First Licensed Equine SGLT2i Validated but Small Data and Lipid Risk Temper Upside

CVMP Adopts Positive Opinions for Multiple Veterinary Medicinal Products

The Committee for Veterinary Medicinal Products (CVMP) adopted a positive opinion for a marketing authorisation for Scovella (velagliflozin), intended to reduce hyperinsulinaemia and the associated risk of laminitis in horses with Equine Metabolic Syndrome unresponsive to husbandry and exercise changes. Scovella marks the first veterinary medicinal product recommended under the limited market regulatory framework since Regulation (EU) 2019/6 came into effect in 2022, allowing authorisation based on customised documentation and a favourable benefit-risk assessment for limited markets.

• Scovella (velagliflozin) received a positive opinion for marketing authorisation, notably being the first veterinary medicinal product recommended under the limited market regulatory framework. This framework, active since Regulation (EU) 2019/6 in 2022, enables tailored authorisation requirements and a favourable benefit-risk assessment for products targeting limited markets, addressing unmet needs in specific animal populations.
• The CVMP also issued a positive opinion for Credelio Quattro (lotilaner/moxidectin/pyrantel/praziquantel), a combination product for dogs. This veterinary medicine is indicated for the treatment of mixed external and internal parasitic infestations, specifically targeting ectoparasites, cestodes, and nematodes, providing a comprehensive solution for canine health when multiple parasitic threats are present.
• Laverdia (verdinexor) received a positive opinion for marketing authorisation, aimed at increasing the time to progression in dogs diagnosed with stage II, III, and IV lymphoma. Classified as a minor use, minor species/limited market product, Laverdia offers a crucial therapeutic option for managing advanced lymphoma in a home setting, addressing a significant need in veterinary oncology.
• The Committee adopted the 'Fifth joint inter-agency report on integrated analysis of antimicrobial agent consumption and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals in the EU/EEA' (JIACRA V). This report introduces a stronger One Health approach, incorporating environmental data and analysing post-COVID trends, providing long-term evidence that reduced antimicrobial use correlates with improved bacterial susceptibility.

Velagliflozin's Broader Pipeline Beyond Equine Metabolic Syndrome

Velagliflozin, a once-daily, liquid, oral SGLT2 inhibitor, is investigated as sole therapy for feline diabetes mellitus in naïve and previously insulin-treated diabetic cats. The SENSATION study evaluated safety and effectiveness in diabetic cats, with an additional case report describing diabetic remission in a newly diagnosed diabetic cat treated with velagliflozin.

The Unmet Needs in Managing Equine Metabolic Syndrome

Current management of equine metabolic syndrome relies on dietary restriction, increased exercise and adequate treatment of concurrent pituitary pars intermedia dysfunction, with drugs such as metformin, levothyroxine and sodium-glucose cotransporter-2 inhibitors used off-label. Despite these measures, refractory hyperinsulinaemia, lack of licensed therapies and practical constraints on sustained weight loss leave a substantial residual risk of laminitis.

• Refractory disease despite multimodal therapy: Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) required escalation to canagliflozin, and medical treatment with levothyroxine or metformin may be indicated in animals that do not respond to conservative dietary management.

• No licensed veterinary therapy for insulin dysregulation: There are no licenced veterinary drugs available for treating ID and preventing insulin-associated laminitis in horses, and the doses used for canagliflozin, ertugliflozin and velagliflozin are largely extrapolated from human studies with limited consideration of species-specific variations.

• Translational and safety gaps for SGLT2 inhibitors: Most horses with ID remain hyperinsulinaemic but normoglycaemic such that increased urinary loss of glucose may not explain the beneficial effects of these drugs, and further study of the potential deleterious effects of treatment-associated hypertriglyceridaemia is required together with the effect of SGLT2i therapy on circulating concentrations of adipokines in horses. All horses experienced a transient increase in serum triglyceride concentration during velagliflozin treatment, and further controlled trials to investigate canagliflozin pharmacokinetics, pharmacodynamics, efficacy, and safety are needed.

• Limited effectiveness and compliance with diet and exercise: Calorie restriction and increased exercise are the mainstays of treatment but there is potential for poor owner compliance, and a dynamic feeding system that induced sustained low-intensity exercise promoted weight loss in ponies but this exercise may not be sufficient to substantially improve SI.

