George Medicines demonstrates potential of novel, low-dose, triple combination pill to transform management of hypertension in Hot Line Session at ESC Congress 2024
- Results from two Phase III trials testing multi-mechanism, triple combination of existing best-in-class medicines in novel low and ultra-low dose pills
- Combination pill significantly reduced blood pressure and improved control rates vs dual therapy or placebo, with good tolerability and no increase in adverse event withdrawals
- Results also presented from first trial in Africa evaluating a low-dose triple combination pill as initial or early therapy for hypertension, with GMRx2 superior to standard care protocol and achieving over 80% BP control from 1 month to end of follow-up
London, UK 31 August 2024 – George Medicines, a late-stage, biopharmaceutical company addressing significant unmet need in the treatment of cardiometabolic disease, today announced the presentation of results from its two pivotal Phase III trials at a Hot Line session of the European Society of Cardiology (ESC) Annual Meeting in London
The trials tested GMRx2, George Medicines’ novel, multi-mechanism triple combination candidate for the treatment of hypertension (high blood pressure), including initiation of treatment. GMRx2 contains best-in-class medicines, telmisartan, amlodipine and indapamide, in proprietary, triple quarter-dose (ultra-low dose), triple half-dose (low-dose) and triple standard-dose options.
Globally, most people treated for hypertension do not achieve sustained blood pressure (BP) control, primarily due to continued use of low efficacy regimens such as monotherapy. Currently available triple combinations are only available for patients who are still not achieving adequate BP control following treatment with the three separate medicines or two of the components. While trials of low-dose combinations had shown considerable promise for initial and early treatment, these were all with “research-only” formulations which were not available to patients long-term. GMRx2 has been developed to meet this need.
GMRx2 vs dual combinations
In the first Phase III trial, among patients in Australia, Czech Republic, New Zealand, Poland, Sri Lanka, UK and the US, GMRx2, standard- and half-dose forms 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-measured BP change from randomization to week 12. The trial met all primary safety and efficacy endpoints:
- GMRx2 was more effective than dual therapy, significantly reducing both home- and clinic-measured BP and improving BP control rates, with both standard- and half-dose forms.
- The primary outcome was superiority of GMRx2 vs each of the three dual combinations for home systolic blood pressure reduction and each endpoint was met (p<0.0001).
- GMRx2 half-dose achieved 63% clinic BP control <140/90mmHg, 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%).
- Tolerability was good, with no increase in withdrawal from treatment due to adverse events.
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 and, as such, is highly relevant to recent guideline recommendations for lower blood pressure targets.
GMRx2 vs placebo
A second Phase III trial, conducted in Australia, Nigeria, Sri Lanka, UK and the US, compared half- and quarter-doses of GMRx2 against a placebo pill, examining the difference between GMRx2 and placebo in home-measured BP change from randomization to week 4. In that trial GMRx2 significantly improved home- and clinic-measured BP and control rates, in both half- and quarter-doses. Again, tolerability was good, with no increase in withdrawal from treatment due to adverse events.
Presenting at the ESC Congress, Professor Anthony Rodgers, Chief Medical Officer of George Medicines and Professorial Fellow at The George Institute for Global Health, said: “The clinical and public health significance of these findings is considerable, given the continuing global disease burden of hypertension. Control rates are suboptimal in all countries, even where access and affordability are not major factors, principally due to continued use of low-efficacy regimens. With evidence increasingly showing the value of lower blood pressure targets, the potential of an effective, low-dose, triple combination with a good safety profile for the early treatment of hypertension should not be underestimated.”
Chair of the trials’ 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, said: "These clinical trial results confirm GMRx2 as a novel antihypertensive therapy that could substantially improve hypertension control rates, worldwide.”
GMRx2 for hypertension in Africa
The potential of GMRx2 in Africa was also demonstrated at the ESC Congress with results shared from a recently completed clinical trial in hospital-based family medicine clinics in Nigeria, the first trial to evaluate a low-dose triple combination pill as initial or early therapy for hypertension in Africa. Led by Professor Dike Ojji at University of Abuja and Dr. Abdul Salam from the George Institute India, the VERONICA (deliVERy of Optimal blood pressure coNtrol in afrICA) trial, recruited black African adults with uncontrolled hypertension, who were either untreated or already receiving a single BP-lowering drug. The trial compared GMRx2-based treatment protocol with existing, standard care protocol for six months.
The trial’s primary effectiveness outcome was home-measured BP from randomization to month 6 and the primary safety outcome was discontinuation of trial treatment due to an adverse event. The trial demonstrated:
- Clinically and statistically significant improvements in efficacy with GMRx2 – reductions in home- and clinic-measured BP from randomization to month 6.
- Over 80% BP control achieved at month 1 and maintained throughout follow-up – control rates were superior at all timepoints, even though by 6 months 70% BP control had been achieved in the comparator group, which was a high standard of care and at least as good as that seen in most high-income settings.
- None of the patients withdrew from the trial due to adverse events; tolerability was good with only hypokalaemia observed, mostly mild.
The trial was funded by the National Health and Medical Research Council (NHMRC) of Australia, supported by The George Institute for Global Health and medicine was supplied by George Medicines.
Mark Mallon, Chief Executive Officer of George Medicines, said: “These comprehensive data underscore the science behind GMRx2 and reinforce its potential to transform the management of hypertension. GMRx2’s multi-mechanism approach delivers the synergistic efficacy benefits of a triple therapy while maintaining tolerability, and in a single pill that can be expected to improve patient adherence. Subject to its review by regulators, GMRx2 would be the first medicine approved for the initial treatment of hypertension for over a decade, and could deliver profound results for patients globally, including in low- and middle-income countries whose populations carry a significant hypertension burden.”
Earlier this month, 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’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 hypertension (high blood pressure)
Globally, more than one billion adults have hypertension1.
In the US, nearly half of adults have hypertension (120 million) and only around 1 in 4 of those have their hypertension under control (27 million), either because they are not being treated or their treatment is suboptimal2.
In the UK, around 1 in 3 adults has hypertension. Half of those with high blood pressure are not diagnosed or receiving treatment. In England alone, there are more than five million people that are undiagnosed3.
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 guidelines4 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
- World Health Organization Hypertension factsheet https://www.who.int/news-room/fact-sheets/detail/hypertension
- Million Hearts® https://millionhearts.hhs.gov/data-reports/hypertension-prevalence.html#:~:text=Nearly%20half%20of%20adults%20have,5%20adults%20(25.0%20million)
- Blood Pressure UK https://www.bloodpressureuk.org/news/media-centre/blood-pressure-facts-and-figures/#:~:text=Around%20one%20in%20three%20adults,that%20are%20undiagnosed%5B6%5D
- 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;; 2018 ESC/ESH Clinical Practice Guidelines for the Management of Arterial Hypertension https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines/Arterial-Hypertension-Management-of
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