ICYMI: Cala Health’s Wearable for ET

Five years ago, Kate Rosenbluth, then a Stanford Biodesign fellow, was wandering the halls of Stanford Hospitals and Clinics in search of an idea for a project. As she followed folks around, she was struck by patients with a movement disorder called essential tremor (ET).

She had recently spent time at UCSF working on implanted brain stimulation, gene therapy, and opto-genetics for the better-known movement disorder Parkinson’s disease. At Stanford, “I realized that there was this tremendous unmet need,” she says.

In particular, it was the impact of tremors on patients’ quality of life that drove home the urgency of the need. “Here was a condition that had a tremendous impact on patients’ lives, and there was virtually nothing for them therapeutically between brain surgery, whether DBS or MR-focused ultrasound, and drugs, which were primarily off-label,” she says.

Rosenbluth and others on her team began by looking at the peripheral nervous system, hoping find a solution to the unmet need by conceiving of the human body as a neural circuit. “It turns out our nerves are just like the wires connecting a battery to the deep brain stimulator in our brain. We said, ‘What if we reimagined the peripheral nervous system to be those wires? Potentially, we’d be able to treat non-invasively the same site as deep brain stimulators, without brain surgery.” 

In patients suffering from essential tremors, the central tremor network in the brain suddenly goes haywire, Rosenbluth explains. Neurosurgeons use metal-tipped microelectrodes to find the site for implanting a deep brain stimulator by means of a procedure in which the circuits are audible. They push the electrodes down and can hear which cell structures they’re in by the sounds of the cells firing. When they reach a structure called the VIM (ventral intermediate nucleus of the thalamus), they hear a sound that is the tremor and implant the stimulator. As Rosenbluth and her team thought about the technology they were trying to develop, she says, “We knew that deep brain stimulation was incredibly effective in treating essential tremor if you stimulated the VIM and wondered if it might be possible to reverse engineer the tremor circuit and treat essential tremor at the wrist instead of the brain.” What they needed to do was to figure out both the spatial and temporal components of their approach. “We realized that spatially, it turns out that the median nerve, a nerve accessible right underneath the skin is a beautiful target for stimulation and actually connects up through the nervous system into the VIM,” she says.” The second, temporal, piece entailed using motion sensors like those found on an Apple Watch or FitBit to time each patient’s stimulation pattern to interrupt the circuit in the brain.

Cala Trio

Rosenbluth reached out to Scott Delp, PhD, a bioengineering professor well-versed in neuromodulation. They designed a wearable device that, sitting on the wrist, detects and treats essential tremors. One of the virtues of a wearable approach to ET is that a person’s level of tremors, like many neurological conditions, is highly variable throughout the day.

Rosenbluth and Delp launched Cala Health Inc. in July 2014 to commercialize its wrist-worn therapeutic device, Cala Trio, which, is intended for symptomatic or on-demand usage. “It’s been one of the big challenges in developing therapies for this condition that if you look hour-to-hour, someone’s tremor level will change immensely, she says. Assessing Cala’s own dosing, based on triggering a signal to interrupt the tremor, she adds, “What we found is that when we treated for about 40 minutes, the patient had relief through the 40 minutes and then for roughly an hour or so afterward.”

In Cala Health’s most recent study, conducted last fall, patients who achieved relief reported that that relief lasted 96 minutes after the 40-minute dosage. “What we saw was that 92% of the patients using it improved, and 54% of the patients using it saw a greater than 50% improvement in tremors,” she says.

Cala Trio is intended for symptomatic or on-demand usage. In the study, patients were instructed to use the device twice a day. Now commercially available, there’s no limit to how often the patient can use his or her device and, in fact, says Rosenbluth, “What we expect is that patient use will go all the way from only-as-needed, to over and over throughout the day to around the clock.”

Cala Health estimates that there are seven million people in the US who experience essential tremors but only about 10%, or around 725,000, actually see a physician about them, largely because of a lack of treatment options, says Renee Ryan, Cala Health’s recently-appointed CEO. (Rosenbluth, who was CEO until summer 2019, is now CSO and continues sitting on Cala’s Board of Directors.) “People are diagnosed with ET, typically to understand if they have Parkinson’s Disease.” she says. “They’ve tried drugs and some remain on them due to efficacy and side effects; some have quit the therapy.” Even when drugs like beta blockers work, physicians estimate they only work about half the time and have to be extremely highly dosed to be effective. “Most people try therapy but most don’t stay on therapy,” she says.

Part of figuring out Cala’s commercialization strategy lies in weighing the options of reimbursement and self-pay. Cala is pursuing reimbursement, though Ryan notes that an ablative procedure marketed by Insightec is charging $40,000 per surgical procedure for the treatment of essential tremors. Available since 2016, it is just starting to have insurance reimbursement. Other approaches to treatment, such as DBS and microwave-guided ultrasound, come with similar high price tags, which are, says Ryan “a lot more than what our solution will cost patients.”

A Biotech-like Model

Tapping into the 90% of the ET population that isn’t currently being treated offers Cala Health a huge opportunity with a patient population that is eager to find a treatment that works. But company executives see an even greater opportunity beyond ET in the treatment of chronic conditions more broadly. Ryan notes that fundamental to Cala’s approach is the concept of “electricity as medicine” or, as noted, “bioelectronic medicines.” “And,” she adds, “these additional chronic conditions "are on our road map."

That in turn makes the company’s business model notably different from that of most medtech start-ups. With multiple conditions to target, Cala Health begins to look more like a biotech company, Ryan argues, with the ability to enhance enterprise value significantly by out-licensing its technology to companies addressing markets outside of the movement disorder specialty market. “Maybe a market with a primary care or cardiologist call point, both of which are much larger that we can target as a start-up,” she says.

For Rosenbluth, Trio is the first effort in an expansive growth for neuromodulation. “You could say we’re a next step in the evolution of neuromodulation,” she says. “Modern electrical medicine arguably started with end-organ implants like the pacemaker in the 1950s, then more recently evolved to treating peripheral circuits with technologies like vagus nerve stimulators. “Now we’ve moved this to non-invasive devices laden with sensors, putting the patient at the center of care,” she says.

Read our full story about Cala Health in MedTech Strategist.

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