pilavapadin (LX9211) / Lexicon Pharma, BMS - LARVOL DELTA

Lexicon Pharmaceuticals Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Updates (GlobeNewswire) - "Pilavapadin (LX9211) for DPNP: The Company is moving toward an end of Phase 2 meeting with FDA and targeting initiation of U.S. and ex-U.S. Phase 3 trials in DPNP in 2025, while selecting a future medical meeting for release of additional clinical data later this year....LX9851 for Obesity and Associated Cardiometabolic Disorders: LX9851 is progressing in IND-enabling studies and on track for a 2025 investigational new drug (IND) application submission. Zynquista (sotagliflozin): Discontinued preparation for potential Zynquista launch in type 1 diabetes following receipt of complete response letter from FDA."

Discontinued • IND • New P3 trial • P3 data • Diabetic Neuropathy • Obesity • Peripheral Neuropathic Pain • Type 1 Diabetes Mellitus

Lexicon Pharmaceuticals Announces Topline Results from Phase 2b PROGRESS Study Evaluating Pilavapadin (LX9211) in Adults with Diabetic Peripheral Neuropathic Pain (GlobeNewswire) - P2b | N=416 | PROGRESS (NCT06203002) | Sponsor: Lexicon Pharmaceuticals | "In the PROGRESS study, all pilavapadin treatment arms demonstrated reductions in the mean average daily pain score (ADPS) from baseline to Week 8 with the 10 mg, 20 mg/10 mg and 20 mg dose arms achieving reductions of 1.74, 1.70 and 1.38, respectively, compared to a reduction of 1.31 in the placebo arm...As a result of the lack of separation in ADPS reduction between the 20 mg dose arm and placebo, the study results did not reach statistical significance on the primary endpoint (p=0.11). However, the 10 mg dose arm demonstrated clear evidence of effect by achieving early and clinically meaningful separation from placebo on ADPS that was maintained throughout the study duration. Adverse events were more frequent in the pilavapadin treatment arms, but were significantly improved from the RELIEF-DPN-1 study across all doses. Nearly all adverse events were reported as mild or moderate."

P2b data • Peripheral Neuropathic Pain

Lexicon Pharmaceuticals to Announce Topline Results from Phase 2b PROGRESS Study Evaluating Pilavapadin (LX9211) in Adults with Diabetic Peripheral Neuropathic Pain (GlobeNewswire) - "Lexicon Pharmaceuticals...announced the Company will hold a conference call and webcast on Monday, March 3, 2025 at 8:00 a.m. ET to share topline results from the Phase 2b PROGRESS (A Phase 2b, Dose-ranging, Randomized, Double-blind, PlacebO-controlled, Parallel-GRoup, MulticEnter Study with an Open-label Extension in PatientS with Diabetic Peripheral Neuropathic Pain) study evaluating pilavapadin (LX9211), an oral, non-opioid investigational adaptor-associated kinase 1 (AAK1) inhibitor in adult patients with moderate to severe diabetic peripheral neuropathic pain (DPNP)."

P2b data • Diabetic Neuropathy • Peripheral Neuropathic Pain

LX9211, a rising star for relieving of diabetic peripheral neuropathic pain. (PubMed, J Diabetes Investig) - "Although the higher dose was less effective, side effects like dizziness and nausea were generally mild. These findings highlight the importance of exploring both pharmaceutical and natural treatments, such as flavonoids, for managing DPN."

Journal • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Lexicon Announces Virtual Webcast on LX9211 for Diabetic Peripheral Neuropathic Pain (GlobeNewswire) - "Lexicon Pharmaceuticals...today announced that the company will host a virtual webcast...The event will be held from 9:00 a.m. to 11:00 a.m. ET on January 28, 2025...In advance of topline data from the Phase 2b PROGRESS trial anticipated later this quarter, the event will offer an in-depth overview on LX9211 for the treatment of diabetic peripheral neuropathic pain (DPNP), featuring remarks from Lexicon leaders....In addition to presentations by the Lexicon leadership team, the event will include an expert panel and Q&A session on DPNP..."

