In an addendum to a benefit assessment, the German Institute for Quality and Efficiency in Health Care (IQWiG) re-examined whether mavacamten has an added benefit over treatment of physician’s choice in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
The analyses now available show: There are advantages in morbidity and health-related quality of life. Overall, there is therefore a hint of considerable added benefit of the new drug in comparison with the appropriate comparator therapy.
The (German-language) addendum was published in February 2024, an English translation in April 2024.
First specific drug in the therapeutic indication
OHCM is a genetic disease of the heart muscle in which the walls of the left ventricle become thickened to such an extent that the ventricle is reduced in size. This narrowing blocks the blood flow out of this ventricle during systole (obstruction), which can lead to a backflow into the pulmonary veins. While some patients hardly notice anything, others experience reduced performance and other symptoms such as tiredness, shortage of breath, chest tightness, cardiac arrhythmias or dizziness. Younger patients in particular also have an increased risk of sudden cardiac death.
While surgery is a common treatment to remove severe obstructions, mavacamten, a drug that specifically relaxes the heart muscle, has recently become available for milder forms and patients with mild to moderate symptoms. The drug works by reducing the contraction of the heart, improving the filling and emptying of the left ventricle.
Decisive data on the study were subsequently submitted
In its 2023 dossier, the manufacturer had submitted data from the placebo-controlled EXPLORER-HCM study. Participants in this study received mavacamten or placebo in addition to non-vasodilating beta-blockers or calcium channel blockers of physician’s choice. Some patients had slight, and some more severe limitation of physical activity.
For many patients, however, it remained unclear whether the treatment of physician’s choice used in the study was appropriate. The manufacturer subsequently submitted information and analyses in the commenting procedure and after the oral hearing.
This solved the main problem, even if some uncertainties remain. No more than hints of an added benefit can therefore be derived from the study data.
Advantages in morbidity and health-related quality of life
In the category of morbidity, there is a hint of a minor added benefit of mavacamten plus treatment of physician’s choice compared with placebo plus treatment of physician’s choice for 2 outcomes, and a hint of a considerable added benefit for another outcome. In the category of health-related quality of life, there is an additional hint of a considerable added benefit. There are no hints of advantages or disadvantages of the new drug in the outcome categories of mortality and side effects.
In summary, there is a hint of considerable added benefit of mavacamten plus concomitant treatment of physician’s choice in comparison with the appropriate comparator therapy for patients with symptomatic oHCM (NYHA class II to III).
“This is a good result for this first specific oHCM drug,” says Volker Vervölgyi, Division Head in IQWiG’s Drug Assessment Department. “And it shows that the AMNOG procedure works. The subsequently submitted information provided transparency on the added benefit of mavacamten, in particular on its positive influence on quality of life. This assessment will therefore also support future treatment decisions in clinical practice.”
G-BA decides on the extent of added benefit
The dossier assessment is part of the early benefit assessment according to the Act on the Reform of the Market for Medicinal Products (AMNOG) supervised by the Federal Joint Committee (G-BA). After publication of the manufacturer’s dossier and the IQWiG dossier assessment, the manufacturer submitted additional information in the commenting procedure. The G-BA subsequently commissioned IQWiG to assess the data subsequently submitted. IQWiG now presents this assessment in the form of an addendum. The G-BA makes a final decision on the extent of added benefit.