Once approved, the new single pill combination (TWYNSTA®) will provide patients and prescribers with a highly effective combination of telmisartan, an angiotensin receptor blocker (ARB), and amlodipine, a calcium-channel blocker (CCB), for the treatment of hypertension. It will reduce blood pressure effectively and safely in a broad range of patient groups including those with mild, moderate and severe hypertension as well as hypertensive patients at high cardiovascular risk, such as those with diabetes or metabolic syndrome.(1-8)
"We are pleased that, following a final decision from the European Medicines Agency, TWYNSTA® will provide physicians with a valuable new treatment option for hypertensive patients," commented Professor Klaus Dugi, Corporate Senior Vice President Medicine, Boehringer Ingelheim. "The long duration of action of both components of TWYNSTA® make it a unique and very meaningful option in the treatment of hypertension where blood pressure control is not achieved with monotherapy alone."
The CHMP opinion follows a review of three pivotal clinical trials. Results from these studies show that the single pill combination of telmisartan and amlodipine (TWYNSTA®):(2-7)
- in the 40-80mg/5-10mg formulation provides significantly greater blood pressure reduction compared to the respective monotherapies
- with the 80mg/10mg formulation, 82.7% of patients achieved their 24hr blood pressure goal (<130/80 mmHg according to the AHA criteria)
In addition, results from a recent trial in patients with severe hypertension (TEAMSTA severe HTN), showed that:
- the single pill combination of telmisartan and amlodipine (TWYNSTA®) reduces systolic blood pressure by a mean of nearly 50 mmHg. This powerful reduction, observed in nearly half of patients, is among the highest blood pressure reduction achieved in antihypertensive trials.(1)
Hypertension is a major CV risk factor and is responsible for more deaths than other factors, such as high cholesterol, diabetes or smoking. 11 Study results show that even a 2 mmHg reduction in systolic blood pressure decreases the risk of severe cardiovascular events like heart attacks and strokes by 7–10%.(12)
"We know that at least half of the patients miss at least one dose a month of their medication. We know that a third miss at least two doses a month. If we give them more tablets, they are more likely to miss more doses and that may mean that they are at much higher risk of stroke or of a heart attack," said Prof Thomas Unger, from the Charité Hospital in Berlin. "So, I would consider recommending this true once daily single-pill combination of telmisartan and amlodipine to a patient. I genuinely think that by improving a patient's blood pressure control, without having to increase the number of tablets, I could improve the likelihood of reducing his cardiovascular risk avoiding a stroke."
The single pill combination of telmisartan and amlodipine TWYNSTA® demonstrated in clinical trials that it is effective and well-tolerated in a range of more complex at-risk patients, as well as in those whose blood pressure was previously not controlled on monotherapy. (1-8) It contains telmisartan, the only ARB clinically proven in reducing the risk of cardiovascular death, myocardial infarction, stroke, and hospitalisation for congestive heart failure in a broad cross-section of high-risk cardiovascular patients.(9,10)
Once approved, the single pill combination of telmisartan and amlodipine (TWYNSTA®) will be available in a flexible range of dosing regimens enabling physicians to tailor treatment to individual patient needs.
TWYNSTA® was approved by the FDA on 19 October 2009 for the treatment of hypertension, alone or with other antihypertensive agents, and as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals.
About TWYNSTA® placebo-controlled factorial study, TEAMSTA-5 and TEAMSTA-10
The CHMP positive opinion of TWYNSTA® is based on the results of the following studies:(1-8)
- Randomised, double-blind, placebo-controlled factorial design trial of 1,461 patients with mild to severe hypertension
- Randomised, double-blind, active-controlled study of 1,097 patients with mild to severe hypertension who were not adequately controlled on amlodipine 5mg (TEAMSTA-5) and received TWYNSTA® tablets (40/5mg or 80/5mg) or amlodipine alone (5mg or 10mg)
- Randomised, double-blind, active-controlled study, a total of 948 patients with mild to severe hypertension who were not adequately controlled on amlodipine 10mg (TEAMSTA-10) and received TWYNSTA® tablets 40mg/10mg or 80mg/10mg or amlodipine 10mg alone.
