Potential Utility of LAT8881

Neuropathic Pain

  • Potential Utility of LAT8881 in Neuropathic Pain
  • Potential Utility of LAT8881 in Osteoarthritis
  • Target Osteoarthritis Market
  • References

Chronic neuropathic pain remains a clinical area with high unmet need due to several factors. Including a relative lack of investment in new pain drugs by biotech and pharma; Clinical failures/delays due to safety issues in humans (anti-NGF) or failure to demonstrate efficacy in trials with the overall lower success rate for pain drugs transitioning from Phase 1 to Approval of 2% compared to average for all drugs of 9.6%; and  the highly publicized safety and misuse concerns with opioids and more recently with gabapentinoids.

The extent of the opioid and gabapentinoid crises is outlined by the following statistics:

  • 80% of heroin users report misusing prescription opioids prior to heroin (NIH, 2019)
  • 11.1 million Americans are estimated to have past-year misuse/abuse of prescription opioids (FDA, 2019)
  • 130+ people a day die from opioid-related drug overdoses in the U.S. (NIH, 2019)
  • The total “economic burden” of prescription opioid misuse alone in the US is estimated to be USD$78.5 Billion in healthcare, law enforcement and lost productivity (NIH, 2017)
  • In 2017, 47,600 Americans died because of opioid overdose (Centers for Disease Control and Prevention, 2018)
  • In UK  from 2006-2016 prescriptions of gabapentin have risen fivefold, from 1 million to 6.5 million, while those for pregabalin, have risen tenfold (Waters, 2017)
  • GABA drugs are also being prescribed for pain they’re not actually licensed to treat, such as arthritis or lower back pain (Waters, 2017)
  • gabapentin and pregabalin use in non-neuropathic pain disorders indicates they are less effective than several other licensed non-opioid analgesics (Morrison, Sandilands & Webb, 2017)
  • There is a significant illicit market for these controlled drugs, which are known to ‘potentiate’ or enhance the effects of opioids (Peckham, Ananickal & Sclar,  2018)

 

Figure 1 U.S drug overdose deaths involving any opioid, 1999-2017 (Center for Disease Control and Prevention, 2018)National drug overdose deaths

The Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment (SUPPORT) for Patients and Communities Act – October 2018 is aimed at addressing the opioid overdose epidemic in the United States. It includes provisions to educate the population about addiction medicine, standardize the delivery of addiction medicine and cover addiction medicine in a way that facilitates the delivery of coordinated and comprehensive treatment. It also outlines the need for a safe, effective, non-addictive treatments to manage chronic pain (FDA, 2019).

Policy change in the U.S. raises the possibility of collaborative research studies with the NIH through the HEAL initiative, and FDA expedited pathways. Lateral could pursue:

  • various partnerships and collaboration opportunities with the NIH
  • NIH grant opportunities
  • Breakthrough Therapy Designation with the FDA
  • FDA Accelerated Approval
  • FDA Fast Track
  • FDA Priority Review

In 2015 our collaborator published:

Effect of Intra-articular Injection of AOD9604 with or without Hyaluronic Acid in Rabbit Osteoarthritis Model – Kwon and Park (2015)

In 2010 Dr Kwon and co-workers published a paper in the Journal of Korean Medical Science (2010; 25: 776-780) titled “Additive Effects of Intra-articular Injection of Growth Hormone and Hyaluronic Acid in Rabbit Model of Collagenase-induced Osteoarthritis”. In that study the co-injection of intra-articular HA and human Growth Hormone (hGH) was more effective than HA alone in the osteoarthritis model in terms of duration and severity of lameness, lower macroscopic scores of cartilage damage and histopathological scores of cartilage damage.  In that study HA alone proved to be more effective than control (saline) on the same measures.

Dr Kwon was asked to collaborate on a similarly designed study to evaluate the effect of LAT8881 in the University Medical Center’s model.

In commenting on his study findings Dr Kwon MD, PhD said “These results are exciting because they provide early stage evidence in a rabbit model that LAT8881 may help to repair OA damaged tissue.  LAT8881 appears to have retained the same beneficial effects as hGH in our rabbit model of collagenase-induced OA.” This evidence gives Lateral Pharma increased confidence that LAT8881 can be further developed to become an effective treatment for OA in both humans and companion animals.

Potential Utility of LAT8881 in Osteoarthritis This encouraging in-vivo efficacy data when combined with the highly favourable safety profile of LAT8881, proven in formal pre-clinical toxicology studies and six human clinical trials, provides strong rationale for use of the peptide to treat OA.

LAT8881 could offer further advantages in that it can be dosed in multiple forms including oral, transdermal, injection and intra-articular.

The potential uses outlined above target support in conditions, trauma and injuries with very large markets and where there are limited or no adequate treatment options.

For instance in the case of Osteoarthritis, this is the most common joint disease with 12.1% of US adults showing symptoms in the knee and obesity being associated with a 3.5 fold prevalence of OA in US adults between 60-64 years of age. (Medtrack database).

The majority of treatments only address the pain associated with OA. Across the seven major markets of the U.S, France, Germany, Italy, Spain, the U.K and Japan the osteoarthritis market was worth $3.25B in 2014 and expected to grow at a Compound Annual Growth Rate of 17.8%  to reach $10.49B by 2024 (GlobalData, 2016)

Centers for Disease Control and Prevention. (2018). “National Drug Overdose Deaths Number      Among All Ages, by Gender, 1999-2017.” National Institute of Health. Retrieved on the           13th of May 2019 from https://www.drugabuse.gov/related-topics/trends-statistics/overdose   death-rates

 

Gottlieb, S. (2018). “Statement by FDA Commissioner Scott Gottlieb, M.D., on the agency’s           ongoing work to forcefully address the opioid crisis.” U.S. Food & Drug Administration        (FDA). Retrieved on the 13th of May 2019 from https://www.fda.gov/news-events/press      announcements/statement-fda-commissioner-scott-gottlieb-md-agencys-ongoing-work         forcefully-address-opioid-crisis

 

Morrison, E.E., Sandilands, E.A., & Webb, D.J. (2017). “Gabapentin and pregabalin: do the benefits outweigh the harms?” J R Coll Physicians Edinb, 47(4), 310-313. doi:10.4997/JRCPE.2017.402

 

National Instutute on Drug Abuse. (2019). “Opioid Overdose Crisis.” National Institute of Health.  Retrieved on the 13th of May 2019 from https://www.drugabuse.gov/drugs abuse/opioids/opioid-overdose-crisis

 

Peckham, A.M., Ananickal, M.J., & Sclar, D.A. (2018). “Gabapentin use, abuse, and the US opioid epidemic: the case for reclassification as a controlled substance and the need for     pharmacovigilance.” Risk Manag Healthc Policy, 11, 109-116. doi:10.2147/RMHP.S168504

 

Thomas, D., & Wessel, D. (2018). “Volume II: Pain and Addiction Therapeutics.” The State of         Innovation in Highly Prevalent Chronic Diseases. Biotechnology Innovation Organization. Retrieved on the 13th May 2019 from https://www.bio.org/sites/default/files/BIO_HPCP_Series-Pain_Addiction_2018-02-08.pdf

 

Waters, J. (2017). “The crippling toll of the new Valium that’s ruining the lives of MILLIONS: Rapid            rise in prescriptions for GABA drugs is worrying experts.” Daily Mail Australia. Retrieved on 13 May 2019 from https://www.dailymail.co.uk/health/article-5102355/Crippling-toll-new     valium-ruining-lives-MILLIONS.html