A novel low-dose, triple, single-pill combination therapy demonstrated significant efficacy in blood pressure reduction and improved control rates in two international trials presented at the European Society of Cardiology Congress 2024.

The combination, known as GMRx2, contained telmisartan, amlodipine, and indapamide, and was tested in various dose strengths against placebo and dual therapies.

Among the key findings:

• GMRx2 at one-quarter and one-half doses achieved significant blood pressure (BP) reductions compared with placebo.
• The triple combination therapy showed superior efficacy compared with dual therapies.
• BP control rates (< 140/90 mmHg) reached 70% with the one-half dose of GMRx2.
• Treatment demonstrated similar tolerability to placebo and dual therapies.

In the international, double-blind placebo-controlled trial, researchers recruited 295 adult patients with hypertension receiving zero to one BP-lowering drugs. After a 2-week placebo run-in period, the patients with home systolic BP 130 to 154 mmHg were randomly assigned 2:2:1 to receive a one-quarter dose of GMRx2 (telmisartan 10 mg, amlodipine 1.25 mg, and indapamide 0.625 mg), one-half dose of GMRx2 (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), or placebo.

The results showed:

• Mean baseline clinic BP = 138/86 mmHg
• Placebo-corrected difference in home systolic BP at week 4: one-quarter dose of GMRx2 quarter dose = −7.3 mmHg (95% confidence interval [CI] = −4.5 to −10.8), one-half dose of GMRx2 = −8.2 mmHg (95% CI = −5.2 to −11.3)
• Clinic BP control (< 140/90 mmHg) rates: placebo = 37%, one-quarter dose of GMRx2 = 65% (P < .001 vs placebo), one-half dose of GMRx2 = 70% (P < .001 vs placebo)
• Treatment withdrawal due to adverse events: placebo = 1.6%, one-quarter dose of GMRx2 = 0%, one-half dose of GMRx2 = 5.1%.

In the double-blind active-controlled trial, researchers recruited 1,385 adult patients with hypertension receiving 0 to 3 BP-lowering drugs. Screening systolic BP ranged from 140 to 179 mmHg (with no drugs) to 110 to 150 mmHg (with 3 drugs). After a 4-week active run-in period with a one-half dose of GMRx2, the patients were randomly assigned 2:1:1:1 to receive a half dose of GMRx2, telmisartan 20 mg/amlodipine 2.5 mg, telmisartan 20 mg/indapamide 1.25 mg, or amlodipine 2.5 mg/indapamide 1.25 mg.

At week 6, the doses were doubled in all groups unless contraindicated.

The results demonstrated:

• Mean baseline clinic BP = 142/85 mmHg (screening), 133/81 mmHg (post run-in)
• Home BP reductions at week 12 (GMRx2 vs dual therapies): vs telmisartan/indapamide = 2.5/2.1 mmHg (P < .0001), vs telmisartan/amlodipine = 5.4/3.4 mmHg (P < .0001), vs amlodipine/indapamide = 4.4/3.6 mmHg (P < .0001)
• Clinic BP control (< 140/90 mmHg) rates at week 12: GMRx2 = 74%, telmisartan/indapamide = 61% (P ≤ .0001 vs GMRx2), telmisartan/amlodipine = 61% (P ≤ .0001 vs GMRx2), amlodipine/indapamide = 53% (P ≤ .0001 vs GMRx2)
• Treatment withdrawal due to adverse events: GMRx2 = 2.0%, telmisartan/indapamide = 1.4%, telmisartan/amlodipine = 1.1%, amlodipine/indapamide = 1.4%.

The active-controlled trial recruited participants from Australia, Czech Republic, New Zealand, Poland, Sri Lanka, United Kingdom, and the United States. GMRx2 was available in three dose strengths: triple quarter doses = telmisartan 10 mg, amlodipine 1.25 mg, and indapamide 0.625 mg; triple half doses = telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg; triple standard doses = telmisartan 40 mg, amlodipine 5 mg, and indapamide 2.5 mg. 

In the placebo-controlled trial, the primary efficacy outcome was the mean change in home systolic BP from baseline to week 4. The primary safety outcome in the placebo-controlled trial was treatment withdrawal due to an adverse event. In the active-controlled trial, the primary efficacy outcome was mean change in home systolic BP from baseline to week 12.

The trials addressed the global issue of inadequate BP control in patients treated for hypertension, which was primarily caused by continued use of low-efficacy regimens including monotherapy. The researchers developed GMRx2 as a single-pill combination of different low-dose drugs, aiming to improve hypertension management through additive benefits, rapid action, and a low risk of adverse events.

Both trials were funded by George Medicines Pty Ltd. TGI has patent applications for low-dose combination hypertension products, with Anthony Rodgers, Professor at the George Institute for Global Health at the University of New South Wales in Australia, as an inventor. George Medicines Pty Ltd, a TGI subsidiary, holds the patent license. Dr. Rodgers is part-time seconded to George Medicines but has no financial interest in the patents or company.