Attgeno AB today announced that it has received approval from the Swedish Medical Products Agency and the Swedish Ethical Review Authority to start a phase 2 clinical trial of its lead drug candidate Supernitro as a potentially lifesaving treatment for patients with acute pulmonary hypertension after cardiac surgery.
The Phase 2 study is an open-label, multi-centre, Phase 2 clinical trial to assess the safety and the dose-range efficacy of Supernitro on pulmonary vascular resistance (PVR) in patients with post-operative acute pulmonary hypertension. An acute increase in PVR after cardiac surgery is a feared condition that can lead to right heart failure and death. Supernitro is a new intravenous drug candidate that delivers nitric oxide (NO) to selectively reverse acute pulmonary hypertension.
Approval to start the Phase 2 study has been secured following the completion of all necessary safety and efficacy testing of Supernitro, including a recent successful Phase 1 study in healthy subjects. The study is planned to start in June 2022, enrolling up to 24 patients at the Sahlgrenska and Örebro University hospitals in Sweden, and results are expected by the end of 2022. Given that the study shows positive outcomes, Attgeno will aim to start a pivotal 3 study as soon as possible, including involvement of clinics in the US.
“Approval to start the phase 2 study is major milestone achievement for the company that since the study will help to provide a framework for the pivotal clinical development programme. This is the regulatory proof that the Supernitro technology is safe and tolerable and has potential to be a life-saving treatment,” says Per Agvald, CEO and co-founder of Attgeno.
The advantage of Supernitro, when infused into blood vessels, is that it releases nitric oxide extremely fast and can therefore be targeted to a specific organ. Intravenous infusion of Supernitro affects blood circulation in the lungs, where nitric oxide is released and dilates the blood vessels to counteract acute pulmonary hypertension. However, the dilatory effect of nitric oxide on lung blood circulation cannot be studied in healthy individuals.
“The reason for this is that the blood vessels in a healthy subject’s lungs are almost fully dilated and PVR is very low due to intact endogenous endothelial nitric oxide production. In most cardiopulmonary disease there is deficient nitric oxide production in the lungs, and pulmonary hypertension develops. Thus, to evaluate the effect of Supernitro on pulmonary circulation, tests must be performed on patients with acute pulmonary hypertension. Patients undergoing elective cardiac valve surgery are prone to develop this condition,” says Christofer Adding, CMO and co-founder of Attgeno.
Attgeno believes the study will confirm a selective effect on lung blood circulation and find suitable doses to design the pivotal randomised controlled trial studies needed for market authorisation.
“Attgeno’s invention, Supernitro, seems to have huge potential, not only in the treatment of life-threatening conditions when cardiac surgery with cardiopulmonary bypass elicits acute pulmonary hypertension, but also in several other diseases associated with increased risk of right heart failure. For decades, the scientific community has searched for a selective pulmonary vasodilator that could be administered intravenously, and if Supernitro really has this property in humans it should represent an enormous therapeutic advance,” says Sven-Erik Ricksten, professor in thoracic anaesthesiology at the Sahlgrenska Hospital, Gothenburg.
Attgeno AB is a privately held Swedish pharmaceutical development company devoted to commercialization of innovative and effective nitric oxide-donating drugs. Its leading drug candidate Supernitro (PDNO) is currently in clinical development Phase II. For further information, please visit www.attgeno.com.
About Supernitro (PDNO)
Supernitro is administered as an intravenous infusion, which upon entry into the blood, has an ultra-short half-life rapidly releasing its active moiety nitric oxide (NO). As a result, most of its NO is released just through the short passage through the lung blood circulation where it reacts with the blood vessels and causes them to dilate. By the donation of NO in the lungs, Supernitro replaces the decrease in NO production that is a well-known consequence of different diseases leading to increased risk for pulmonary hypertension.
About pulmonary hypertension
Pulmonary hypertension is a condition of increased blood pressure in the arteries of the lungs. Symptoms include shortness of breath, fainting, tiredness, chest pain, swelling of the legs, and a fast heartbeat. Onset is typically gradual and prognosis poor.
The pathogenesis of pulmonary hypertension involves the narrowing of blood vessels connected to and within the lungs. This makes it harder for the heart to pump blood through the lungs, as it is much harder to make water flow through a narrow pipe as opposed to a wide one. Over time, the affected blood vessels become stiffer and thicker, in a process known as fibrosis. The mechanisms involved in this narrowing process include vasoconstriction, thrombosis, and vascular remodelling.