Braincool AB has scored a breakthrough device designation from the U.S. FDA for its Cooral system, a medical cooling technology for therapeutic hypothermia and oncology. The status acknowledges Cooral’s potential to prevent oral mucositis (OM), a complication of chemotherapy.

OM is one of the most common and debilitating complications of cancer treatments, causing tissue swelling and ulcerations in the mouth. Patients with OM often experience weight loss and malnutrition, requiring the use of feeding tubes and total parenteral nutrition – leading to a further loss in quality of life. Open sores in the mouth can also provide an entry for infections that can lead to sepsis and death.

Analgesics and sometimes opioids, administered intravenously, may be prescribed to ease the discomfort, but patients often require hospitalization, adding to health care costs.

“The incremental cost of OM-associated hospitalization among stem-cell recipients is high, exceeding $70,000 for patients who develop ulceration and $375,000 among those with grade V mucositis (ulceration at four or more oral sites),” Martin Waleij, Braincool’s CEO, told BioWorld. Looking at general oncology solid tumors, there is a documented additional cost of around $3,700 per chemo cycle, and adding to that, further hospital stays.

Novel approach

Based in Lund, Sweden, Braincool has developed a single-use oral cooling device to prevent OM. The device connects to a portable cooling system and cools the oral mucosa, continuously circulating water through its closed conduits at a steady temperature to reduce blood flow and exposure of oral tissues to chemotherapeutic agents.

“This is a significant milestone for the Cooral system,” Waleij said. “Not only does this breakthrough designation safeguard a faster and smoother regulatory process as we enter the U.S. market, the new CMS reimbursement ruling is a vital mechanism for getting the device into clinical practice where it can actively benefit patients without further delay.”

Breakthrough device status is granted to medical devices that have potential to more effectively treat or diagnose life-threatening or irreversibly debilitating. Companies are entitled to increased feedback from agency staff regarding development and submissions and to priority review. They also benefit from recent CMS changes that provide coverage for FDA breakthrough devices.

Nordic trial

The FDA based its decision on results from the Nordic pivotal trial, a multicenter, randomized study in 182 patients with multiple myeloma or lymphoma who were scheduled to receive high-dose chemotherapy prior to hematopoietic stem cell transplantation. The study, presented at a late-breaking session of the 2020 European Society for Medical Oncology’s virtual meeting in September, showed Cooral to be as effective as ice chips in cryoprevention, with fewer than 10% of patients developing severe OM.

The effect was especially strong in lymphoma patients when compared with ice chips – mean total 1.77 vs. 3.08; p = 0.047 on the Oral Mucositis Assessment Scale – a significant finding given the long courses of treatment lymphoma patient face. In terms of tolerability, both groups of patients rated Cooral higher vs. ice chips.

Roger Henriksson, a professor at Umeå University, said oncologists need better cooling methods to prevent OM. “Cooling is a well-known method to prevent this chemo-induced side effect, but is it only limitedly applied in clinics because using ice water is painful for the patient and poorly tolerated during the entire treatment time. Risk of infection can also be a deterrent. The Cooral system is an important step forward and a much-needed technology.”

De novo pathway

The Nordic trial was the foundation was also the foundation for Cooral’s de novo 510(k) designation, Waleij told BioWorld. “We are committed to getting the product to the market quickly, and this [de novo] pathway is a priority for 2021.”

The company plans to launch Cooral internationally once the Nordic trial results have been published in a major scientific journal, expected sometime in 2021.

Beyond prevention of chemo-induced OM, the company is looking to extend Cooral’s use to radiation patients and to a product for preventing chemotherapy-induced peripheral neuropathy, another severe side effect of cancer treatment.

“Cooral system is a unique product and has no competitor on the market today, which was affirmed by a very rapid patent approval,” Waleij said. Further underscoring Cooral’s promise is FDA’s inclusion of the treatment in its Early Access Program, which provides access to investigational products with the potential to address previously unmet medical needs for severe or life-threatening diseases.