SetPoint Medical Sets its Sights on Treating Multiple Sclerosis

by Victor Pikov, contributing editor

April 2024 issue, BioElectRx Business Report

SetPoint Medical, the Valencia, CA manufacturer of bioelectronic medicine systems, is rightfully considered the pioneer in the field. Since the company’s founding in 2007, it gradually grew to employ more than 80 people and raise more than $300 million in capital to date. The initial market for SetPoint’s VNS therapy is rheumatoid arthritis, with the PMA approval expected next year.

With its pivotal PMA clinical trial approaching completion, SetPoint has set its sight on the second potential market—multiple sclerosis. Let’s take a look at that market to assess its attractiveness from clinical and financial points of view.

RA is a systemic autoimmune disease caused by overactivity of the immuno-competent organs, such as the spleen, which produce excess pro-inflammatory cytokines that are transported by blood and eventually breach synovial membranes covering joints on hands and feet, causing progressive damage of these joints.

In contrast, MS is an autoimmune disease that affects only the central nervous system, including the brain and spinal cord. The CNS has an immuno-privileged status in our body, as its blood-brain barrier protects it from our own immune system. In theory, the existence of BBB should prevent development of autoimmune diseases in the CNS, since it blocks penetration of pro-inflammatory cytokines from any immuno-competent organs, such as the spleen, intestines, liver, lungs, or kidneys. Conceivably, breaching the BBB in multiple sclerosis is analogous to breaching the synovial membrane in RA. This raises an interesting question: can VNS be similarly beneficial in MS?

We know that the beneficial effect of VNS in RA comes from its suppression of the spleen’s overactivity. VNS may be similarly involved in suppressing overactivity of other immuno-competent organs in our body, leading to a lower level of pro-inflammatory cytokines in the body, so fewer of them cross the BBB, even if it remains leaky.

An additional benefit may be that it prevents a vicious cycle, where pro-inflammatory cytokines further degrade the patency of BBB, which leads to even more cytokines crossing the BBB. Healing takes time, and VNS may provide that critical time for healing either the synovial membrane or the BBB by at least temporarily shielding them from new cytokine onslaughts. In the case of RA, SetPoint already has initial evidence that three-month-long VNS delivery was sufficient to heal the joints and achieve full remission in 33% of patients (two out of six).

Similar evidence for MS is not yet available and could be provided by SetPoint in a planned clinical study that is being co-designed with the FDA under its new TAP Pilot program. In the meantime, we have initial proof of efficacy for both reducing CNS inflammation and for increasing remyelination from studies using rodent models of experimental allergic encephalomyelitis and lysolecithin-induced demyelination performed by teams at Ghent University and SetPoint Medical.

From a financial point of view, the drug market for MS in the U.S. is estimated to be $10.5 billion in 2023 and according to a 2022 study, serves about 400,000 people in the U.S. The median annual price of generic and branded MS drugs per patient in the U.S. is estimated at $22,000 and $92,000, respectively.

As MS is presently uncurable and starts around 30 years of age, a typical patient may expect receiving drug therapy for 50 years or more. If SetPoint’s planned clinical study is successful, it may offer a cost-efficient alternative to drug therapy. An estimated lifetime of SetPoint’s implant battery is about 10 years (based on 500 recharges and weekly recharging). This corresponds to an annual cost of VNS therapy of about $3,000 based on a combined fee of $30,000 for the implant device and the implantation surgery. In relative terms, VNS therapy would be about seven times cheaper than generic drugs and 30 times cheaper than branded drugs, based on their current pricing.

Finally, from both clinical and financial points of view, SetPoint’s planned clinical study might provide additional benefits due to treating patients during an early relapsing-remitting phase of MS in contrast to their pivotal PMA clinical study for treating RA, where VNS therapy is delayed until a patient has failed at least one biologic therapy.