Pfizer conducted an interim futility analysis of their global Phase III trial, REALM-DCM, to test the efficacy and safety of emprumapimod (PF-07265803) in patients with dilated cardiomyopathy (DCM) due to a lamin gene mutation. Based on this analysis, Pfizer found that the trial is unlikely to meet its primary endpoint, leading the company to cease the development of emprumapimod.
According to GlobalData’s Cardiomyopathy Report and Sales Forecast to 2031, the cardiomyopathies market was expected to grow from $1.6bn to $5.2bn across the US, 5EU (five major European markets: France, Germany, Italy, Spain and the UK) and Japan from 2021 to 2031. Emprumapimod was projected to launch in 2027, generating $24.84m during its first year on the market and $127.83m by 2031. But due to the small population of DCM patients whose condition is caused by the mutation of this specific gene, the discontinuation of emprumapimod should not substantially affect projected cardiomyopathy drug sales, based on GlobalData’s report.
Cardiomyopathy is a term referring to a heterogenous collection of diseases that are characterised by impaired heart muscle. Subtypes include hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy, arrhythmogenic cardiomyopathy (ACM) and restrictive cardiomyopathy (RCM). DCM occurs when the left ventricle is enlarged and therefore cannot effectively pump blood out of the heart. Cardiomyopathies can either be inherited genetically or acquired due to behaviours or other conditions. By targeting DCM patients with lamin gene mutations, emprumapimod would have been a novel therapy option, as most currently available cardiomyopathy drugs are non-specific and used for a variety of indications. When asked about targeting gene-specific forms of cardiomyopathies, a GlobalData key opinion leader (KOL) in the US shared the following:
“There are still people that don’t have good responses to [currently marketed] medicines, and I think that genetic analysis is going to show us more and more about specific gene targets. For example, the lamin gene… we think that causes 8% of dilated cardiomyopathy, and we think that we may have a specific antidote for that. For most other genes, we do not. So, targeting certain genetic profiles, I think could be tremendously instrumental… and we’re just now looking into that.”
Although Pfizer’s portfolio does include other cardiovascular therapies, such as Aldactone (spironolactone), amiodarone hydrochloride, metoprolol tartrate and Accupril (quinapril hydrochloride), these drugs’ patents have long since expired. Emprumapimod was expected to launch across the US, 5EU and Japan over the forecast period (2021–31), acquiring a patient share of 0.077% of US DCM patients during the first year of market release. This share was expected to increase to 0.375% by 2031, or roughly 5,275 patients.
Without the launch of emprumapimod, there are no late-stage candidates for DCM. Aficamten is the only current late-stage pipeline cardiomyopathy therapy and is being developed for HCM, with Camzyos (mavacamten) launched earlier this year for HCM patients. Camzyos is the first novel therapy option available for cardiomyopathy patients in decades. With the discontinuation of emprumpaimod’s clinical trial development comes the need for cardiomyopathy therapies that target gene-specific mutations. Although there is not currently a drug poised to fulfil this unmet need, there has been an increased focus of research on the genetic inheritance of cardiomyopathies. Hopefully, this research will yield promising therapies for this complicated disease.