A phase 2 study investigating LAM-001, a novel inhaled formulation of sirolimus, for the treatment of pulmonary arterial hypertension (PAH) has been initiated, AI Therapeutics announced.

“Currently available therapies for PAH provide relief to patients predominantly through the reversal of vasoconstriction, but do not directly address the cellular remodeling that constitutes the underlying pathophysiology of the disease,” said Dr. Aaron Waxman, director of the pulmonary vascular disease program at Brigham and Women’s Hospital, and principal investigator of the trial.

The 24-week, single-arm, open-label, phase 2, exploratory study is set to evaluate the safety, tolerability, and efficacy of LAM-001 in 15 adult patients with PAH (classified as WHO functional class III) who are receiving treatment but still experience disease symptoms. After 24 weeks of therapy, there will be a 12-month extension period.

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“By modulating both the mTOR and BMPR2 pathways, LAM-001 has the potential to reduce smooth muscle cell hyperproliferation and ameliorate endothelial cell dysfunction in the pulmonary vasculature, thereby altering the long-term course of the disease. Even as new disease-modifying agents become available, because of its unique mechanism of action, LAM-001 may become an important addition to our growing armamentarium of drugs used to treat this devastating disease,” Waxman added.

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The researchers will monitor indicators of safety and tolerability as the primary endpoints, as well as the change from baseline in peak oxygen uptake at week 24, measured by invasive cardiopulmonary exercise testing. 

They will also evaluate ventilatory efficiency, cardiac output, cardiac index, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, pulmonary vascular resistance, pulmonary arterial compliance, pulmonary arterial distensibility, and arteriovenous oxygen content difference at 24 weeks as secondary endpoints.

The additional hemodynamic metrics will be measured through invasive cardiopulmonary exercise testing, while cardiac magnetic resonance imaging will be used to measure cardiac structure and function.

Moreover, the study will evaluate a change from baseline in 6-minute walk distance, change from baseline in WHO functional class, time to clinical worsening, and LAM-001 pharmacokinetics.

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“LAM-001 offers an innovative solution to delivering sirolimus directly to diseased lungs, thereby potentially minimizing systemic exposure. Systemic toxicities have heretofore precluded the widespread adoption of oral sirolimus in certain promising indications despite strong signals of clinical benefit. PAH represents one such orphan pulmonary disorder,” noted Dr. Brigette Roberts, chief executive officer of AI Therapeutics.

PAH affects approximately 30,000 patients in the United States. The condition has a rapid progression and a 5-year survival rate of approximately 57%.


AI Therapeutics announces initiation of a phase 2 clinical trial of LAM-001 for treatment of pulmonary arterial hypertension (PAH). News release. AI Therapeutics, Inc.; August 31, 2023.