Lexicon's type 1 diabetes drug voted down by FDA adcomm

It has been five years since Lexicon Pharma's type 1 diabetes therapy, Zynquista, was rejected by the FDA, and it may struggle to have a better outcome at its second attempt.

An FDA advisory committee voted by 11 to three against approval of the dual SGLT1/2 inhibitor as an adjunct to insulin therapy for glycaemic control in adults with T1D and chronic kidney disease (CKD) on the grounds that its benefits do not outweigh its risks.

It is an even worse outcome for Lexicon than the panel's vote in 2019, which was split at eight to eight and was followed shortly after by a complete response letter (CRL) from the FDA. At the time, Lexicon was going after a broader label across all type 1 diabetes patients, which was scuppered by concerns about a side effect known as diabetic ketoacidosis (DKA).

The decision was appealed twice by the company without success and – a few months later – Lexicon's former partner for Zynquista (sotagliflozin) handed back rights to the drug in exchange for a $260 million termination fee. Sanofi and Lexicon had partnered on the drug in 2015 in a deal valued at up to $1.7 billion.

Lexicon did manage to get approval for type 1 diabetes in Europe, but the product was never launched there for commercial reasons. Meanwhile, it did secure FDA approval for sotagliflozin under the Inpefa band name last year for use in patients at risk of heart failure.

While approval prospects look shaky once again, Lexicon has taken some comfort from comments made by some of the panellists that Zynquista could have a role to play in certain sub-populations of people with type 1 diabetes and CKD – potentially opening up a route to FDA approval.

Specifically, that included patients with a kidney function score of 60 to less than 90 or those who have mild to moderate kidney disease. Other panellists suggested, however, that the numbers of patients in these categories were too small to make an informed judgment.

"We are disappointed in the outcome of today's advisory committee vote. However, we were encouraged by the rich discussion and outpouring of support across the diabetes community in favour of sotagliflozin being made available to appropriate people," said Dr Mike Exton, Lexicon's chief executive.

The FDA is scheduled to deliver its verdict on the application by 20th December.

"It's clear from today's discussion that an FDA-approved treatment and clear education on managing risk is urgently needed, and we believe our data supports this need."

Earlier this month, Lexicon licensed all ex-US rights to sotagliflozin – across all its potential indications – to Viatris in return for an upfront payment of $25 million plus royalties on sales.

In August, it said it was taking the strategic decision to focus all its efforts on the commercialisation of Inpefa and the potential launch of Zynquista, slashing 50% of its workforce to trim $40 million off its costs.