Aliskiren fails to show benefit for heart failure patients with diabetes

In continuation of my update on Aliskiren   and  Enalapril

 Enalapril  Aliskiren

A subgroup analysis in heart failure patients with diabetes from the ATMOSPHERE trial has failed to show benefit and signals the end of the road for aliskiren in heart failure. The findings were presented for the first time today in a late breaking trial session at Heart Failure 2016 and the 3rd World Congress on Acute Heart Failure.

"This was a subgroup analysis with the inherent limitations of this type of study. It failed to show superiority or non-inferiority of aliskiren over the angiotensin-converting enzyme (ACE) inhibitor enalapril in heart failure patients with diabetes," said principal investigator Professor Lars Kober, a consultant cardiologist at Rigshospitalet - Copenhagen University Hospital in Copenhagen, Denmark.

He continued: "The result may have been positive had the European Medicines Agency (EMA) not asked us to withdraw patients with diabetes from the trial. We will never know, as the angiotensin receptor neprilysin inhibitor LCZ696 has since emerged and bypassed the need for aliskiren."

Aliskiren is a renin-angiotensin-aldosterone system inhibitor that is used in patients with hypertension. The Aliskiren Trial of Minimizing OutcomeS for Patients with HEart failure (ATMOSPHERE) included 7016 patients with heart failure and reduced left ventricular ejection fraction, of whom 2340 were randomly assigned to enalapril plus aliskiren, 2340 to aliskiren, and 2316 to enalapril. Of these, 1944 (27.7%) had diabetes and 5072 (72.3%) were non-diabetics. The main study results were published in April and showed that aliskiren was not superior or non-inferior to standard treatment with an ACE inhibitor.

Following the results of two separate trials, the EMA requested the withdrawal of all patients with diabetes from ATMOSPHERE. The Aliskiren Trial in Type 2 Diabetes Using Cardiorenal Endpoints (ALTITUDE) had been stopped after patients with diabetes and a high risk of cardiovascular events were found to have an excess risk of cardiovascular and renal events with aliskiren. The Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) had found a tendency towards harm in patients with diabetes.

The current study is a prespecified subgroup analysis of ATMOSPHERE according to baseline diabetes status. Due to the premature withdrawal of patients with diabetes from the study drug, median follow-up was shorter in those with diabetes than those without (24.1 months versus 46.0 months; p<0.0001).

The investigators found that the effect of aliskiren on the primary endpoint of cardiovascular death or hospitalisation for heart failure did not significantly differ by baseline diabetes status. In those with diabetes, the primary endpoint occurred in 196 (29.5%) patients in the combination group, compared to 216 (33.1%) in the enalapril group (hazard ratio [HR] 0.86; 95% confidence interval [CI] 0.71-1.04; p=0.13), and in 172 (27.4%) patients in the aliskiren group (HR 0.82; 95% CI 0.67-1.00; p=0.053 compared with enalapril).

Regarding the safety of aliskiren in patients with diabetes, compared with enalapril it was associated with a lower risk of symptomatic hypotension (6.7% versus 10.0%; p=0.04). Other adverse events were evenly distributed.

Professor Kober said: "Aliskiren monotherapy looked promising in heart failure patients with diabetes, with an 18% almost significant reduction in cardiovascular death or heart failure hospitalisation compared to enalapril. There was a lower rate of symptomatic hypotension and no increase in other adverse events. This suggests that aliskiren could be an alternative for patients who cannot tolerate an ACE inhibitor."

Combination therapy with aliskiren and enalapril was associated with more adverse events compared with enalapril alone. As the two drugs together did not produce a better outcome, the trial does not support the combination of an ACE inhibitor and aliskiren.

Professor Kober said: "We did a rigorous trial which should have shown that aliskiren is as good as an ACE inhibitor. The drug was never given the chance to demonstrate how good it is because of regulatory interference. That will never be tested now. This could have been a major problem for patients if the neprilysin inhibitor had not emerged."

Valturna gets FDA approval .....

FDA, has approved Valturna (valsartan & aliskiren respective structures above) tablets, the first and only medicine to target two key points within the renin system, also known as the renin angiotensin aldosteronesystem (RAAS), an important regulator of blood pressure. This is the first approval for Valturna, which is indicated for the treatment of Hypertension (high blood pressure) in patients not adequately controlled on aliskiren or angiotensin receptor blocker (ARB) monotherapy and as initial therapy in patients likely to need multiple drugs to achieve their blood pressure goals. This unique combination brings together the powerful blood pressure lowering effects of valsartan and aliskiren. Valturna combines in a single pill valsartan, the active ingredient in Diovan((R)), the number one selling branded Hypertension medicine worldwide, and aliskiren, the active ingredient in Tekturna((R)), the only approved direct renin inhibitor (DRI). Valturna offers significantly greater blood pressure reduction than either valsartan or aliskiren alone. Now for the first time, patients have a treatment option in one pill that targets two key points of the RAAS, which may be overactive in many hypertensive patients. The important fact about the combination is - by targeting two key points within the RAAS, Valturna helps blood vessels relax and widen so blood pressure is lowered. Research suggests that up to 85% of hypertensive patients may need multiple medications to help control their blood pressure, underscoring the need for effective combination treatments, hope this combined drugs will help the patients to a large extent. But those people with stroke, heart attack, heart failure, kidney failure or eye problems resulting from hypertension will have to wait for some more time....