Clinical • P2b data • Pain • Peripheral Neuropathic Pain

Lexicon Announces Receipt of Complete Response Letter for Zynquista (sotagliflozin) (GlobeNewswire) - "Lexicon Pharmaceuticals...announced it has received a complete response letter (CRL) from the U.S. Food and Drug Administration (FDA) regarding the New Drug Application (NDA) for Zynquista (sotagliflozin) as an adjunct to insulin therapy for glycemic control in adults with type 1 diabetes and chronic kidney disease (CKD). This expected communication from the FDA aligns with the company’s previously disclosed strategic decision to discontinue launch preparations for Zynquista and focus solely on its clinical development pipeline....'We remain steadfast in our commitment to advancing our clinical pipeline, including our near-term focus on LX9211 for diabetic neuropathic pain (DPNP) with top line data from our PROGRESS Phase 2b study anticipated in Q1 2025'."

CRL • P2b data • Chronic Kidney Disease • Diabetic Neuropathy • Peripheral Neuropathic Pain • Type 1 Diabetes Mellitus

Discovery and evaluation of HW161023 as a potent and orally active AAK1 inhibitor. (PubMed, Bioorg Med Chem Lett) - "LX9211 is currently the only selective small molecule AAK1 inhibitor at the clinical trial stage for diabetic peripheral neuropathic pain, which was found to be safe and well tolerated in healthy participants in phase I clinical trials. The present manuscript described a series of fused-ring derivatives as a novel class of potent AAK1 inhibitors, resulting in the discovery of compound 5, namely HW161023, which showed high inhibitory potency against AAK1 enzyme and satisfactory oral pharmacokinetic profile with weaker HepG2 cell toxicity and hERG inhibition than LX9211."

Journal • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

PROGRESS: A Dose-ranging Study in Patients with Diabetic Peripheral Neuropathic Pain (DPNP) (clinicaltrials.gov) - P2 | N=416 | Active, not recruiting | Sponsor: Lexicon Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Patient Reported Burden of Disease in Postherpetic Neuralgia Pain: Learnings from In-depth Patient Interviews, Sub-study of RELIEF-PHN-1 (PAINWeek 2024) - "LX9211, a potent, small molecule inhibitor of Adapter protein-2 Associated protein Kinase 1 (AAK1), is a novel, non-opioid target for the treatment of NP... Of the 19 patients interviewed, 9 (47%) were female, with a mean age of 67 years. On average, participants had been experiencing symptoms associated with PHN for 6 years. Eight descriptions of symptoms emerged from interview analyses."

Clinical • HEOR • Interview • CNS Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain

An overview of the safety and efficacy of LX-9211 in treating neuropathic pain conditions. (PubMed, Expert Opin Investig Drugs) - "In phase 1 and phase 2 clinical trials conducted so far, LX-9211 has been shown to produce few adverse effects as well as cause a significantly greater reduction in pain compared to placebo. However, more clinical studies are needed to further assess its effects in humans to ensure its safety."

Journal • Review • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Patient-Reported Burden of Disease in Diabetic Peripheral Neuropathic Pain—Learnings from In-depth Patient Interviews—Substudy of RELIEF-DPN 1 (ADA 2024) - "RELIEF-DPN 1, a Phase 2 study in adult patients with Type 1 or 2 diabetes and moderate to severe established DPNP, evaluated the safety and efficacy of LX9211, a potent non-opioid inhibitor of AP2-associated protein kinase 1 (AAK1)... This sub-study demonstrates that, from patients' perspectives, symptoms and aspects of daily living impacted by DPNP are considerably burdensome to patients. This study highlights a pressing need for improved therapy and innovation in DPNP management."

Clinical • HEOR • Interview • Diabetic Neuropathy • Metabolic Disorders

Efficacy and Safety of LX9211 for Relief of Diabetic Peripheral Neuropathic Pain (RELIEF-DPN 1): Results of a Double-Blind, Randomized, Placebo-Controlled, Proof-of-Concept Study. (PubMed, Diabetes Care) - "These preliminary findings of improvement in DPNP with LX9211 support further investigation in larger trials."

