Lexicon slams FDA over hearing denial following a CRL for its SGLT2 inhibitor candidate
Lexicon Pharmaceutical is not giving up on its Type I diabetes candidate, despite FDA’s repeated rejections. This week the company laid out is argument again for a hearing on sotagliflozin in response to the FDA’s most recent denial.
The issue goes back to March 2019 when the FDA made very clear to Lexicon and its now departed partner Sanofi that it would not approve their application for a potential Type I diabetes drug because it does not appear to be safe.
“The data demonstrated that the addition of sotagliflozin to insulin is associated with an increased risk of diabetic ketoacidosis (DKA), a serious and often life-threatening consequence of insulin insufficiency,” the agency said in a rare explanation of its complete response letter. “Time-to-event analyses of the clinical trial data showed earlier development of DKA in sotagliflozin-treated patients than in patients assigned to placebo, without evidence that the risk stopped increasing over time.”
Unlike some of its larger peers that rarely challenge the FDA once multiple avenues to overturn the CRL have been denied, Lexicon remained determined, appealing the denial twice, and seeking a hearing in November 2021 to further discuss the application with outside experts.
The company claims that sotagliflozin is similar to other SGLT2 inhibitors that are already marketed, like Janssen’s Invokana and AstraZeneca’s Farxiga, adding:
CDER may not dismiss precedent by claiming that each case is different; these examples present a factual question regarding the extent of the benefits underlying the benefit-risk assessment, and ultimately, the approval of sotagliflozin. Treating similarly situated products differently, without adequate and reasoned explanation, is arbitrary and capricious in violation of the APA.
The clinical program for sotagliflozin, Lexicon contends, featured three large, multicenter, randomized Phase III trials, all of which achieved their pre-specified primary endpoints and demonstrated a statistically significant and clinically meaningful improvement in glycosylated hemoglobin (HbA1c) levels.
The company also says that the FDA’s concerns about the identified risk of DKA “can be adequately mitigated by risk mitigation tools that CDER has used to mitigate similar risks in other diabetes products. DKA is not an insignificant risk; however, it is a risk that is endemic to T1DM and not unique to sotagliflozin.”
Moving forward, according to an agreement made between the FDA and Lexicon in September, if CDER continues to recommend that the FDA’s Office of the Commissioner deny Lexicon’s request for a hearing, CDER shall submit Lexicon’s request for a hearing, Lexicon’s response, CDER’s analysis of Lexicon’s request for a hearing including any additional analysis by CDER of Lexicon’s response, and a proposed order denying the request for a hearing to the Office of the Commissioner by Jan. 31, 2023.