Ref : http://www.novartis.com/newsroom/media-releases/en/2009/1342100.shtml

Noden Pharma Announces FDA Approval of Tekturna (aliskiren) Oral Pellets for the Treatment of Hypertension in Adults and Children 6 Years of Age and Older

In continuation of my update on Tekturna (aliskiren)

Noden Pharma DAC, a global specialty pharmaceutical company that is focused on acquiring prescription medicines across a broad range of therapeutic areas, announced today the approval by the U.S. Food and Drug Administration of Tekturna (aliskiren) Oral Pellets for the treatment of hypertension in adults and children six years of age and older. The new formulation and pediatric indication were approved through the FDA priority review process. Noden Pharma DAC.

"This expanded indication for Tekturna provides an additional option for pediatric hypertensive patients," said Alan Markey, acting CEO of Noden Pharma DAC. "In addition, it provides an alternative dosing option for adults with hypertension."

According to hypertension guidelines published by the American Academy of Pediatrics (AAP) the prevalence of clinical hypertension in children and adolescents is ~3.5%. The prevalence of persistently elevated blood pressure is ~2.2% to 3.5%, with higher rates among children and adolescents who are overweight and those with obesity.^1‍

The efficacy and safety of Tekturna® for pediatric use was evaluated in an 8-week randomized, double-blind trial in 267 hypertensive patients 6 to 17 years of age, including 208 patients treated for 52 weeks, following the 8-week study. During the initial dose-response phase, Tekturna® reduced both systolic and diastolic blood pressure in a weight-based dose-dependent manner. These studies did not reveal any unanticipated adverse reactions. Adverse reactions in pediatric patients six years of age and older are expected to be similar to those seen in adults.

Tekturna® Oral Pellets may be taken by carefully opening the dispensing capsule and emptying the contents into a spoon then into the mouth, and then swallowing right away with water or milk (dairy or soy-based) without chewing or crushing. Alternatively, the contents can be taken orally immediately after mixing with specified dosing vehicles.

John McLaughlin, CEO of PDL BioPharma, said, "Our investment in Noden has provided us with a platform upon which to build a specialty pharmaceutical company, and we are pleased to see the team at Noden execute this important expansion of the label for Tekturna®."

Noden plans to make Tekturna® Oral Pellets available in 2018.

Noden Pharma Announces FDA Approval of Tekturna (aliskiren) Oral Pellets for the Treatment of Hypertension in Adults and Children 6 Years of Age and Older

FDA Approves Vostally (ramipril) Oral Solution for the Treatment of Hypertension in Adults

Rosemont Pharmaceuticals, Inc. announced  the U.S. Food and Drug Administration (FDA)  approval of  Vostally (ramipril) Oral Solution, an angiotensin converting enzyme (ACE) inhibitor that offers once-daily dosing in an oral liquid form for patients who have difficulty swallowing.

Vostally is indicated for the treatment of hypertension in adults, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. Additionally, in patients 55 years or older at high risk of developing a major cardiovascular event, Vostally is indicated to reduce the risk of myocardial infarction, stroke, or death from cardiovascular causes. Also, in adult patients with post-myocardial infarction heart failure, Vostally is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure.

Vostally is contraindicated in patients with a history of angioedema or hypersensitivity to this product or any other ACE inhibitor and in patients with hereditary or idiopathic angioedema. Vostally is contraindicated in combination with a neprilysin inhibitor (e.g., sacubitril). Do not administer Vostally within 36 hours of switching to or from sacubitril/valsartan, a neprilysin inhibitor. Do not co-administer Vostally with aliskiren in patients with diabetes.

“We are proud to bring Vostally to physicians to treat patients who may benefit from an ACE inhibitor but whose difficulty swallowing a tablet creates a barrier to this kind of therapy,” said Jeff Bryant, President of Sabal Therapeutics, a Rosemont Company. “This oral liquid form of ramipril provides physicians with another option for treating patients.”

“This FDA approval of Vostally marks an important milestone in expanding treatment options for patients who have difficulty swallowing traditional tablets or capsules,” continued Mr. Bryant. “We are proud to support Rosemont’s commitment to delivering high-quality oral liquid medicines to the U.S. market and believe Vostally will provide a meaningful benefit to both patients and healthcare providers and payors.”

