EMA Confirms No Causal Link Between GLP-1 Weight-Loss Drugs and Suicidal Ideation

01

EMA stated on 2024-4-12, after a nine-month investigation, that they found no evidence suggesting that GLP-1 drugs such as Ozempic and Wegovy cause suicidal thoughts or behaviors. This statement by the EMA aligns with the preliminary findings of the U.S. FDA, which indicated in 2024-1 that there was no clear link between GLP-1 drugs and suicidal ideation.

02

On April 10, 2024, Ginkgo Bioworks, dedicated to developing leading cell programming and biosecurity platforms, announced the expansion of its strategic partnership with Novo Nordisk, a global healthcare leader, through a five-year framework agreement.

Novo Nordisk and Ginkgo Bioworks Create a Flexible and Scalable New Model for Their R&D Partnership

01

Recently, Lipocine announced positive results from the Phase II clinical trial of its investigational therapy LPCN 2401. Analysis showed that treatment with LPCN 2401 significantly increased lean mass (LM) and significantly reduced fat mass (FM) in obese or overweight patients with at least one weight-related comorbidity. According to the press release, LPCN 2401 has the potential to be used in combination with glucagon-like peptide-1 (GLP-1) drugs or as a monotherapy to maintain patient weight after discontinuation of such treatments.

In patients treated with options B and C, 27 subjects were randomly assigned and completed baseline and at least one post-baseline DEXA analysis. At baseline, the average BMI of the patients was 36.0 kg/m², and the average age was 52.4 years. Analysis showed that at 36 weeks, compared to placebo, treatment with LPCN 2401 increased patients' lean mass (LM) by 4.4% and decreased fat mass (FM) by 6.7%. Researchers observed significant improvements in body composition as early as week 20. Additionally, treatment with LPCN 2401 reduced abdominal fat (AF) by 4.1% and increased bone mineral content (BMC) by 2.8%. The drug treatment did not affect the patients' weight, as the reduction in fat was offset by an increase in lean body mass. Overall, treatment with LPCN 2401 significantly improved patients' body composition, substantially decreasing the fat mass/lean mass ratio. Moreover, compared to patients receiving treatment option A, LPCN 2401 resulted in a greater reduction in fat mass. After using LPCN 2401, patients showed trends of improvement in blood pressure and glycated hemoglobin levels.

Among them, LPCN 2401 is an oral medication with a proprietary formulation that combines an androgen receptor agonist and an antioxidant metabolic modulator, α-tocopherol. Preclinical and clinical study data indicate that LPCN 2401 has the potential to simultaneously reduce fat and increase muscle mass. As a potential adjunctive therapy to GLP-1 class drugs, LPCN 2401 is expected to mitigate weight rebound after discontinuation, improve declining muscle quality, and enhance muscle mass and function.

02

2024-4-10, researchers from leading health informatics company AMRA Medical, as well as Lilly and other institutions, used visceral, subcutaneous, and liver fat z-scores derived from MRI to study changes in fat distribution patterns in patients with type 2 diabetes (T2D) participating in the SURPASS-3 MRI trial.

The absolute (or percentage) change in body weight and/or BMI remains a typical endpoint for clinical trials assessing the treatment of obesity and related diseases. However, the research team recently discovered from the SURPASS-3 MRI study that drug treatments for T2D may alter fat distribution patterns in various ways, independent of changes in body weight. For this reason, fat distribution analysis through personalized z-score assessments will provide an attractive and modifiable endpoint for future clinical trials evaluating the efficacy of treatments for obesity and related diseases.

Exploratory Analysis of Lilly's SURPASS-3 MRI Study Data Describes Changes in Fat Z-Scores in T2D Patients After 52 Weeks of Once-Weekly Tirzepatide (5, 10, or 15 mg Dose) or Once-Daily Basal Insulin Degludec Treatment. Results Showed That Tirzepatide Treatment Was Associated With a Significant Reduction in Visceral Fat Z-Score (-0.18 SD) and Liver Fat Z-Score (-0.54 SD), While Subcutaneous Fat Z-Score Increased From an Initial Negative Value (+0.11 SD) – Indicating a Treatment-Induced Shift Towards a More Balanced Body Fat Distribution With a Marked Decrease in Visceral and Liver Fat.

03

On 22-4-9, Lisata Therapeutics, a clinical-stage pharmaceutical company focused on developing innovative therapies for advanced solid tumors and other serious diseases, announced that the FDA has granted Orphan Drug Designation (ODD) to its leading drug candidate, LSTA1, for the treatment of osteosarcoma, a rare cancer that develops in children, adolescents, and young adults. On 2024-3-21, the company announced that LSTA1 had recently received a Rare Pediatric Disease Designation for osteosarcoma.

Among them, LSTA1 is an investigational drug designed to activate a novel uptake pathway, enabling co-administered or fixed (i.e., covalently bound) anticancer drugs to penetrate solid tumors more effectively. LSTA1 activates this active transport system in a tumor-specific manner, leading to more effective penetration and accumulation of systemically co-administered anticancer drugs within the tumor. LSTA1 also has the potential to alter the tumor microenvironment, making tumors more susceptible to immunotherapy. Lisata and its collaborators have gathered extensive non-clinical data demonstrating enhanced delivery efficiency for a range of existing and emerging anticancer therapies, including chemotherapeutic agents, immunotherapies, and RNA-based treatments. Additionally, LSTA1 has shown favorable safety, tolerability, and activity in clinical trials, enhancing the therapeutic drug delivery effects of the standard of care (SoC) chemotherapy for pancreatic cancer. Lisata is exploring the potential of LSTA1 to enhance multiple treatment modalities for more effective treatment of a variety of solid tumors. LSTA1 has received Orphan Drug Designation (ODD) for pancreatic cancer in the United States and Europe, as well as ODD for glioblastoma multiforme and osteosarcoma in the United States. It has also received Fast Track designation from the FDA for pancreatic cancer and, more recently, Rare Pediatric Disease designation from the FDA for osteosarcoma.

01

Kristi L. Kiick from the University of Delaware published an article titled "Controlled Release of Drugs from Extracellular Matrix-Derived Peptide-Based Nanovesicles through Tailored Noncovalent Interactions" in Biomacromolecules.

The article points out that the author previously reported a type of nanovesicle (ECnVs) composed of elastin-like polypeptide (ELP) and collagen-like peptide (CLP), demonstrating its ability to encapsulate hydrophobic model molecules. ELP consists of pentapeptide repeat sequences (VPGXG)n, where V, P, and G are valine, proline, and glycine, respectively, and X can be any amino acid except proline. ELP is thermosensitive, being soluble below the transition temperature and forming a coacervate phase above the transition temperature. By covalently conjugating ELP with CLP, the phase transition temperature of ELP can be adjusted to near physiological temperature. CLP contains tripeptide repeat sequences (G-X-Y)n, typically ranging from 6 to 10, where X and Y can be proline or hydroxyproline. CLP forms a triple helix at Tm and unfolds into a random coil monomer above Tm. ELP-CLP conjugates can self-assemble into nanoparticles near physiological temperature and exhibit high stability. Unfolded single-chain CLP has a strong tendency to target collagen through efficient and specific triple-helix hybridization.

In the article, the author demonstrated that ECnV can successfully encapsulate and deliver hydrophobic small-molecule drugs while maintaining thermal stability and sustained drug release. High drug loading can be achieved through encapsulation within the ECnV lumen and interactions with CLP. A 2D collagen-binding assay confirmed the collagen-targeting ability of each ECnV, which may have significant implications for future drug delivery and disease treatment using a universal ECnV platform.