Sonivie Ltd. has won breakthrough device designation from the U.S. FDA for the Therapeutic Intra-Vascular Ultrasound (TIVUS) system for renal artery denervation (RDN) to treat resistant hypertension. At the same time, the company revealed that it has bought the remaining intellectual property and other assets related to the use of the TIVUS System from Cardiosonic Inc. Sonivie previously licensed technology related to the use of TIVUS specifically in the treatment of pulmonary arterial hypertension (PAH).

Resistant hypertension is defined as blood pressure that remains above 140/90 mmHg despite use of three antihypertensive medications of different classes at the best tolerated doses, one of which must be a diuretic.

Renal denervation with the TIVUS system is a minimally invasive procedure that uses high-frequency, non-focused ultrasound to ablate nerves in the renal artery. This causes a reduction in the nerve activity, which decreases blood pressure.

Cardiosonic previously conducted two clinical trials of RDN in resistant hypertension patients using an earlier version of the TIVUS system. Results showed excellent feasibility in lowering blood pressure out to six months. The company gained a CE mark for the earlier version of the system.

Sonivie gained breakthrough device designation for the TIVUS system in the treatment of PAH in September 2019. The disorder is characterized by abnormally high blood pressure in the pulmonary arteries, which are responsible for carrying blood from the right side of the heart through the lungs. This forces the right heart to work harder, causing the heart muscle to weaken or even eventually fail.

In October, Sonivies said it had gained a green light from the FDA for its IDE for a pivotal study of the TIVUS system in those with PAH. Sonivie, which has a presence in Boston and Rosh Ha’ayin, Israel, presented positive 12-month safety and efficacy data from the earlier TROPHY1 study earlier this year at the EuroPCR and American Thoracic Society virtual meetings.

Asset buy

When asked why the company decided to buy the rest of the IP and assets at this time, Chuck Carignan, CEO of Sonivie, told BioWorld that when he joined the company in 2019, he thought it would make more sense to have one entity to develop the clinical applications in PAH and resistant hypertension, as the same console and catheter are involved – albeit through slightly different algorithms.

He noted that Medtronic plc and Recor Medical Inc. had published positive results related to RDN and Cardiosonic had fantastic data for blood pressure reduction. Combine that with having the data in hand for PAH, Carignan saw a great opportunity.

“I thought there were good synergies to leverage and bring more value to Sonivie and its investors, as adding the additional indication was largely only clinical execution and not a lot of extra R&D work that could be a distraction – same hospitals and same interventional cardiologist would do both procedures.”

He noted that there is a great opportunity for the system, as the U.S. PAH population stands at about 100,000 patients. Meanwhile, the resistant hypertension market is about 9 million, “of which we think at least 2 million are good candidates for TIVUS RDN,” he added.

The company now is focused on completing U.S. trials for eventual approval – something that should support additional CE marks. The company hopes to wrap up enrollment and follow-up in the PAH study in late 2022, with an approval coming the next year.

Other companies, as Carignan noted, could enter the field. In March, for example, Medtronic reported results of the pivotal Spyral-HTN OFF MED study at the American College of Cardiology's Annual Scientific Session that demonstrated significant reduction in blood pressure three months after RDN in patients with unmedicated hypertension. The results were published simultaneously in The Lancet.

The company’s Symplicity Spyral system received breakthrough device designation from the FDA March 27. That was good news for this company, which in 2014 saw its SYMPLICITY HTN-3 trial, which used the earlier version Symplicity Flex, fail to hit its primary efficacy endpoint. As a result, Medtronic suspended enrollment in other SYMPLICITY trials around the globe.

Last year, Recor Medical Inc. reported six-month “on-medication” results from its RADIANCE-HTN SOLO trial, showing patients treated with the Recor Paradise ultrasound denervation system were prescribed fewer antihypertensive drugs and had larger blood pressure drops than those treated with a sham procedure. Results appeared in the March 29, 2019, issue of Circulation. The company is currently conducting a pivotal study, RADIANCE-II, to build on the RADIANCE-HTN SOLO results and assess patients with moderate hypertension.