Alume Biosciences, Inc., a biotechnology company developing nerve-targeted pharmaceuticals for surgical and therapeutic use, today announced that it has received a "Study May Proceed" letter from the US Food and Drug Administration (FDA) related to its recently filed Investigational New Drug (IND) application for the use of ALM-488 in head and neck surgery.
ALM-488 is an intravenously administered peptide-dye conjugate for fluorescence highlighting of nerves during surgery. The IND was approved by the FDA Division of Medical Imaging and Radiation Medicine (DMIRM), which is responsible for drug products used in the image-based diagnosis and monitoring of diseases.
The Phase 1/2 trial of ALM-488 is a dose-escalation study in up to 36 patients undergoing head and neck surgery. Specific study cohorts will also examine ALM-488 dose timing ahead of surgery to determine effect on fluorescence nerve labeling. The primary objective of the Phase 1/2 trial is safety, and secondary objectives include determining the pharmacokinetics (PK) of ALM-488, observing efficacy as defined by dose at which optimal fluorescence signal is observed, and evaluation of the effect of dose timing relative to surgery on optimal fluorescence imaging characteristics. The study will proceed at three sites including the University California San Diego (UCSD), Stanford Medical Center and Harvard-Massachusetts Eye & Ear. Alume anticipates trial initiation in Q2 2020.
"As surgeons, we rely on our experience to identify nerves, but often they are buried or appear indistinguishable from adjacent non-nerve tissue. Our technology aims to improve the precision of surgery by making nerves 'glow' with fluorescence," said Alume's CEO and founder Quyen Nguyen, MD/PhD.
"Fluorescence is the GPS of surgery," said Dr. Santiago Horgan, Director for the Center of Fluorescence Guided Surgery, UCSD and Alume's Executive Clinical Advisory Board member. "This technology will be transformative for all types of surgery where nerves are potentially at risk. Alume's technology will improve the surgical safety and outcomes for patients worldwide."
"When I looked under the microscope, what I saw exceeded my expectations," said Ryan Orosco, MD, principal investigator of the UCSD clinical trial site. "The resolution was incredible."
"Seeing is believing… I think the most remarkable thing was when we were dissecting a nerve out, and it disappeared. We were not able to see it under white light, but then with the fluorescence you could see it very clearly through the muscle. You could immediately see the value of this technology," said Jeremy Richmon, MD, principal investigator at Harvard-Massachusetts Eye & Ear.
"It's a very exciting opportunity to learn more about how this nerve agent can improve our surgical confidence and improve operative times," said Eben Rosenthal, MD, Medical Director of the Stanford Cancer Center and principal investigator of the Stanford clinical trial site.
ALM-488 is a proprietary peptide-dye conjugate utilizing fluorescent excitation wavelength centered around 488nm. ALM-488 binds to the extracellular matrix of nerves, allowing real time nerve illumination during surgery. ALM-488 is expected to have broad surgical application due to unique characteristics of binding that are independent of myelin. This allows ALM-488 to highlight multiple types of nerves including motor, sensory, autonomic and degenerated nerves important during reconstructive procedures. Human autonomic nerves in the neurovascular bundle around the prostate gland, important for continence and erectile function and known to be poorly myelinated, label well with ALM-488 in preclinical tests. Surgeries where nerves are potentially at risk include procedures in the skull base, head and neck, spine, and nerve sparing prostatectomy. In vivo preclinical studies also indicate that ALM-488 has adequate pharmacokinetic characteristics to support clinical utility for the labelling of ureters in urology, gynecology and lower abdominal surgical indications.
For more information please visit us at www.alumebiosciences.com.