Phase III trial results of novel triple combination pill for hypertension published in The Lancet

Phase III trial results of novel triple combination pill for hypertension published in The Lancet

• Novel combination pill significantly reduced blood pressure and improved control rates vs dual therapy, with good tolerability and no increase in adverse event related withdrawals
• Triple combination approach aligns with latest European Society of Cardiology hypertension guidelines recommending increased use of combination therapies
• Subject to regulatory review, following New Drug Application (NDA) filed with FDA in August, GMRx2 would be the first triple combination approved for initial treatment of hypertension

London, UK, 18 October 2024 – George Medicines, a late-stage biopharmaceutical company focused on addressing significant unmet needs in cardiometabolic disease treatment, today announced that The Lancet has published results from its pivotal Phase III clinical trial of GMRx2.

A proprietary combination of three best-in-class medicines, telmisartan, amlodipine and indapamide, developed in an ultra-low dose (triple quarter-dose), low-dose (triple half-dose), and triple standard-dose options, GMRx2 was compared with dual combinations, for the treatment of hypertension (high blood pressure), including initiation of treatment. The triple combination’s multi-mechanism approach is designed to deliver optimal efficacy and safety while promoting patient adherence.

The research, “Efficacy and safety of a novel low-dose triple single-pill combination of telmisartan, amlodipine and indapamide, compared with dual combinations for treatment of hypertension: a randomised, double-blind, active-controlled, international clinical trial”, is published in the 19 October issue of The Lancet.

The international trial, conducted in seven countries, met all primary efficacy and safety endpoints:

• GMRx2 was more effective than each dual therapy, significantly reducing both home- and clinic-measured blood pressure (BP) and improving BP control rates, with both standard- and half-dose forms.
• GMRx2 half-dose achieved 63% clinic BP control <140/90 mmHg, which rose to 74% at the end of follow-up on GMRx2 standard-dose – superior to all three dual combinations at standard-dose (53-61%).
• Assessed against more stringent BP control rates of <130/80 mmHg, GMRx2 standard dose achieved 56% control rates, again clinically and statistically superior to all three dual combinations (33-44%).
• Tolerability was good, with no increase in withdrawal from treatment due to adverse events.

This treatment approach aligns with recently updated European Society of Cardiology (ESC) guidelines for hypertension management¹, which recommend lower blood pressure levels to begin treatment among those at raised risk and greater use of combination therapy, starting off with dual low-dose followed by a triple low -dose therapy.

Chair of the trial’s steering committee, Dr. Paul Whelton, Show Chwan Chair of Global Public Health at Tulane University, New Orleans, Louisiana, and President of the World Hypertension League, commented: “This trial, conducted across seven countries and diverse populations, demonstrates that GMRx2 provides significantly better blood pressure control compared to dual combinations, while maintaining an excellent safety profile. The findings are particularly noteworthy as they show efficacy at lower blood pressure levels, aligning with the latest guideline recommendations. This new single-pill combination has the potential to address the critical need for more effective and tolerable treatment options to achieve and maintain blood pressure control in the many patients who remain uncontrolled on current therapies.”

Dr. Anthony Rodgers, Chief Medical Officer of George Medicines, and Professorial Fellow at The George Institute for Global Health, said: “These findings, now published in The Lancet, provide robust evidence for the potential of GMRx2 to transform hypertension management. The superior efficacy of this triple combination therapy compared to dual combinations, coupled with its good tolerability, addresses key challenges in current hypertension treatment approaches and directly supports recent guideline recommendations. Subject to regulatory approval, we believe GMRx2 could play a crucial role in addressing the global burden of hypertension and improving patient outcomes.”

These results, along with data from other recent trials, including the VERONICA trial in Nigeria, funded by the National Health and Medical Research Council (NHMRC) of Australia, supported by The George Institute for Global Health and recently published in JAMA, and a placebo-controlled Phase III study recently published in the Journal of the American College of Cardiology, provide a comprehensive body of evidence supporting the efficacy and safety of GMRx2 across various patient populations and dosing regimens.

