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FDA Reiterates the Rejection of Lexicon Pharmaceutical’s Diabetes Drug Sotagliflozin (Zynquista™)

09 Dec FDA Reiterates the Rejection of Lexicon Pharmaceutical’s Diabetes Drug Sotagliflozin (Zynquista™)

Lexicon Pharmaceuticals (NASDAQ: LXRX), a biopharmaceutical company leveraging its proprietary Genome5000™ program to develop therapeutics for the treatment of disease such as diabetes, metabolism, oncology and neuropathic pain, announced that the Food and Drug Administration (FDA) has reiterated its rejection of the Company’s New Drug Application for sotagliflozin (Zynquista™), an oral dual inhibitor sodium-glucose co-transporter types 1 and 2 (SGLT1 and SGLT2), known to promote glucose regulation and intended for the treatment of Type I diabetes.

The FDA has earlier issued a complete response letter to the Company, owing to concerns about the drug’s safety, as late-stage clinical data showed an eight-fold increase in risk of diabetic ketoacidosis. The drug was a much anticipated alternative to the existing limited treatment options for Type I diabetes, and upon approval would have been the first oral drug used in combination with Insulin in the U.S. The Company had initially filed an application for the drug in March 2018 and was served a complete response letter in March 2019.

The Company intends to appeal the decision to the Center for Drug Evaluation and Research, or CDER, as per a Company Statement. However the chances of a reversal of stance by the FDA appear very slim. The European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP), on the other hand, has given a green signal for the drugs approval in Europe.

Sotagliflozin (Zynquista™) was jointly being developed by the Company in partnership with Sanofi (NASDAQ: SNY), which later terminated the partnership following the results from the late-stage studies testing Zynquista in patients with type 2 diabetes. As per the initial partnership agreement the Company had received $300 million in upfront payment and was due to receive another $1.4 billion in development, regulatory and sales milestone payments.

Lexicon Pharmaceuticals (NASDAQ: LXRX)

Market Cap: $513.56M; Current Share Price: 4.23 USDChart
Data by YCharts

Diabetes is a silent killer which is slowly reaching endemic proportions in developed as well as developing countries. The rise in obesity, sedentary lifestyles, poor dietary choices, stress and lack of exercise will see the number of incidences of Diabetes rise in the future. According to the International Diabetes Federation, the number of people living with diabetes will rise to 629 million by 2045, from 425 million adults (20-79 years) in 2017. In the U.S alone the people living with diabetes are set to increase from 58 million in 2017 to 67 million by 2045.

The increased awareness about the long-term complications caused by diabetes, along with the rise in co-morbidities such as cardiovascular, renal and neuropathic complications is set to propel the growth in the segment from $26.8 billion in 2016 to around $64 billion by 2026 according to a research by GlobalData. In spite of the market being dominated by generic drugs, such as metformin and similar drugs being in developmental stage, the market is projected to achieve a CAGR of 8.4% as per the same report.

Image Source: Company

Metformin is the first line of treatment adopted by doctors due to its minimal long-term side-effect profile, while there are other treatment options available such as sulfonylureas (SUs), these are being replaced by therapeutics involving DPP-4Is , GLP-1RAs, SGLT-Is which have a far safer side-effect profile and other benefits such as improved cardio vascular health, weight loss etc. The industry has a huge unmet potential for novel patented products that can overcome the limitations of existing therapeutics options.

Lexicon Pharmaceuticals leverages its proprietary Genome5000™ program, based on a Nobel Prize winning technology, to develop therapeutics for chronic conditions. Using a systematic approach, the Company has generated over 100 protein targets that exhibit significant potential in numerous diseases.

The Company manufactures XERMELO, which is a first-in-class oral therapeutic for Carcinoid Syndrome Diarrhoea, indicated to be used along with Somatostatin analog (SSA) therapy in adult patients who are not adequately controlled by SSA therapy. Lexicon is primarily focussed on four most advanced drug programs namely Telotristat ethyl, indicated  for the treatment of biliary tract cancer; Zynquista™ (sotagliflozin),approved in the European Union for type 1 diabetes; Sotagliflozin, for type 1 and type 2 diabetes; LX2761, for treatment of diabetes; and LX9211, for treatment of neuropathic pain, as per the Company.

Image Source: Company

Lexicon has established strategic collaborations with Ipsen (OTCPINK: IPSEF), granting it an exclusive, royalty-bearing right and license to commercialize XERMELO outside of the United States, Canada and Japan, in exchange for $24.5 million in upfront payments and $20.5 million in regulatory and commercial launch milestones, besides another $11.8 million upon the achievement of additional specified regulatory and commercial launch milestones and up to €72 million upon the achievement of specified sales milestones as per the Company.

In addition the Company also has agreements with Bristol–Myers Squibb (NYSE: BMY) for LX9211 and Genentech for advanced research, development and commercialization of new biotherapeutic drugs.

Recently the Company reported positive topline data from a phase I study of LX9211, a potent oral small molecule inhibitor of adaptor associated kinase 1 (AAK1), in development for the treatment of neuropathic pain.

Risk Assessment

  • The Company has been facing multiple setbacks, for instance its drug product Xermelo, indicated for the treatment of carcinoid syndrome diarrhea, was expected to bring in peak annual sales of up to $350 million, however as per its financial statement, the drug could only muster $24 million in sales during the first nine months of 2019.
  • The Company received a termination payout of $260 million from Sanofi, which will provide the funds necessary to complete its late-stage studies for Zynquista in type 2 diabetes along with regulatory approvals in U.S and Europe. However the Company does not have sufficient cash, as admitted by the management, to carry two late-stage clinical trials that are evaluating Zynquista in cardiovascular and renal function.
  • The SGLT2 inhibitors market offers tough competition with players such as Eli lilly (NYSE: LLY) and Boehringer (Jardiance), Astra Zeneca (NYSE: AZN)  (Farxiga) and Merck (NYSE: MRK) and Pfizer (NYSE: PEE) that offer Steglatro, although Zynquista will be a first-in-class dual inhibitor targeting both SGLT1 and SGLT2, it may find it difficult to wrestle market share from the already established players.
  • Lexicon is seeking partners to develop and fund it pipeline, however it may face challenges considering the potential of Zynquista can only be fully evaluated once the Company is able complete the cardiovascular studies and shows a reduced risk in cardiovascular events or death before any other player does, which seems unlikely as it still does not have a partner and its competitors Merck and Pfizer, which offer Steglatro, are likely to report results from ongoing clinical trials by the end of 2019.
  • Disclosure: I/we have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.

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