About telmisartan (Micardis®/Kinzal®/Pritor®)
Telmisartan is a modern member of the Angiotensin II Receptor Blocker (ARB) class and has been investigated in the most ambitious and far-reaching research programme conducted with an ARB. In the clinical trial programmes ONTARGET™, PROTECTION™ and PRoFESS®, over 58,000 patients were enrolled to investigate the efficacy and cardiovascular protective effects of telmisartan.
Telmisartan was discovered and developed by Boehringer Ingelheim. Under the trademarks MICARDIS® and MICARDISPLUS® (combination with hydrochlorothiazide) the company markets telmisartan in 84 countries around the world, including the USA, Japan and European countries. Telmisartan is marketed in cooperation with Astellas Pharma Inc. in Japan, Bayer HealthCare in Europe and GlaxoSmithKline in selected markets.
Astellas Pharma Inc. co-promotes telmisartan under the trademark MICARDIS®, Bayer HealthCare promotes telmisartan under the brand names Kinzalmono®, Kinzalkomb® (combination with hydrochlorothiazide), and Pritor® and PritorPlus® (combination with hydrochlorothiazide) in markets across Europe. Pritor® and PritorPlus® is also marketed by GlaxoSmithKline in selected markets.
About Boehringer Ingelheim
The Boehringer Ingelheim group is one of the world's 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 142 affiliates in 50 countries and more than 41,500 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.
In 2009, Boehringer Ingelheim posted net sales of 12.7 billion euro while spending 21% of net sales in its largest business segment Prescription Medicines on research and development.
1. Neutel JM, Mancia G, et al. Single-pill combination of telmisartan 80 mg/amlodipine 10 mg provides superior blood pressure reductions in patients with severe hypertension: TEAMSTA Severe HTN Study.Poster presentation at the European Society of Hypertension (ESH), June 2010.
2. White B et al. Effects of telmisartan and amlodioine in combination on amulatory blood pressure in stages 1 -2 hypertension Blood Pressure. epub Blood Pressure Monitoring 2010.
3. Littlejohn J, et al. Results of treatment with telmisartan-amlodipine in Hypertensive Patients. J Clinl Hypertens 2009;11:4:207-213.
4. Neldam S, Lang M, et al. Fixed-dose combination therapy with telmisartan and amlodipine 5 mg in non-responders to amlodipine 5 mg provides superior blood pressure reductions to, and is associated with less peripheral oedema than, amlodipine 10 mg. Poster presentation at the American Society of Hypertension (ASH), May 2009.
5. Neldam S, Edwards C, et al. Investigators. Switch to a fixed-dose combination therapy with telmisartan and amlodipine provides significant blood pressure reduction and control in patients not adequately controlled with amlodipine 10 mg. Poster presentation at the American Society of Hypertension (ASH), May 2009.
6. Neldam S, Lang M, et al. Long-term safety and efficacy of single-pill combinations of telmisartan 40 - 80 mg plus amlodipine 5 mg in patients initially not controlled on amlodipine 5 mg: open-label follow-up of the TEAMSTA-5 study (TEAMSTA-5 follow-up). Poster presentation at the European Society of Hypertension (ESH), June 2010.
7. Neldam S, Edwards C, et al. Long-term safety and efficacy of single-pill combinations of telmisartan 40 - 80 mg plus amlodipine 10 mg in patients not initially controlled on amlodipine 10 mg: open-label follow-up of TEAMSTA-10 study (TEAMSTA-10 follow-up). Poster presentation at the European Society of Hypertension (ESH), June 2010.
8. Littlejohn T, Ruilope LM, et al. Telmisartan in combination with amlodipine provides a highly effective and well-tolerated treatment option for hypertensive patients with diabetes: sub-analysis from a factorial design study. Poster presentation at the European Society of Hypertension (ESH), June 2009.
9. The ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. New England Journal of Medicine 2008;358(15):1547-59.
10. MICARDIS SmPC 2010.
11. Lopez AD, et al. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet 2006;367:1747–1757.
12. Lewington S, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-13.