Journal • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Data From Lexicon’s RELIEF-DPN 1 Phase 2 Study of LX9211 Published Today in Diabetes Care, a Peer-Reviewed Journal of the American Diabetes Association (GlobeNewswire) - P2 | N=319 | RELIEF-DPN 1 (NCT04455633) | Sponsor: Lexicon Pharmaceuticals | "Lexicon Pharmaceuticals, Inc...has published a research paper on the company’s Phase 2 RELIEF-DPN-1 clinical trial investigating LX9211 for the treatment of diabetic peripheral neuropathic pain (DPNP)....The primary efficacy endpoint under evaluation was the change from baseline to week 6 in average daily pain score (ADPS), which was achieved for subjects participating in the low-dose LX9211 arm. Patient reported outcomes were improved in patients treated with LX9211 and LX9211 was generally well tolerated....An abstract of a Lexicon-sponsored study...will be presented at the 84th Scientific Sessions of the American Diabetes Association on Sunday, June 23, 2024, 12:30 - 1:30 p.m. ET, in the Poster Hall (West A-4-B2), Board No. 484."

P2 data • CNS Disorders • Diabetic Neuropathy • Pain • Peripheral Neuropathic Pain

Findings on the Burdens of Diabetic Peripheral Neuropathic Pain (DPNP) Among Three Lexicon-Sponsored Presentations at the 84th Scientific Sessions of the American Diabetes Association (Lexicon Press Release) - "Lexicon Pharmaceuticals, Inc...today announced that three poster presentations will be delivered during the 84th Scientific Sessions of the American Diabetes Association being held June 21 - 24, 2024 at the Orange County Convention Center in Orlando, Florida."

P2 data • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Lexicon Pharmaceuticals Selects Medidata to Help Advance First Non-Opioid Drug for Neuropathic Pain in Over Two Decades (Businesswire) - "Medidata...announced today that it has been selected by Lexicon Pharmaceuticals, Inc. to help advance PROGRESS, a Phase 2b study of LX9211 in diabetic peripheral neuropathic pain (DPNP), with the potential for LX9211 to become the first new, non-opioid drug approved for neuropathic pain in over two decades. Medidata will enable Lexicon to accelerate patient enrollment and clinical trials for Lexicon’s AAK1 inhibitor LX9211, improving the patient experience with a focus on addressing the high, unmet need for chronic neuropathic pain therapies."

Commercial • Diabetic Neuropathy • Pain

From mouse to man: Discovery and development of LX9211, an AAK1 inhibitor for neuropathic pain | Poster Board #1907 (ACS-Sp 2024) - "This presentation will cover the discovery, synthesis, and clinical development of LX9211 which is now entering a Phase 2b dose optimization study. LX9211 has received Fast Track designation from the U.S. Food and Drug Administration for development in DPN."

Preclinical • Diabetic Neuropathy • Neuralgia • Pain

Design, synthesis and biological evaluation of novel 1,2,4a,5-tetrahydro-4H-benzo[b][1,4]oxazino[4,3-d][1,4]oxazine-based AAK1 inhibitors with anti-viral property against SARS-CoV-2. (PubMed, Eur J Med Chem) - "The results revealed that 12e was superior in vitro antiviral activity against SARS-CoV-2 entry into host cells when compared to SGC-AAK1-1 and LX9211, and its activity was comparable to that of a related and reference compound 8...Notably, compounds 8 and 12e exhibited a more potent effect in suppressing the phosphorylation of AP2M1 T156 and the interaction between AP2M1 and ACE2. In conclusion, novel AAK1 inhibitor 12e demonstrates significant efficacy in suppressing SARS-CoV-2 infection, and holds promise as a potential candidate for developing novel antiviral drugs against SARS-CoV-2 and other coronavirus infections."

