Boston Children's Hospital has received Investigational New Drug (IND) approval from the US Food and Drug Administration (FDA) for neosaxitoxin, a new local anesthetic derived from cyanobacteria being developed in partnership with Proteus SA, of Santiago, Chile. With the IND approval in hand, the hospital has launched a Phase I clinical study in healthy volunteers.
"The FDA is satisfied that we have collected enough preclinical toxicology data to move forward with the trial," says Charles Berde, MD, PhD, chief of the Division of Pain Medicine in Boston Children's Hospital's Department of Anesthesiology and lead investigator in the trial. "With this trial, we aim to determine the correct dose, establish safety and measure how neosaxitoxin clears from the body."
Neosaxitoxin is a site 1 sodium channel blocker, part of a larger class of emerging anesthetics based on molecules derived from aquatic organisms, including cyanobacteria. Often referred to as blue-green algae, cyanobacteria have been the subject of significant interest in recent years with respect to biotechnology applications.
Neosaxitoxin's clinical potential as a local anesthetic is the result of two intertwined research efforts: one by Berde and his collaborator Daniel Kohane, MD, PhD, on site 1 sodium channel blockers; and the other by Proteus' past scientific director Alberto Rodríguez-Navarro, MD.
In prior clinical testing carried out in Chile, neosaxitoxin was shown to provide local anesthesia for more than 24 hours following laparoscopic gall bladder removal. The current trial will provide more refined dose escalation and safety data in line with FDA standards, using neosaxitoxin produced by Proteus through an inexpensive, proprietary and GLP-compliant production and purification methodology.
Berde and his collaborators believe that neosaxitoxin might overcome limitations of the methods currently available for local postoperative pain control while providing prolonged pain management. Further, this enhanced effect can be accomplished absent the local or system toxicity associated with other local anesthetics. For instance, current local anesthetics, such as bupivacaine, act for fewer than eight hours; when they wear off, patients are generally prescribed opioid analgesics. These drugs can cause substantial side effects, including nausea, sedation, shallow breathing, sleepiness, constipation and itching, all of which can delay recovery or prolong hospitalization. In addition, opioids come with a significant addiction risk.
"We are very excited to see Boston Children's launch this US Phase I trial, an important step towards applying to the Food and Drug Administration for approval of neosaxitoxin," said Luis Novoa, chief executive officer of Proteus SA. "We are confident about the progress Proteus and the hospital have made thus far together in the development of neosaxitoxin. We look forward to the outcomes of the trial, which we think will add significantly to the positive outcomes we saw in clinical studies conducted here in Chile."
"This trial represents one of those rare cases where a single academic medical institution has been involved in the development of a drug product at every step from inception to clinical testing," says Erik Halvorsen, PhD, executive director of the Technology and Innovation Development Office (TIDO) at Boston Children's. "The hospital has committed significant resources to the preclinical and clinical development neosaxitoxin, and we share the enthusiasm of our collaborators at Proteus at achieving this milestone."