Memorandum

FDA Advisory Committee Meeting to review Sanofi/Lexicon’s sotagliflozin in type 1 announced for January 17, 2019 – November 30, 2018

Executive Highlights

  • Lexicon announced yesterday that FDA will convene an Advisory Committee on January 17, 2019 to review partner Sanofi’s NDA for sotagliflozin as an adjunct therapy for adults with type 1 diabetes. The NDA for sotagliflozin was first submitted to FDA by Sanofi in March 2018, accepted in May 2018, and assigned a PDUFA date of March 22, 2019. Sanofi/Lexicon strongly anticipated an Ad Comm to come in early 2019, and we’re glad to have such advance notice of the meeting.

  • This news comes on the heels of a recent, private EMA/CHMP meeting in Europe, during which the EU agency weighed the potential approval of SGLT inhibitors for type 1 diabetes (both sotagliflozin and dapagliflozin). Because it was completely closed off to the public, the discussion and outcomes from the meeting are still shrouded in uncertainty. However, our current understanding is that a formal decision from EMA/CHMP will be withheld until after this Ad Comm meeting for sotagliflozin.

Lexicon announced yesterday that FDA will convene an Advisory Committee on January 17, 2019 to review Sanofi-partnered SGLT-1/2 dual inhibitor sotagliflozin for adults with type 1 diabetes. The NDA for sotagliflozin was first submitted to FDA by Sanofi in March 2018 and accepted for review in May 2018. FDA’s PDUFA (target decision) date remains March 22, 2019, giving up to two months of review time following discussions and data to be presented at Ad Comm. This is slightly more notice than usual for an Ad Comm, and we’re hopeful that FDA will be able to release briefing documents earlier than usual, as well, given that they welcome patients at the meeting who will need longer to read the documents. In real life, we’d be very surprised to have more than two business days’ notice but we hope we will.

An Advisory Committee was a near-certainty for sotagliflozin. Lexicon and Sanofi management have been expecting and preparing for one (at least) since the NDA was submitted in March 2018, and the date of January 17, 2019 aligns with Lexicon’s long-predicted timeline of “early 2019”. We did think it could make sense for FDA to hold a combined Ad Comm for sotagliflozin and AZ’s Farxiga (dapagliflozin) for type 1, but AZ submitted the sNDA for this indication much later in the US (acceptance for review expected 4Q18, per the company’s 3Q18 update) so from a competitive perspective that may be considered less fair.

This news comes on the heels of a recent, private EMA/CHMP meeting in Europe, during which the EU agency weighed the potential approval of SGLT inhibitors for type 1 diabetes (both sotagliflozin and dapagliflozin). Because it was completely closed off to the public, the discussion and outcomes from the meeting are still shrouded in uncertainty. However, our current understanding is that a formal decision from EMA/CHMP will come sometime after this Ad Comm meeting for sotagliflozin. If we had to bet, we’d bet it would be positive, given the outsized risk for allowing so many patients with type 1 to take a drug in unregulated fashion, but this is based on speculation only.

DKA risk will surely dominate much of the discussion at this Ad Comm meeting, and for good reason. Throughout the inTandem program, incidence of DKA was higher in the sotagliflozin arm when compared to placebo. For example, there were 21 vs. 4 events in inTandem3, though only 400 mg sotagliflozin was tested and only 3% of participants in that arm experienced DKA. While the risk is low, though, DKA is a very serious and costly complication. Increased DKA is broadly considered a class risk of SGLTs in type 1, and it has also emerged in other programs, including DEPICT for dapagliflozin and EASE for empagliflozin. Importantly, FDA’s decision making on sotagliflozin will undoubtedly set the tone for the entire class’ future in type 1 diabetes.

We’ll be curious to see how Sanofi/Lexicon aim to balance efficacy and DKA risk to FDA and the Ad Comm. Lexicon has highlighted the anticipated publication of consensus guidelines for DKA risk management in early 2019 (presumably before the Ad Comm meeting date but we don’t know for sure). Moreover, Lexicon has indicated that the companies may focus on demonstrating specific benefits on postprandial glucose and hypoglycemia risk. It will be essential to drive home the value – especially on time-in-range and weight loss – that sotagliflozin offers type 1s. Lexicon CEO Mr. Lonnel Coats has previously confirmed that CGM data from the inTandem program was submitted as part of sotagliflozin’s NDA, and we’re hopeful that FDA will strongly consider these data and recognize they benefit they represent.

To be sure, the three-plus years long movement toward approval of SGLT inhibitors for type 1 patients is reaching a crucial moment – see our recent reflections on the history and landscape of this movement here. We’ll be back with more as further information is released regarding the Advisory Committee meeting.

 

--by Martin Kurian, Ann Carracher, and Kelly Close