Gossamer could put pressure on Merck
Following the hit in the pivotal Stellar trial, sotatercept is on course to become the first disease-modifying therapy for pulmonary arterial hypertension. At least, that’s what its developer Merck says – but there are several more projects in development for this rare disease that might give Merck a run for its money.
In terms of late-stage readouts the most immediate threat to Merck comes from United Therapeutics, an already entrenched PAH player with two further products in phase 3. But more innovative agents, designed to address the causes of the disease, are also in the works.
Pulmonary arterial hypertension is not simply high blood pressure in the lungs. It is a chronic disease that causes the walls of the arteries of the lungs to narrow and stiffen. This forces the right ventricle to work harder to pump blood through the lungs, and the extra stress causes heart disease.
Currently it is treated either with endothelin receptor antagonists, PDE 5 inhibitors, prostacyclin analogues or soluble guanylate cyclase stimulators, all of which fundamentally work as vasodilators. Many of the clinical-stage projects in development for PAH also ultimately work like this.
Smoking worsens outcomes in PAH, especially for men, in REVEAL study
Cigarette smoking in men newly diagnosed with pulmonary arterial hypertension (PAH) was associated with a faster time to in-patient hospitalization and death after diagnosis, according to an analysis of the REVEAL study in the U.S.
More men smoked than women, and ever-smoking status (someone who has been a cigarette smoker) was associated with worse lung function, reduced physical abilities, impaired kidney function, and older age at PAH diagnosis.
“This is the largest report of prevalence and associated outcomes of smoking in PAH patients in the United States,” the researchers noted.
The REVEAL analysis was published in The Journal of Heart and Lung Transplantation in the study “Smoking history and pulmonary arterial hypertension: demographics, onset, and outcomes.”
PAH is marked by high blood pressure, or hypertension, caused by the narrowing of the pulmonary arteries, the small blood vessels that transport blood through the lungs.
Cigarette smoking is a well-established risk factor for diseases affecting blood vessels, including those of the pulmonary arteries. However, studies examining the prevalence and associated outcomes of cigarette smoking in PAH are scarce and conflicting.
Recently, a European registry analysis suggested that worse outcomes in people with idiopathic PAH (without a known cause) were related to smoking history and a low DLCO — a measure of oxygen passing from the air sacs of the lungs into the blood.
Rare GDF2 mutation linked to idiopathic PAH in brother and sister
A rare mutation in the GDF2 gene was identified in two siblings, a boy and a girl, with pulmonary arterial hypertension (PAH), according to a recent case report.
The mutation, which each child inherited in both gene copies, resulted in a lack of the bone morphogenetic protein (BMP) 9 in the blood and low levels of a related protein, called BMP10.
Their parents, who each had one copy of the mutation, have no signs of the disease or other health concerns, but their BMP9 and BMP10 levels were low relative to healthy adults matched by sex.
The report, “A rare homozygous missense GDF2 (BMP9) mutation causing PAH in siblings: Does BMP10 status contribute?,” was published in the American Journal of Medical Genetics Part A.
The growth differentiation factor 2 — GDF2 — gene belongs to a group of genes responsible for producing BMPs, a family of growth factors important for maintaining tissue architecture throughout the body.
Mutations in GDF2, which encodes for BMP9, are known to cause PAH in adults and children, but only three cases have been described in pediatric patients to date, according to the research team in Canada and the U.K.
Aerovate Therapeutics Publishes results of phase 1 study evaluating AV-101 for the treatment of pulmonary arterial hypertension in ERJ ppen research
WALTHAM, Mass., Nov. 17, 2022 (GLOBE NEWSWIRE) -- Aerovate Therapeutics, Inc. (Nasdaq: AVTE), a clinical-stage biopharmaceutical company focused on developing drugs that meaningfully improve the lives of patients with rare cardiopulmonary disease, today announced the publication of Phase 1 study results evaluating AV-101, a novel dry powder inhaled formulation of imatinib, in ERJ Open Research. The results showed that AV-101 was generally well tolerated and inhaled administration significantly reduced systemic exposure compared to orally dosed imatinib with no serious adverse events reported. AV-101 is being developed to address abnormal cellular proliferation and resistance to apoptosis in the pulmonary vasculature, which are key features of the pathophysiology of pulmonary arterial hypertension (PAH).
Imatinib is an anti-proliferative drug initially approved for the treatment of chronic myeloid leukemia. It has previously demonstrated a statistically significant and clinically meaningful benefit in PAH patients in the global Phase 3 IMPRES trial, conducted by Novartis, when administered orally as a tablet but was poorly tolerated due to adverse events. The development of imatinib for PAH was discontinued. Aerovate designed AV-101 to deliver imatinib throughout the airways to more directly access the diseased blood vessels in the lung, at or above concentrations observed with the oral dose while limiting systemic exposure. This allows for the potential to maximize efficacy while limiting the adverse events observed with oral imatinib.
Few liver problems with opsumit in PAH patients: Real-world data
Real-world use of Opsumit (macitentan) was generally safe, with few liver-related toxicities seen, according to data from two registries largely made up of pulmonary arterial hypertension (PAH) patients.
Collective data from the two registries met a requirement from the U.S. Food and Drug Administration (FDA) for additional real-world safety data — especially relating to potential liver toxicity — after Opsumit’s regulatory approval.
As in clinical trials, the treatment also appeared to prolong survival and prevent hospitalizations.
The findings “go beyond the setting of clinical trials and capture real‐world use of this medication,” the researchers wrote.
The study, “Safety of macitentan for the treatment of pulmonary hypertension: Real‐world experience from the OPsumit USers Registry (OPUS) and OPsumit Historical USers cohort (OrPHeUS),” was published in Pulmonary Circulation.
Opsumit is a daily oral therapy designed to slow disease progression and prevent hospitalizations for PAH patients. Belonging to a class of medications called endothelin receptor antagonists, it works to widen the blood vessels that are characteristically narrowed in PAH.
It’s approval was based on findings from the pivotal SERAPHIN Phase 3 trial (NCT00660179), which showed that daily Opsumit was well tolerated and significantly reduced morbidity (e.g. lung transplant), PAH progression, and death.
Adding resistance training to diet and exercise program may aid adults with obesity, HFpEF
CHICAGO — Adding resistance training to caloric restriction and aerobic exercise training was safe and did not adversely impact cardiac or arterial structure and function in older adults with obesity and HF with preserved ejection fraction.
“Clinicians should consider adding supervised resistance training to improve skeletal muscle strength and muscle quality of older patients with obesity and HFpEF,” Peter H. Brubaker, PhD, professor and chair of the department of health and exercise science at Wake Forest University, told Healio.
Researchers conducted a randomized controlled, single-blind, 20-week trial that evaluated the impact of supervised resistance training added to caloric restriction and aerobic exercise training compared with caloric restriction and aerobic exercise only. The study included 88 adults with chronic HFpEF and a BMI of 28 kg/m2 or greater. Of those, 77 patients completed the trial.