long time and it affects research operations, so we weren’t done with that process until 2015 and in research, it takes a long time to mature, so I wish that had gone faster.”

He also pointed to undisclosed external targets that he “wished we’d picked” over the years. He thought those projects were exciting, but they were hamstrung by patent losses that reduced money they could spend on these assets.

And finally, analysts asked whether a large M&A deal was off the table, given its recent buys of Bioverativ and Ablynx. Its CEO Olivier Brandicourt said: “In the near term, we’re focusing on integrating the two companies we just purchased … that’s going to require a lot of attention and focus, for now.”

He added that there was still some cash left over for potential bolt-on deals.