Not all drugs have an easy path to market, and an FDA rejection can hit hard. For Lexicon Pharmaceuticals, the hits keep coming, in the form of two rejections and a disappointing adcomm for its type 1 diabetes and chronic kidney disease candidate sotagliflozin.
The FDA first rejected sotagliflozin for type 1 diabetes patients in 2019, when Lexicon was partnered with Sanofi on the drug. The pharma giant subsequently ducked out of the partnership via a $260 million payment to Lexicon. Then, the biotech lost a bid for an appeal the following year, but still the company continued to develop sotagliflozin, which was approved in the EU for as an adjunct treatment to insulin in type 1 diabetes and launched with the brand name Zynquista.
But Lexicon’s ongoing bid to expand into the U.S. type 1 diabetes market was dealt a third blow last week when an advisory committee voted against the drug for approval. While the adcomm’s decision is non-binding, the agency was in agreement 88% of the time between 2010 and 2021, and the result highlights a lack of faith in the beleaguered drug. Lexicon CEO Mike Exton found a silver lining when committee experts agreed there was an urgent need for this patient group, but they ultimately decided there was not enough data to prove the drug’s benefits outweighed the risks.
“We are disappointed in the outcome of today’s advisory committee vote,” Exton said in a statement. “However, we were encouraged by the rich discussion and outpouring of support across the diabetes community in favor of sotagliflozin being made available to appropriate people with [type 1 diabetes] and [chronic kidney disease].”
Market opportunities
The company announced earlier this year that it was cutting about half of its “field force” as part of a $40 million cost-saving effort to prepare for the drug’s launch.
It’s a tough pill to swallow with a market opportunity upwards of $400 million for the patient group, according to some estimates. Other estimates had projected sotagliflozin could reach $1 billion in sales.
Lexicon maintains that sotagliflozin would be the only adjunct therapy to insulin for patients with type 2 diabetes and chronic kidney disease if approved. The patient need is also high, as only 20% of type 1 diabetes patients can maintain adequate glycemic control with just insulin, Dr. Steve Edelman, professor of medicine at the University of California, San Diego, and founder and director of Taking Control Of Your Diabetes, said in Lexicon’s Oct. 31 release.
Zynquista is an oral SGLT1/SGLT2 inhibitor that already has legs in other indications. But after its EU approval, its marketing authorization was withdrawn in 2022 after Guidehouse Germany, which held the marketing rights, decided not to market the drug.
When the FDA rejected Zynquista in 2019, advisory committee members were split, voting 8-8. This time, with an 11-3 vote, Lexicon’s path to the finish line in type 1 diabetes is even rockier.
The company expects the FDA to render a decision on Dec. 20.
Heart failure hopes
Lexicon last year secured an FDA approval in heart failure for sotagliflozin, sold under the brand name Inpefa for the indication, as well as for some type 2 diabetes patients with cardiovascular risks. Inpefa is the company’s only approved drug on the U.S. market, but it has yet to pick up sales traction. During the second quarter of 2024, Lexicon reported $1.6 million in sales and $1.1 million in the first three months of the year.
There’s likely some upside on the way. Last month, Lexicon penned a $25 million deal with generics giant Viatris for the rights to sell Inpefa outside the U.S. and Europe, with Lexicon retaining some royalty rights. The company is still far from reaching projected sales of $112 million by 2025 and $576 million by 2028, Reuters reported last year.
Lexicon’s Inpefa is also facing Big Pharma competition. Boehringer Ingelheim and Eli Lilly’s Jardiance is also an SGLT2 inhibitor approved for reducing cardiovascular risk in type 2 diabetes patients, as well as heart failure and chronic kidney disease — the same indications where Lexicon is looking to make headway. Jardiance has been a smash success, raking in $8 billion in sales in 2023, Boehringer Ingelheim reported. And the drug is so widely used it landed on the first 10 drugs in Medicare’s newly established drug price negotiation program, which will take effect in 2026.
Beyond type 1 diabetes, the company is undertaking phase 3 testing for a hypertrophic cardiomyopathy indication for sotagliflozin. Elsewhere in the pipeline, Lexicon has a phase 2 candidate for diabetic peripheral neuropathic pain and a preclinical obesity asset.
