It’s been a winding road full of potholes, but Lexicon Pharmaceuticals has finally reached its destination, gaining an FDA approval for Inpefa (sotagliflozin).
The once-daily pill becomes the first SGLT1/SGLT2 inhibitor to reach the market. It has been sanctioned to reduce the risk of heart failure in adults who have had the condition or have Type 2 diabetes, chronic kidney disease and other cardiovascular risk factors.
Lexicon expects Inpefa to become available by the end of June and will price it “comparable to existing heart failure medications,” the company said.
The green light comes for a treatment that has shown tantalizing potential with its ability to block SLGT2 in the kidneys and SLGT1 in the intestines. Negotiating regulatory hurdles in the U.S., however, has been problematic.
In 2019, following an 8-8 vote from an advisory committee, 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 patients. Last year, the holders of Zynquista’s marketing rights in Europe, Guidehouse Germany GmbH, withdrew (PDF) the marketing authorization, saying it did not wish to commercialize the product.
Then, last year, as Lexicon approached its bid to treat heart failure in Type 2 patients, the company yanked its application to work through what it termed “technical issues.” Friday, the FDA agreed those had been resolved.
“There’s been a lot of air traffic control going on,” Craig Granowitz, M.D., Ph.D., the company’s chief medical officer, said in an interview with Fierce Pharma last week. “They were largely paperwork-related, not substantive clinical issues on efficacy or safety. And I think the evidence has borne that out, with the speed and few issues that have come up in the FDA review.”
In expressing his confidence that Lexicon would win an approval, Granowitz also noted that the FDA did not conduct an inspection or require the company to justify its risk-benefit profile in an advisory committee meeting.
Another positive sign came earlier this year when the American College of Cardiology revised its guidelines for treating patients with heart failure with preserved ejection fraction, recommending three SGLT2 drugs—one of them being sotagliflozin.
The FDA nod is based on two placebo-controlled phase 3 cardiovascular outcomes studies in patients with heart failure or at risk of it. Together, SOLOIST-WHF and SCORED enrolled almost 12,000 patients. Results from SOLOIST-WHF showed that Inpefa significantly reduced risk of hospitalizations for heart failure, urgent visits for heart failure and cardiovascular death by 33% compared with placebo in patients who had been recently hospitalized for worsening heart failure.
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.
Both have been on the market for nearly a decade, but Granowitz believes Inpefa can make its mark.
“I came here (in 2021) because I was so excited and passionate about heart failure,” Granowitz said. “And why I thought sotagliflozin could make a difference on top of the SGLT2 inhibitors that were already out there. Every step of the way has reinforced that perspective.”
In the U.S., heart failure sends approximately 1.3 million people to the hospital each year and is the leading cause of hospitalizations for people 65 and older. About 6.7 million Americans suffer from the condition, with the prevalence expected to rise to 8 million by 2030.
“Inpefa is now a valuable option for physicians to consider when treating patients transitioning out of the hospital and working to break the cycle of repeated hospitalizations,” Granowitz said in a release.
It’s a much-needed win for a company that reported $139,000 in revenue last year, a 53% drop from 2021. With the prospect of this approval looming, the price of Lexicon’s shares has risen this year from $1.99 to $3.18.
Now it is on for the Texas-based company to gain an approval in Type 1 diabetes.
In 2015, the potential of sotagliflozin was recognized by Sanofi, which ponied up $300 million for a piece of it and committed $1.4 billion in possible milestone payments. When the first FDA rejection came however, the French powerhouse paid Lexicon $260 million to exit the partnership. That funding has helped keep Lexicon afloat in its efforts to get Inpefa to the market.