Journal • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • AP2M1 • TFAP2A

PROGRESS: A Dose-ranging Study in Patients With Diabetic Peripheral Neuropathic Pain (DPNP) (clinicaltrials.gov) - P2 | N=416 | Recruiting | Sponsor: Lexicon Pharmaceuticals | Enrolling by invitation ➔ Recruiting

Enrollment status • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Asymmetric Phase-Transfer Alkylation of Readily Available Aryl Aldehyde Schiff Bases of Amino Acid Ethyl Esters. (PubMed, Org Lett) - "Asymmetric phase-transfer alkylation of the N-(arylmethylene)-α-alkylamino acid ethyl esters and N-(arylmethylene)glycine ethyl esters was found to be catalyzed by the (R)- or (S)-Simplified Maruoka Catalyst with high efficiency and excellent enantioselectivity. This approach was successfully applied to the enantioselective formal synthesis of the angiotensin II type 2 receptor (AT2R) antagonists Olodanrigan and LX9211, and the practical aspect is demonstrated by the kilogram-scale synthesis of a key intermediate for the synthesis of LX9211."

Journal

PROGRESS: A Dose-ranging Study in Patients With Diabetic Peripheral Neuropathic Pain (DPNP) (clinicaltrials.gov) - P2 | N=416 | Enrolling by invitation | Sponsor: Lexicon Pharmaceuticals

New P2 trial • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Lexicon Enrolls First Patient in Phase 2b Progress Study of LX9211 in Diabetic Peripheral Neuropathic Pain (DPNP) (GlobeNewswire) - "Lexicon Pharmaceuticals, Inc...today announced that it has enrolled the first patient in PROGRESS...studying LX9211, a potent, orally-delivered, selective, investigational small molecule inhibitor of adaptor-associated kinase 1 (AAK1). PROGRESS will enroll adult patients with a diagnosis of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) with moderate to severe DPNP. The primary endpoint of PROGRESS is a reduction of Average Daily Pain Score (ADPS), consistent with the primary endpoint achieved in the successful RELIEF-DPN-1 Phase 2a proof-of-concept study and, informed by regulatory feedback, the primary endpoint planned for Phase 3 studies of LX9211 in DPNP....Topline data from PROGRESS is expected to be announced in Q2 2025."

Enrollment open • P2b data • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Lexicon Pharmaceuticals Reports Third Quarter 2023 Financial Results and Provides Business Update (Yahoo Finance) - "Research and Development (R&D) Expenses: Research and development expenses for the third quarter of 2023 increased to $17.6 million from $10.6 million for the corresponding period in 2022, primarily due to higher manufacturing costs and higher external research and development expenses related to the LX9211 program, partially offset by lower professional and consulting fees."

Commercial • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Lexicon to Present Study Results Relating to Sotagliflozin and LX9211 at the 59th Annual Meeting of the European Association for the Study of Diabetes (EASD) (GlobeNewswire) - "Lexicon Pharmaceuticals, Inc...today announced several upcoming Lexicon-supported data presentations related to heart failure (HF), type 1 diabetes (T1D), and diabetic peripheral neuropathic pain (DPNP). The oral presentations will be made at the 59th Annual Meeting of EASD, October 2-6, 2023, in Hamburg, Germany and online. "

Clinical data • P2 data • CNS Disorders • Diabetes • Diabetic Neuropathy • Metabolic Disorders • Neuralgia • Pain • Peripheral Neuropathic Pain • Type 2 Diabetes Mellitus

LX9211 in individuals with painful diabetic peripheral neuropathy: results from a randomised, double-blind, placebo-controlled, parallel-group, multicentre study (EASD 2023) - P2 | "RELIEF-DPN 1 demonstrated significant improvements in validated neuropathic pain instruments and in other patient reported outcomes suggesting that LX9211 is a promising, opioid independent new avenue to treat people with painful DPN. Confirmation of these positive results are planned in future Phase 3 trials"

Clinical • Diabetic Neuropathy • Metabolic Disorders

Lexicon Announces Series of Presentations Relating to LX9211, Its Investigational Drug for the Treatment of Diabetic Peripheral Neuropathic Pain (DPNP) (GlobeNewswire) - "Lexicon Pharmaceuticals, Inc...today announced a series of five upcoming scientific presentations on its investigational drug LX9211, which is being evaluated in clinical trials for the treatment of diabetic peripheral neuropathic pain (DPNP). Data will be shared through four oral presentations and one poster presentation at various global Congresses."

Clinical data • Trial status • CNS Disorders • Diabetic Neuropathy • Neuralgia • Pain • Peripheral Neuropathic Pain