SGLT1/SGLT2/DPP4 Inhibitor(Tonghua Dongbao Pharmaceutical Co., Ltd.)

Lexicon Pharmaceuticals' original Zynquista FDA rejection was in 2019. Since then, the company has persisted in its regulatory efforts. Ever since its first FDA rejection five years ago, Lexicon Pharmaceuticals hasn’t given up hope on its Type 1 diabetes prospect sotagliflozin. Now, the company’s approval dreams could be coming into focus as the drugmaker prepares to refile its application. After hearing recent regulatory feedback from the agency, Lexicon said it plans to submit the drug by the middle of the year, the company said in a press release. “We have remained steadfast in our support of sotagliflozin in type 1 diabetes and have worked diligently to identify a regulatory path forward for what we believe will be an important new therapy,” CEO Lonnel Coats noted in the release. Lexicon is hoping for an approval that clears the drug to be used as an add-on to insulin therapy for adults with Type 1 diabetes mellitus and chronic kidney disease, the company said in its fourth-quarter and full-year earnings presentation (PDF). If approved, the drug will be branded as Zynquista. Lexicon hit the first bump on its regulatory road in 2019, when the FDA rejected its bid with a safety-related complete response letter following a 8-8 vote from an advisory committee. At the time, Sanofi was partnered on the drug, but the French pharma jumped ship after the rejection and subsequent trial flops in Type 2 diabetes. In the rejection, the FDA cited concerns about the risk of diabetic ketoacidosis for patients taking insulin plus Zynquista. However, Lexicon maintains that the risk can be managed and may be outweighed by patients' unmet needs. Despite the FDA rejection, Zynquista was approved in Europe in 2019. Lexicon has a trove of phase 3 data proving Zynquista’s worth in diabetes with chronic kidney disease when paired with insulin, the company has said. The long-awaited nod would be highly beneficial to Lexicon, which took home $1.2 million in total 2023 revenues. Net losses for the year came out to $175.6 million. At one point, some analysts had blockbuster-level expectations for the drug. Meanwhile, the drugmaker has been able to take sotaglifozin into another indication. The med scored approval for heart failure last year—branded as Inpefa—and launched weeks later, marking the first SGLT1/SGLT2 inhibitor to hit the U.S. market. The company is also testing the drug in hypertrophic cardiomyopathy.

Tom Garner is excited by Lexicon Pharmaceuticals' late-stage pipeline drug LX9211 to market for diabetic peripheral neuropathic pain. Lexicon Pharmaceuticals spent years jumping and often falling over regulatory hurdles for its new heart drug Inpefa, but, after finally getting an FDA approval this year, it’s now turning to Tom Garner to help shore up the drug’s launch. Garner has some real heart disease and pharma sales chops, having most recently been at Bristol Myers Squibb as its senior vice president and head of the company's U.S. Cardiovascular & Established Brands business unit. That included working on heart drug Eliquis, the most prescribed oral, branded medicine in the U.S., as well as Camzyos, a newly approved therapy for obstructive hypertrophic cardiomyopathy. He’s been at BMS for a mighty 21 years, having served stints at Boehringer Ingelheim and Eli Lilly before that stretch. His role at Lexicon will initially center on Inpefa, the once-daily pill that back in May became the first SGLT1/SGLT2 inhibitor to reach the market after getting an FDA green light. The med is now licensed to reduce the risk of heart failure in adults who have had the condition or have Type 2 diabetes, chronic kidney disease or other cardiovascular risk factors. It has been a winding and sometimes dark path for the drug to reach the finish line. In 2019, following an 8-8 vote from an advisory committee, what was then just known as sotagliflozin was rejected by the FDA to treat Type 1 diabetes patients who can’t control their blood sugar with insulin. A year later, when Lexicon appealed the decision, the regulator swatted it back again, citing the risk of diabetes ketoacidosis. In between the FDA rejections, regulators in Europe approved sotagliflozin as Zynquista for Type 1 diabetes patients. Last year, however, the holders of Zynquista’s marketing rights in Europe, Guidehouse Germany GmbH, withdrew the marketing authorization, saying it did not wish to commercialize the product. Then, as Lexicon approached its bid to treat heart failure in Type 2 patients in 2022, the company yanked its application to work through what it termed “technical issues,” though these were ultimately resolved.   Inpefa joins a strong field of SGLT2 inhibitors, including another that was approved earlier this year—TheracosBio’s Brenzavvy. Blockbusters that rule the market are Boehringer Ingelheim and Eli Lilly’s Jardiance, which generated sales of $6.1 billion in 2021, and AstraZeneca’s Farxiga, which rung up $4.4 billion in revenue last year. It will be a tough market battle, but one that Lexicon believes Garner can take on. “His overall breadth and depth of commercial and general management experience, with notable success in the cardiovascular space and leading launches, makes him a particularly valuable addition to our management team as we continue to drive the launch of Inpefa (sotagliflozin) for the treatment of heart failure,” said Lonnel Coats, Lexicon’s CEO, in a press release.“As the leader of our commercial organization, Mr. Garner will have a critical role in ensuring we are effectively executing on our launch strategy for Inpefa and delivering against the promise we believe this differentiated brand can have for patients." "I am very enthusiastic about joining the Lexicon leadership team and leading the commercial organization,” said Garner, adding that he is “particularly excited to leverage my expertise for the ongoing launch of Inpefa.” He is also eyeing the “potential opportunity” to bring Lexicon’s late-stage pipeline drug LX9211 to market for diabetic peripheral neuropathic pain. He said that the med “is what attracted me to Lexicon, and I cannot wait to step into this role and get started.”