The U.S. FDA has granted breakthrough device designation to Salvia Bioelectronics BV for its implantable neurostimulation system to treat chronic migraine. The designation, which provides for priority review and consultation with the agency on product development, underscores the need for effective treatments for the costly and debilitating condition.

Since the device is in early stage research and development, Eindhoven, Netherlands-based Salvia has not shared details about the device or a possible timeline for FDA submissions. According to a summary in a patent filing, the wireless system comprises a treatment pulse generator unit and an implantable electrode unit to provide neurostimulation therapy for headaches.

“The FDA breakthrough device designation of our neurostimulation system reflects the recognition of the large unmet medical need of patients suffering from refractory chronic migraine, and the potential of Salvia’s bioelectronic foil technology to address this,” said Wim Pollet, Salvia’s chief medical officer. “We look forward to working closely with the FDA to expedite the review process to accelerate the development of our therapy.”

Measuring bioelectronic foil test samples. Credit: Salvia Bioelectronics BV

Elaborating on the potential opportunity to help this group of patients, Salvia COO Daniel Schobben said the effectiveness of neurostimulation has been reported in the literature using off-label implant devices. “Off-label devices are not designed for the anatomy of the head, however, impacting their safety profile,” as frequent reoperations are needed, he told BioWorld via email. “This is where we come in. Our conforming bioelectronic foils are designed to enable safe application in the craniofacial region via a minimally invasive procedure.”

He added that the company will pursue CE marking in parallel with FDA approval.

Heavy toll

An estimated 144 million people worldwide suffer from chronic migraine, which is defined as 15 or more migraine headaches per month. Migraine is the leading cause of disability under age 50, affecting 1 in 7 individuals, the majority of them women. Symptoms include throbbing or pulsating pain, sometimes with nausea, vomiting and sensitivity to light, can last from hours to days.

The impact is huge. In addition to their physical toll, migraines cost the U.S. about $78 billion annually in health care and days lost from work and other activities. Patients with chronic migraine can spend between $8,500 to $9,500 to address their symptoms, with episodic migraine costing about $2,000 a year.

While there is no cure, there are FDA-approved medications aimed at preventing migraine attacks or relieving symptoms during an attack. Among them is Novartis AG’s Aimovig (erenumab), which prevents migraine in adults by blocking the activity of calcitonin gene-related peptide, a molecule involved in migraine attacks. Other drug treatments include Eli Lilly and Co.’s Reyvow (lasmiditan) for short-term treatment of migraine without or without aura and Allergan Inc.’s Ubrelvy (ubrogepant tablets) for immediate treatment of migraine with or without aura.

Other neuromodulation devices for migraine

There are also FDA-approved neuromodulation treatments for episodic migraine and cluster headaches, but none specifically designed to address chronic migraine.

Israel-based Theranica Bio-Electronics Ltd. makes a wireless, remote, electroneuromodulation device, Nerivio, for the acute treatment of episodic migraine. Cefaly Technology sprl, a Belgian medical device company, also targets episodic migraine with its Cefaly neuromodulation system.

Electrocore Inc.’s neurostimulator, Gammacore, was the first such device to receive FDA clearance to treat cluster headaches, in 2018. A rechargeable and reloadable version, known as Gamma Sapphire, is marketed to treat episodic cluster and migraine in adults.

Meanwhile, Neurolief Ltd., of Netanya, Israel, reported data in 2019 showing significant relief from migraine following treatment with Relivion, the first noninvasive neuromodulation system to target two major nerves where migraines originate.

Recent series A round

Founded in 2017, Salvia’s CEO, Hubert Martens, previously led Sapiens Steering Brain Stimulation, a Netherlands-based developer of deep brain stimulation technologies that was co-founded by Martens in 2011 and acquired by Medtronic plc in 2014. Pollet served as Sapiens’ medical director, while Schobben, who did not have an operational role in the company, helped raise public funding for the endeavor.

To date, the company has raised a total of $34.6 million to advance its neuromodulation technology. In September, it scooped up €26 million (US$31 million) in a series A round led by new investors Panakès Partners, Inkef Capital and Shs Gesellschaft für Beteiliungsmanagement. Also participating were Bom Brabant Ventures, Thuja Capital and Dolby Family Ventures. The funds were earmarked for further development of its platform to address known neural targets in chronic migraine.

According to Salvia, the total raised includes a €5 million deferred risk-bearing innovation credit from the Netherlands Enterprise Agency, part of the Dutch ministry of Economic Affairs and Climate Policy.