Novel cell therapy CAP-1002 safe, shows promise in PAH: Trial

Efficacy measures support treatment’s potential to improve exercise capacity

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

Share this article:

Share article via email
A list on a clipboard shows the words

In people with pulmonary arterial hypertension (PAH), treatment with the novel cell therapy CAP-1002 was safe and showed encouraging efficacy, according to the results of a Phase 1a/b clinical trial.

In particular, exploratory efficacy measures supported the potential of CAP-1002 in improving cardiopulmonary function, including exercise capacity, in PAH patients.

“The most important takeaway is that this approach is safe and feasible to do in people with pulmonary arterial hypertension,” Michael I. Lewis, MD, director of respiratory care services at Cedars-Sinai Medical Center, in Los Angeles, and the study’s principal investigator, said in a press release.

“These are encouraging exploratory findings that motivate moving on to more advanced studies,” Lewis said.

The study, “The ALPHA phase 1 study: pulmonary ArteriaL hypertension treated with CardiosPHere-Derived allogeneic stem cells,” was published in the journal eBioMedicine.

Recommended Reading
This illustration shows a person making a choice of medicines.

Survey reveals patients’ preferences for treating PAH

CAP-1002 also being tested in Duchenne MD patients

PAH is a progressive disease characterized by high blood pressure in the blood vessels that supply the lungs, which makes the right ventricle of the heart work harder to pump blood.

Pulmonary vasodilators, which work by opening blood vessels to improve blood flow, are one of the mainstays in PAH therapeutics. However, despite treatment, some patients still have blood vessel blockages and problems in the heart’s right ventricle.

Cardiosphere-derived cells or CDCs — progenitor heart cells that are able to release signaling molecules to promote heart health — were first discovered by Eduardo Marbán, MD, PhD, a pioneering heart researcher, and his team at Cedars-Sinai.

CAP-1002, made of CDCs, which are derived from the heart tissue of a healthy donor, is being tested as a treatment for several diseases, including Duchenne muscular dystrophy.

“Although several drugs are approved for pulmonary arterial hypertension, mortality remains high,” said Marbán, the executive director of the Smidt Heart Institute at Cedars-Sinai, and the study’s senior author.

“We tried a fundamentally different approach — cell therapy delivered into the pulmonary artery — and found encouraging results, in patients already on combination conventional therapy,” Marbán said.

The ALPHA Phase 1a/b study (NCT03145298), which enrolled patients with pulmonary arterial hypertension on PAH-specific medication, primarily assessed the safety of CAP-1002 infusions.

Women with PAH comprised 77% of the study’s participants. Idiopathic PAH, when the disease has no identified cause, was the predominant PAH subtype, seen in 61.5% of these patients.

Although several drugs are approved for pulmonary arterial hypertension, mortality remains high. … We tried a fundamentally different approach — cell therapy delivered into the pulmonary artery — and found encouraging results, in patients already on combination conventional therapy.

The study was divided into two phases. The first was a dose-escalation Phase 1a part, in which six participants with PAH received CAP-1002 administered at a dose of 50 million CDCs (three patients) or 100 million CDCs (three patients). This trial phase was open-label, meaning that both participants and researchers knew which dose was being given to each patient.

In the second Phase 1b portion, 20 PAH patients were randomly assigned to CAP-1002 with 100 million CDCs or a placebo; 10 were in each group. The mean age of those in the treated group was 53, while the participants in the placebo group had an average age of 56.

According to the researchers, 100 million CDCs is the maximum feasible dose from a manufacturing perspective.

The patients were followed for 12 months (one year). Exploratory efficacy analyses focused on data at two and four months, and included assessments of blood flow in the heart and lung with right heart catheterization and heart MRI scans, and pulmonary function tests.

Safety data revealed no adverse events during follow-up, including hospitalizations for PAH worsening or heart failure.

Recommended Reading
Banner for Karen Schultz's column

Even after 20 years, ordering PAH medications involves frustrations

Gains in walk distance test seen for over 40% of patients on CAP-1002

Exploratory analysis of the trial’s second phase showed promising signs supporting the potential therapeutic benefits of CDC infusions.

“It should be emphasized that these positive observations occurred with both 50 and 100 million cell doses of CDCs,” the scientists noted, calling the findings “encouraging.”

“We thus felt comfortable pooling all CDC results to increase statistical power,” they wrote.

Cardiac MRI scans showed improvements in right heart function with CAP-1002 compared with the placebo. This was accompanied by enhanced exercise capacity within two months of the infusion, as assessed by the six-minute walk distance test (6MWD). Those results, however, were not sustained at four months.

Improvements in 6MWD superior to 33 meters (108 feet), the minimal important difference for naïve or untreated PAH patients being tested on a new medication, were found in up to 43.75% of CAP-1002 patients compared with 20% of those on the placebo.

Lung function, measured by the diffusing capacity for carbon monoxide — the ability of the lungs to transfer oxygen from air to the bloodstream — declined in the placebo group, but was preserved with CAP-1002 at four months.

In contrast, no differences were seen in mean pulmonary artery pressure or pulmonary vascular resistance, a measure of the resistance to blood flow.

Blood levels of creatinine — a kidney disease biomarker — after four months were reduced in patients infused with CAP-1002 and unchanged in the placebo group.

“We speculate this may reflect a direct impact of CDCs on the kidney,” the investigators wrote.

Overall, “CDCs merit further study as adjunctive [add-on] therapy to improve outcomes in PAH,” the researchers wrote. Supported by the positive findings in Duchenne, the researchers now are planning further studies to “test repeated infusions of CDCs in patients with PAH with intermediate to high-risk characteristics.”

“Because only single CDC doses were used here, the findings represent a lower limit estimate of CDC’s potential in PAH,” they added. “Upcoming Phase 2 studies would logically use a repeat dosing paradigm.”

A Conversation With Rare Disease Advocates