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The findings may inform treatment strategies focused on using tools for estimating insulin resistance and selecting insulin-sensitizing drugs which may improve exercise capacity and cardiac function.

In heart failure with preserved ejection fraction insulin resistance and obesity are prevalent and are associated with adverse cardiovascular (CV) outcomes. Insulin resistance measurement is difficult outside of research settings, and there is no information on its correlation to parameters of myocardial dysfunction and functional status.

To fill this knowledge gap, Allison G. Hays, University School of Medicine, Baltimore, MD, USA, and colleagues aimed to assess the role of estimated glucose disposal rate (eGDR), an easily calculated metric using commonly available clinical variables that reflects insulin resistance, in a well-characterized cohort of HFpEF patients.

They tested the hypothesis that increased insulin resistance (measured by reduced eGDR) is associated with abnormalities in cardiac function and structure in patients with HFpEF.

The study included 92 HFpEF patients with New York Heart Association class II to IV symptoms. The mean age of the participants was 65 years, 64 % were women, and 95 % had hypertension. Mean (SD) BMI was 39 (9.6) kg/m2, glycated haemoglobin 6.7 (1.6) %, and eGDR 3.3 (2.6) mg × kg−1 min−1. They underwent 2D echocardiography, clinical assessment, and a 6-minute walk (6 MW) test. Insulin resistance was defined by the estimated glucose disposal rate. Lower eGDR indicates increased insulin resistance (unfavourable).

Myocardial function and structure were assessed by average E/e’ ratio, left ventricular (LV) mass, left atrial volume, right ventricular systolic pressure, LV longitudinal strain (LVLS), LV ejection fraction, and tricuspid annular plane systolic excursion. Association were evaluated between eGDR and adverse myocardial function in unadjusted and multivariable-adjusted analyses using analysis of variance testing and multivariable linear regression.

The study led to the following findings:

• Increased insulin resistance was associated with worse LVLS in a graded fashion [mean −13.8 %, −14.4 %, −17.5 % for first, second, and third eGDR tertiles, respectively]. This association persisted after multivariable adjustment.
• There was also a significant association between worse insulin resistance and decreased 6 MW distance on univariate analysis, but not on multivariable-adjusted analysis.

“In a well-characterized cohort of HFpEF patients, our findings showed a significant relationship between eGDR and LVLS, suggesting that insulin resistance is associated with CV pathology that contributes to HFpEF pathophysiology, independent of common covariates implicated in HFpEF,” the researchers wrote.

Reference:

Gudenkauf, B., Shaya, G., Mukherjee, M., Michos, E. D., Madrazo, J., Mathews, L., Shah, S. J., Sharma, K., & Hays, A. G. (2024). Insulin resistance is associated with subclinical myocardial dysfunction and reduced functional capacity in heart failure with preserved ejection fraction. Journal of Cardiology, 83(2), 100-104. https://doi.org/10.1016/j.jjcc.2023.06.008

The US Food and Drug Administration has approved travoprost intracameral implant for treatment of ocular hypertension and glaucoma.

The implant iDose TR developed by Glaukos is designed to provide long-duration treatment for the full range of glaucoma disease severity.

iDose TR is a first-of-its-kind, long-duration, intracameral procedural pharmaceutical therapy designed to continuously deliver 24/7 therapeutic levels of a proprietary formulation of travoprost inside the eye for extended periods of time. iDose TR is intended to improve the standard of care by addressing the ubiquitous patient non-compliance issues and chronic side effects associated with topical glaucoma medications.

“The FDA approval of iDose TR represents a significant milestone for Glaukos following an extensive pioneering journey since the inception of the original idea nearly 15 years ago. Today’s approval ushers in a new era of interventional glaucoma therapy by enabling a more proactive and reliable approach for patients in need,” said Thomas Burns, Glaukos chairman and chief executive officer. “We believe iDose TR can be a transformative, novel technology able to fundamentally improve the treatment paradigm for patients with open-angle glaucoma or ocular hypertension. We are grateful to the clinical investigators and study participants in the clinical trials for their instrumental roles in helping us reach this important advancement for glaucoma patient care. At Glaukos, we are relentlessly focused on delivering novel therapies for chronic eye diseases and now iDoseTR has the potential to redefine the standard of care for patients in the U.S. affected by open-angle glaucoma and ocular hypertension.”

“With the next generation of procedural pharmaceutical solutions for glaucoma such as iDose TR, we now have a new tool that will confront the standard legacy practice of relying on topical drops, which are known to cause uncomfortable side effects and present a myriad of challenges such as treatment adherence, complex dosing regimens, and difficulty with self-administration,” said John Berdahl, MD, clinician and researcher at Vance Thompson Vision. “The clinical data suggest that iDoseTR is not only effective with a favorable safety profile, but it has potential to relieve patients from the burdens of prescription eye drops for an extended period of time. I look forward to adding this novel therapy into my treatment toolbox for the benefit of my patients.”

The FDA approval is based on results from two prospective, randomized, multicenter, double-masked, Phase 3 pivotal trials (GC-010 and GC-012) designed to compare the safety and efficacy of a single administration of one of two iDose TR models with different travoprost release rates (referred to as the fast- and slow-release iDose TR models, respectively) to topical timolol ophthalmic solution, 0.5% BID (twice a day), in reducing IOP in subjects with open-angle glaucoma or ocular hypertension. In total, the Phase 3 trials randomized 1,150 subjects across 89 clinical sites. The FDA approval and Phase 3 data referenced below is for the slow-release iDose TR model, consistent with the company’s NDA submission and commercialization plans.

Both Phase 3 trials successfully achieved the pre-specified primary efficacy endpoints through 3 months and demonstrated a favorable tolerability and safety profile through 12 months. IOP reductions from baseline over the first 3 months were 6.6-8.4 mmHg in the iDose TR arm, versus 6.5-7.7 mmHg in the timolol control arm (mmHg range represents IOP reduction means across the six U.S. FDA pre-specified timepoints of 8 a.m. and 10 a.m. at Day 10, Week 6 and Month 3). Based on these outcomes, the FDA concluded in the prescribing information that iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. The FDA also noted that subsequently iDose TR did not demonstrate non-inferiority over the next 9 months.

At 12 months, 81% of iDose TR subjects were completely free of IOP-lowering topical medications across both trials. In both trials, iDose TR demonstrated excellent tolerability and subject retention with 98% of iDose TR subjects continuing in the trial at 12 months, versus 95% of timolol control subjects. In controlled studies, the most common ocular adverse reactions reported in 2% to 6% of iDose TR patients were increases in intraocular pressure, iritis, dry eye, and visual field defects, most of which were mild and transient in nature.

iDose TR is also supported by positive results from a Phase 2b clinical trial, which were recently highlighted in a peer-reviewed publication in Drugs ). The study authors concluded, “The travoprost intraocular implant demonstrated robust IOP-lowering and substantially reduced topical IOP-lowering medication burden for up to 36 months following a single administration, while maintaining a favorable safety profile.”

Glaukos intends to commence initial commercial launch activities for iDose TR in the latter part of the first quarter of 2024. Glaukos has established a wholesale acquisition cost for iDose TR of $13,950, per dose (or implant).

Alongside the iDose TR approval announcement, Glaukos is proud to introduce the iDose Your Dose Initiative. For every iDoseTR sold, Glaukos pledges to make available an equal number of iDoseTR units for qualifying charitable donation requests in the U.S. and around the globe for recipients that satisfy independent eligibility requirements.