In August 2024 George Medicines announced its submission to the US Food and Drug Administration (FDA) of a New Drug Application (NDA) for GMRx2. Data from GMRx2’s clinical development program will support additional global regulatory filings.

George Medicines is an independent spin-out company from The George Institute for Global Health, one of the world’s leading medical research institutes with a focus on addressing global health inequity. The Company is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm. The Company’s GMRx2 development program built on earlier research by The George Institute, including the 700-patient TRIUMPH trial undertaken in Sri Lanka in 2016/17, which found that among patients with mild to moderate hypertension, treatment with a low-dose triple combination pill led to an increased proportion of patients achieving their target blood pressure goal versus usual care.

Ends

About the clinical trial
A Phase III trial among 1,385 patients in Australia, Czech Republic, New Zealand, Poland, Sri Lanka, UK and the US, standard- and half-dose forms of GMRx2 were tested against dual combinations of its component drugs. The trial’s primary efficacy outcome was the difference between GMRx2 and its comparators in home blood pressure change from randomization to week 12.

The head-to-head trial provides the first large scale comparison of a low- and standard-dose triple combination pill and its dual combinations at the same doses. It assessed the safety and efficacy of the triple combination among patients with starting blood pressure levels that were considerably lower than those in previous trials.

About hypertension (high blood pressure)
Globally, more than one billion adults have hypertension².

Many diagnosed patients aren’t achieving sufficient blood pressure control because they are on inadequate therapy, aren’t receiving the right combination of medicines at the right doses or aren’t taking their treatment as prescribed or continuing their treatment in the long term.

The major, globally recognized treatment guidelines³ recommend the use of fixed dose combination therapy for most patients with hypertension, including for first-line treatment and yet, in practice, newly diagnosed patients will often still be prescribed monotherapy treatment. This is despite a broad evidence base indicating that, individually, blood pressure medicines are only modestly effective at reducing blood pressure, even at high doses, and most patients will require two or more medicines to achieve control.

As dosage of hypertension drugs is increased, so too are side effects, which can preclude the use of high doses for many patients. These side effect challenges, alongside the management of multiple hypertension medicines being taken together with treatments for other conditions, can significantly impact treatment compliance and adherence, including failure to take medications as prescribed and to persist on long-term therapy.

About George Medicines
George Medicines is a late-stage biopharmaceutical company addressing significant unmet need in the treatment of cardiometabolic diseases with innovative combinations of best-in-class existing treatments, designed for optimal efficacy and safety.

Combining best-in-class molecules from existing medicines in novel low-dose formulations, George Medicines is developing innovative and proprietary treatments to be more efficacious, safer and accessible than currently available treatment options. These multi-mechanism, single-pill combinations offer the potential to bring significant improvements in clinical outcomes and therapy adherence in patients with cardiometabolic disorders, including hypertension and diabetes, each of which remain the leading causes of premature death and disability worldwide.

The Company’s lead candidate, GMRx2, has completed a Phase III development program for the treatment of hypertension, including first-line therapy, and a global trial focused on the prevention of recurrent intracerebral hemorrhage (the most severe type of stroke) is underway.

George Medicines is an independent spin-out company from The George Institute for Global Health, one of the world’s leading medical research institutes with a focus on addressing global health inequity. The Company is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm. For more information, please visit www.george-medicines.com.

References

1. 2024 ESC Guidelines for the management of elevated blood pressure and hypertension
2. World Health Organization Hypertension factsheet https://www.who.int/news-room/fact-sheets/detail/hypertension
3. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines https://www.ahajournals.org/doi/10.1161/HYP.0000000000000065; WHO Guideline for the pharmacological treatment of hypertension in adults https://iris.who.int/bitstream/handle/10665/344424/9789240033986-eng.pdf; 2024 ESC Guidelines for the management of elevated blood pressure and hypertension

Media contacts

ICR Consilium
David Daley, Lindsey Neville, Isabelle Abdou
[email protected]; Tel: +44 (0) 203 709 5700