Vostally will be available later this year. Full Prescribing Information, including boxed warning and safety profile, is available at www.RosemontPharmaceuticals.com.

https://en.wikipedia.org/wiki/Ramipril

FDA Approves Vostally (ramipril) Oral Solution for the Treatment of Hypertension in Adults

FDA Approves Widaplik (telmisartan, amlodipine and indapamide) for the Treatment of Hypertension

George Medicines, a late-stage biopharmaceutical company focused on addressing unmet needs in cardiometabolic disease, announced  the US Food and Drug Administration (FDA)  approval of  Widaplik™ (telmisartan, amlodipine and indapamide), formerly known as “GMRx2”, for the treatment of hypertension in adult patients, including as initial treatment, to lower blood pressure.

Widaplik is a proprietary single pill combination of three medicines: telmisartan, amlodipine and indapamide and is available in three doses: a standard dose and two low doses. It is the first and only FDA-approved triple combination medication for use as an initial therapy in patients likely to need multiple drugs to achieve blood pressure goals. Widaplik, with its three different doses, can deliver the efficacy benefits of a triple mechanism approach early in the treatment pathway with an established safety profile and good tolerability.

Indapamide

Amlodipine

Globally recognized treatment guidelines now recommend the use of single pill combination therapy for most patients and acknowledge the benefit of early use of combination therapy.

In the US, nearly half of adults have hypertension and only around one in four have their blood pressure under control. Hypertension is a major risk factor for coronary heart disease, stroke and heart failure and is estimated to cause 460,000 deaths in the US each year.

Mark Mallon, Chief Executive Officer of George Medicines, said: “Data show that most patients with hypertension will require two or more medicines to bring their blood pressure under control. Widaplik can provide patients with hypertension, including those who are starting treatment, with a different approach to control their blood pressure. With its triple combination efficacy, established safety profile, good tolerability and its availability in a single pill, Widaplik has the potential to address key challenges in current hypertension treatment approaches. With planning underway for the upcoming US commercial launch of Widaplik, and further regulatory submissions in other territories anticipated during 2025, George Medicines is well-positioned to positively impact the global burden of hypertension.”

Dr. Paul Whelton, Show Chwan Chair of Global Public Health at Tulane University, New Orleans, Louisiana, and Past President of the World Hypertension League, said: “I am very excited and pleased to have Widaplik approved for the treatment of hypertension in the US. Single pill combination antihypertensive therapy has great potential to improve hypertension control in the US and worldwide. Most patients with hypertension need multiple therapies to achieve their blood pressure goals. The new dose options available with Widaplik offer a treatment regimen that could benefit a broad range of patients, including those just starting treatment.”

The FDA approval is based on positive results from two international Phase 3 trials, which compared Widaplik against placebo and against dual combinations of its component drugs.

In both trials Widaplik significantly improved blood pressure and control rates vs comparators. In clinical trials, the most common adverse event reported in patients treated with Widaplik is symptomatic hypotension. Widaplik is contraindicated in patients with anuria, known hypersensitivity to telmisartan, amlodipine, indapamide, or to other sulfonamide-derived drugs, or to any other component of this product. In patients with diabetes, Widaplik is not to be co-administered with aliskiren. A boxed warning in the labeling informs physicians and patients to discontinue Widaplik as soon as possible after pregnancy is detected due to fetal toxicity.

The US commercial launch of Widaplik is anticipated in Q4 2025.

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 Widaplik 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.

George Medicines is backed by George Health, the commercial arm of The George Institute, and Brandon Capital, Australia’s leading life sciences venture capital firm.

About Widaplik™ (GMRx2)

Widaplik is a combination tablet of telmisartan, an angiotensin II receptor blocker, amlodipine, a dihydropyridine calcium channel blocker and indapamide, a thiazide-like diuretic, available in three dosage forms – 10/1.25/0.625 mg; 20/2.5/1.25 mg and 40/5/2.5 mg. Widaplik is indicated for the treatment of hypertension, including as initial treatment, to lower blood pressure.

Its development is backed by a comprehensive clinical program, including two pivotal Phase 3 studies, published in 2024 in the Journal of the American College of Cardiology and The Lancet.

In these trials the triple combination demonstrated significantly reduced blood pressure (BP) and improved BP control rates, when compared against dual therapy and against placebo. In both trials, tolerability was good, with no increase in withdrawal from treatment due to adverse events.

GMRx2 was investigated in the Nigerian VERONICA trial, which compared the triple combination with standard of care and reported better BP lowering among those receiving GMRx2, with good tolerability compared to the standard of care protocol.

A global trial investigating the potential of GMRx2 for the prevention of stroke in people who have had intracerebral hemorrhage (the most severe type of stroke) is ongoing.

INDICATIONS

Widaplik is a prescription medicine used to treat high blood pressure (hypertension) in adults. Widaplik may be used as the first medicine to lower your high blood pressure if your healthcare provider decides you are likely to need more than one medicine. Medicines that lower your blood pressure may lower your chances of having a stroke or heart attack.

https://en.wikipedia.org/wiki/Indapamide

https://en.wikipedia.org/wiki/Amlodipine

FDA Approves Widaplik (telmisartan, amlodipine and indapamide) for the Treatment of Hypertension