A U.S.- Chile collaboration could bring a long-acting local anesthetic to surgical patients managing pain.
Working at a licensing office at an academic medical center, we are accustomed to marketing early-stage technologies. Rarely do we have the opportunity to license a technology with clinical data, and even a clinical grade compound that we have access to through a partnership with a manufacturing facility. But we are in this fortunate position right now, with a mature technology that has the potential to change the standard of care for anesthesia, by virtue of collaboration with a Chilean company, Proteus SA. Children’s and Proteus are looking for a commercial partner who is ready to take this asset through late-stage clinical trials and to market.
Charles Berde, MD, PhD, Chief of the Division of Pain Medicine, has been seeking better alternatives for pain management for several decades, based on his experiences treating pediatric patients here at Children’s. Worldwide, tens of millions of patients undergo surgical procedures requiring local anesthesia each year. The current market for local anesthetics is estimated at over $1 Billion a year. Current local anesthetics and analgesics based on opioids have a short duration of action (8 hours or less), leaving patients to cope with postoperative pain, and cause substantial side effects, such as cardiac adverse events, nausea, sedation, shallow breathing, confusion, and itchiness, seizures and refractory toxicity. These side effects often delay recovery and can result in prolonged hospitalization.
Thirteen years ago, Dr. Berde, Daniel Kohane, MD, PhD, a clinician-researcher in Critical Care Medicine here at Children’s, Gary Strichartz, PhD at Brigham and Women’s Hospital and Robert Langer, ScD at MIT, found that site 1 sodium channel blockers, specifically, tetrodotoxin, a molecule that is derived from puffer fish, could be the key to overcoming the drawbacks in the standard of care treatments. They showed that by combining site 1 sodium channel blockers with local anesthetics, a nerve blockade can be prolonged from 8 hours to periods of two to four days in animals with minimal local or systemic side effects. This could lead to a dramatic change in management of post-operative pain, as well as acute and chronic pain.
Site 1 sodium channel blockers bind to the pores of the voltage-gated, fast sodium channels in nerve cell membranes and block action potentials. These channel blockers have advantages over existing analgesics and anesthetics because they do not cause the effects mentioned above and also, importantly, do not induce a feeling of euphoria, thereby removing the risk of addiction and dependence.
3 years ago, the Chilean company Proteus was studying the use of a different site 1 sodium channel blocker, saxotoxin (STX), as a long acting local anesthetic. Proteus was able to overcome a major obstacle to bringing a site 1 sodium channel blocker to market: the synthesis and purification of the chemical compound. Chile’s shore line frequently faces problems with Red Tide, where the harmful toxin released by the algae is a type of STX. Proteus learned from this problem and used its expertise in STX chemistry to develop novel culture methods for freshwater microalgae, perfecting techniques for extraction and purification of the active compound, which led to a new STX formulation known as NeoSTX.
The Proteus team took NeoSTX into clinical studies that involved 137 patients having laparoscopic removal of their gall bladders in Chile. As reported in the March-April issue of Regional Anesthesia and Pain Medicine, significantly fewer patients randomized to receive NeoSTX reported severe postoperative pain at the incision site at both 12 hours (4 vs. 18 percent) and 24 hours (6 vs. 16 percent). Significantly more NeoSTX-treated patients had complete absence of pain at 12 hours, both at rest (88 vs. 69 percent) and with movement (80 vs. 60 percent). Patients in the NeoSTX group reported a full functional recovery approximately 2 days earlier. No serious adverse reactions occurred in either group.
Children’s and Proteus are now working together to further the development of NeoSTX for pain. As part of the collaboration, Children’s investigators will carry out additional preclinical work and early-stage clinical trials, while Proteus will provide the compound and additional expertise and early-stage clinical data.
Boston Children's is poised to begin clinical trials in the U.S. this year to determine optimal doses that block pain while avoiding toxicity. Groups of adult volunteers will receive NeoSTX injections under the skin in gradually increasing doses. Although NeoSTX has appeared very safe in over 400 patients in clinical trials so far, the upcoming study will more precisely determine the margin of safety.