• Nutritional trade-offs and monitoring burden: Weight reduction occurs normally on a diet of late-cut hay, a hay-straw mixture or grass seed straw at 1-1.2% of ideal body weight, yet this roughage allowance does not satisfy the need of horses to chew, for which it requires at least 1.5% of ideal body weight, which may lead to behavioural issues, such as allophagia and aggression, and in extreme cases, stereotypic behaviour. Weight loss should be 0.5-1% of body weight per week, while at a higher rate there is a potential risk of hyperlipemia, and hay soaking leached nutrients, reduced DM and DE provision and was associated with accelerated weight losses over those expected had fresh-hay been fed to the same level.

• High recurrence and under-recognition of laminitis: The recurrence rate for endocrinopathic laminitis was 34.1%, with risk increasing with basal, fasted serum insulin concentration beyond the normal range (0-20 μIU/mL) to over the threshold for normal (up to approximately 45 μIU/mL), while owners reported laminitis in 37% of animals with PPID yet 76% were laminitic based on study criteria.

Understanding Current Standard of Care for Equine Metabolic Syndrome

Management of equine metabolic syndrome (EMS) is centered on dietary control as the primary approach, as there are no licenced veterinary drugs available for treating insulin dysregulation (ID) and preventing insulin-associated laminitis in horses. Dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinaemia, with strict control of dietary nonstructural carbohydrates (NSCs), elimination of grains and sweet feeds from the ration and restricted access to pastures that may be rich in NSCs. Calorie restriction to promote weight loss improves insulin sensitivity in obese animals, including feeding grass hay restricted to 1.25% of body mass as daily dry matter intake and soaked in cold water prior to feeding, or late-cut hay, hay-straw mixture or grass seed straw at 1-1.2% of ideal body weight. Soaking hay resulted in a significant reduction in non-structural carbohydrates (38%, P = 0.01) and digestible energy (6.78%, P = 0.01), and following 6 weeks of dietary restriction horses lost an average of 6.8% body mass with improved insulin sensitivity as determined by the total insulin response during the combined glucose insulin test.

Increased exercise and restricted pasture exposure are core aspects of therapy alongside diet, with exercise when possible and adequate treatment of pituitary pars intermedia dysfunction (PPID) maintained as essential components. A diet and exercise programme tailored to the needs of the individual animal and implemented by the owner results in weight loss accompanied by improvements in insulin sensitivity, and regular exercise, such as a daily 30-minute speedy trot, improves insulin sensitivity. For pasture-based horses, reducing caloric intake by using grazing muzzles and increasing caloric expenditure through exercise limits intake of high-quality pasture grass, with peak insulin greater in control (45.59±21.07µIU/mL) than muzzled (24.31±14.37µIU/mL) horses (p < 0.001) during a 10h summer grazing period. Diagnosis and management of hyperinsulinaemia is recommended to reduce the risk of laminitis, as insulin dysregulation is the most important risk factor for development of laminitis and higher basal insulin concentrations were associated with more severe lameness.

Pharmacologic therapy may apply when conservative management is insufficient, with reasonable justification for use of drugs such as levothyroxine and metformin, and medical treatment with levothyroxine or metformin may be indicated in animals that do not respond to conservative dietary management. In horses with concurrent PPID, treatment uses the dopamine agonist pergolide, which improves most clinical signs associated with PPID and lowers basal adrenocorticotropic hormone (ACTH) concentrations, but measures of insulin dysregulation are not altered in most cases and pergolide does not affect insulin sensitivity. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) including canagliflozin, ertugliflozin and velagliflozin have been reported to aid management of equine ID, with once daily administration of canagliflozin correcting hyperglycemia and reducing insulin to normal or near normal levels with resolution of laminitis pain in refractory cases. Canagliflozin should be reserved for refractory cases, with renal function assessed by serum creatinine and blood urea nitrogen concentrations and diet control, exercise and PPID treatment maintained, while the synthetic GLP-1 analog exenatide resulted in a postprandial decrease of 20% in area under the curve of plasma insulin through increased whole-body insulin sensitivity and may have therapeutic potential for ID in horses.