Cardiovascular Outcomes Remain Primary Focus of Drug Trials

Brief news features on recently released FDA approvals and preliminary clinical trials results for the weight loss drug locaserin, a diabetes combination therapy, and inhaled insulin.

Belviq Appears to Stand Up to Clinical Rigor for CVD/Diabetes/Obesity

Favorable preliminary findings have been reported out of the randomized, double-blind, placebo-controlled, parallel-group phase 3b/4 Cardiovascular Outcomes Trial in collaboration with the Thrombolysis in Myocardial Infarction study (CAMILLIA-TIMI 61) regarding the safety and efficacy of lorcaserin hydrochloride (Beliviq) as a metabolic adjuvant to a weight management plan that includes a calorie-controlled diet and increased physical activity,1 according to the company, Eisai.

For people with risk of HD, Diabetes, and Obesity, Locaserin Offers Benefits. Photo: 123RF.

Not only did lorcaserin show no adverse impact on cardiovascular events, but there was also a reduction in new onset of cases of type 2 diabetes in individuals who began the study with no prior history of disease, as well as fewer cardiovascular events.1

Meeting the primary endpoint for safety, this is the first weight loss medication for which there is clinical trial data to support the long-term use of Lorcaserin with no increase in the incidence of major adverse cardiovascular (CVD) events (MACE+) including death, non-fatal myocardial infarction, and non-fatal stroke, hospitalization for unstable angina, heart failure or coronary revascularization.

Given the positive safety profile, the trial was extended to evaluate the effects of lorcaserin on MACE, demonstrating significant improvement in secondary endpoints such as lipid levels, serum glucose, renal function, and blood pressure as well as a rate of onset to type 2 diabetes in participants to enter the study without diabetes.

Furthermore, in a subgroup analysis, lorcaserin showed improvements in long-term maintenance of lost weight as compared with placebo for people with T2D and obstructive sleep apnea.

Initiated to assess its the safety and efficacy in individuals with existing CVD or related cardiovascular risk factors or type 2 diabetes who were diagnosed with overweight or obesity, who were recruited from more than 400 institutions in the United States and eight other countries, making this is the largest ongoing post-marketing cardiovascular outcomes trial to date of any anti-obesity treatment.

Belviq was approved by the Food and Drug Administration for adjuvant use with a low-calorie diet and physical activity in adults struggling with chronic obesity in 2012 and became available for use in June 2013. 

Tentative ANDA Status for Combination Therapy: Alogliptin and Metformin

Tentative ANDA Status for Combination Therapy: Alogliptin and Metformin

The Food & Drug Administration granted tentative approval for an Abbreviated New Drug Application (ANDA) for Asenapine sublingual tablets—a combination of alogliptin and metformin hydrochloride tablets (12.5 mg/500 mg and 12.5 mg/1000 mg), 3 according to Alembic Pharmaceuticals Limited.

In evaluating the submission, the Office of Bioequivalence determined that Asenapine demonstrated therapeutic equivalence to the reference listed drug, Saphris sublingual tablets at 5 mg and 10 mg (Forest Laboratories, LLC).3

Final approval was withheld due to a potential issue with patent infringement, and the need for the manufacturer to submit a Risk Evaluation and Mitigation Strategy. Once these matters are provided, Alembic Pharmaceuticals may submit a request for final approval.

The combined alogliptin and metformin tablets hold an indication as adjunctive therapy to improve glycemic control in people with type 2 diabetes when treatment with diet and physical activity are deemed insufficient.

Positive Clinical Data on Inhaled Insulin (Afrezza) Reported  

Results of the STAT study,4 the first of a series of trials of patients with type 1 diabetes (T1D) demonstrated favorable results for serum glucose time-in-range and postprandial excursions with Technosphere insulin (Afrezza, MannKind), was published online in Diabetes Technology & Therapeutics.  

This pilot trial of 60 patients was initiated to assess the difference, if any, of serum glucose time-in-range (70–180 mg/dL) and postprandial glucose excursions of 1–4 hours, for inhaled insulin, Afrezza, in patients using a continuous glucose monitor (CGM) in comparison to insulin aspart delivered by multiple injections.4

This was the first randomized, controlled study to assess the efficacy of diabetes management outcomes in individuals with type 1 diabetes; the trials were conducted by a research team from the Barbara Davis Center for Diabetes at the University of Colorado School of Medicine in Aurora.

The research was a collaborative multicenter clinical trial involving several other investigators around the country, said Halis Kaan Akturk, MD, assistant professor of medicine and pediatrics at the University of Colorado Denver, and principal investigator of the STAT Trial in a press release.

Primary endpoints of the STAT trial4 included:

  • 24-hour glucose time-in-range (TIR) 
  • Postprandial glucose excursions (PPGE), defined as the peak increase in glucose in the 1- to 4-hour post-meal period

When compared to the current standard of care protocol for mealtime (bolus) insulin, the per-protocol use of Technosphere insulin (TI) delivered in supplemental doses at one and/or two hours after meals, on average, resulted in significant findings for the following outcomes:4

  • Increases in glucose time-in-range of about 2 hours a day 
  • Reduction of time-in-hyperglycemia (> 180 mg/dL) 
  • Decline in postprandial glucose up to 4 hours post-meal 
  • Reduction in serum glucose (within 60 minutes of TI dose)
  • Fewer hypoglycemia episodes (> 60 mg/dL); average TI-treated patient spent ~ 3 minutes/day with blood glucose values less than 50 mg/dL versus approximately12 minutes per day for those receiving aspart.

The findings support the distinctive time-action profile of inhaled insulin by demonstrating the potential benefit of this form of insulin delivery for optimal mealtime glucose control, according to the researchers. Specifically, individuals with type 1 diabetes treated with Technosphere insulin experienced lower serum glucose levels even one hour post-meal.4

As well, a supplemental dose of Technosphere insulin provided additional improvement in glucose time-in-range measured after meals in individuals using CGM as compared with the current standard of care for rapid-acting insulin analogs, Dr. Akturk stated.

Funding for this study was provided by MannKind Corporation, manufacturers of Afrezza.

Results of Clinical Trials Anticipated

Findings from a phase 3 study of dasiglucagon to treat severe hypoglycemia in diabetes are anticipated soon, according to Zealand Pharma.

Phase 3 data on Vascepa to treat high triglycerides with mixed dyslipidemia, should be forthcoming, said Amarin Corporation.

 

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