Data from a preclinical study presented last week at the 2016 AAPS National Meeting demonstrated significant data concerning the effects of a cannabinoid-based drug in lowering the effect of Intraocular Pressure (IOP).
The abstract, “Effect of single versus multiple day regimen of Δ9 -THC-valine-hemisuccinate (THCVHS) on the intra-ocular pressure (IOP) lowering activity in normotensive rabbits” (abstract # 30W0830), reports data comparing the prodrug of tetrahydrocannabinol (THCVHS) also known as NB1111 (Nemus Bioscience), to established glaucoma therapies of Pilocarpine and Timolol, as well as standard Δ9 -THC in both emulsion and solid lipid nanoparticle (SLN) eye drops. All studies were conducted in a normal, non-glaucomatous eye. The goals of the studies were to examine penetration and concentration of NB1111 in ocular tissues responsible for IOP regulation and to correlate that concentration to measurement of IOP. Additionally, the studies examined the effect on drug half-life by encapsulating NB1111 in a SLN with single- and multiple-day dosing for up to five days.
The data revealed:
- NB1111 lowered IOP in a normal eye in a statistically significant manner with peak IOP decline of 32% versus 16% for Pilocarpine and 23% for Timolol (p< 0.05); prior experiments in a glaucomatous eye exhibited a 45% IOP reduction for NB1111
- The experiments demonstrated that increased drug concentration of NB1111 in the ciliary body and retina/choroid plexus was correlated with a decline in IOP; these ocular organs help regulate IOP
- Use of Δ9 – THC (parent molecule, non-prodrug), whether formulated in an emulsion or SLN eye drop solution, resulted in no significant tissue concentration nor decline in IOP
- Formulation of NB1111 into an SLN produced a duration of activity that could be consistent with twice daily eye drop dosing in humans and successfully transported the drug into both the anterior and posterior compartments of the eye and was highly significant compared to both approved comparator drugs (p<0.001)
- No safety issues were noted with the administration of NB1111 over five days dosing
- No free THC was detected in the peripheral circulation of the test animals after repeated dosing NB1111 using an assay with nanogram detection sensitivity
“These findings are critical to our understanding on how this novel prodrug of THC can reduce IOP so effectively,” stated Soumyajit Majumdar, PhD, Professor of Pharmaceutics and Drug Delivery and Associate Dean for Research in the School of Pharmacy at the university and lead scientist of the ophthalmic studies of NB1111. “As important as the ocular findings were in these studies, we were also pleased to see that the plasma THC levels in these animals, even those undergoing repeated ocular dosing, did not have detectable levels of THC. This is a key safety finding for this drug.”
Dr. Mahmoud ElSohly, professor at the National Center for Natural Products Research at the University of Mississippi, commented: “Multiple experiments, including previously reported data, have clearly demonstrated a causal relationship between the drug’s tissue concentration and IOP lowering in both normal and glaucomatous eyes. This unique prodrug technology has enhanced treatment concentrations in the eye and could signal a new therapeutic class for the management of glaucoma.”
“NB1111 has performed above expectations in the ability to lower IOP in these animal models. We want to further explore the neuroprotective effects of cannabinoids upon the optic nerve and move the ophthalmology program into human testing. I am also happy to report that our colleagues at the University of Mississippi have been able to develop an early ocular formulation of our CBD analogue, and in doing so, expands our ocular program into a full-fledged ophthalmology platform that could address multiple eye diseases beyond glaucoma, including diseases of the retina,” noted Brian Murphy, MD, MBA, Nemus CEO and Chief Medical Officer.
A link to the abstract on the AAPS website can be found at https://annual.aapsmeeting.org/poster/member/66948.