Chemistry:LGD-4033

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LGD-4033
LGD-4033.svg
Clinical data
Other namesVK5211; Ligandrol
Routes of
administration		By mouth
ATC code
  • none
Legal status
Legal status
Pharmacokinetic data
Elimination half-life24-36 hours [1]
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC14H12F6N2O
Molar mass338.253 g·mol−1
3D model (JSmol)

LGD-4033 (VK5211, Ligandrol)[2] is an investigational selective androgen receptor modulator (SARM) for treatment of conditions such as muscle wasting and osteoporosis, discovered by Ligand Pharmaceuticals and currently under development by Viking Therapeutics.[3][4]

Commercial environment

Viking Therapeutics does not currently manufacture any pharmaceutical products, but is developing several products to treat metabolic and endocrine disorders. Thus, the company relies upon investments from stockholders and business partners. The company completed its Initial Public Offering in the 2nd quarter of Fiscal Year 2015, generating $22.3M in net proceeds.[5] Viking Therapeutics assumed the largest expense in 2014 from cited Research and Development costs ($21.2M), which may be related to purchase of required equipment and facilities to develop the drug candidates licensed by Ligand Pharmaceuticals in that year, including LGD-4033.[5]

Financial risks of development

Viking Therapeutics is yet to bring a drug to market. If one or several of their drug candidates does not pass clinical trials before one is successfully brought to market, then a significant amount of stockholders would likely sell their stocks, seriously reducing revenue and capability to continue development of LGD-4033. Additionally, as noted in the Form 10-Q submitted on 10 November 2016, Viking currently relies heavily upon licensed technologies by Ligand Pharmaceutics. If Viking Therapeutics were to lose this license, then its operating capability would be severely impacted.[6]

Other commercial aspects

Ligand Pharmaceutics has disclosed that its royalty fee incurred upon Viking Therapeutics for production and sale of LGD-4033 would be 7.25-9.25% of the product revenue.[7]

Another promising drug candidate, VK2809, is expected to drive a major shift in the market cap of Viking Therapeutics and its share of the market for TRβ agonists, which is currently dominated by Madrigal Pharmaceuticals.[8] This would improve the company portfolio as a whole, and would allow for greater capitalization upon the potential success of LGD-4033.

Intellectual property

Ligand Pharmaceuticals has patents filed for the manufacture and therapeutic use of certain compounds occupying several stated chemical structures, which are intended for use as selective androgen receptor modulators. The patent is filed under the following designations: US8519158 B2, US8865918, US9359285, US20070254875, US20140005186, US20150099720, and WO2005090282A1. The patents will expire on March 12, 2025. These patents effectively protect any future capitalization upon LGD-4033 in the market by Viking and Ligand through their licensing agreement.[9]

Regulatory information

LGD-4033 is currently an Investigational New Drug.

Pre-clinical

Oral administration of the drug to cynomolgus monkeys at daily doses varying from 0 to 75 mg/kg over 13 weeks demonstrated significant body weight gain in both males and females. After 48 days, the 75 mg/kg dose testing was halted due to toxicity concerns, but this did not negatively impact development as the dose is significantly higher than those being utilized in the Phase 2 clinical trial.[10]

Clinical trials

In a Phase 1 clinical trial of 76 adult male humans in which the dose size was varied, a dose-dependent increase in lean body mass was observed with no significant adverse events over 21 days.[2]

The Phase 2 clinical trial, initiated on 3 November 2016, consists of 120 patients recovering from hip fracture surgery. The randomized study participants will receive either a placebo or varying dose sizes of LGD-4033 over a period of 12 weeks, with improved lean body mass as the primary endpoint. Other endpoints include satisfactory results in terms of quality of life, safety, and pharmacokinetics.[11]

Illicit use

Though not an approved drug, LGD-4033 has been sold on the black market[12][13] and has been found in drug testing samples of some athletes.[14]

In 2015, the quarterback of the Florida Gators, Will Grier, was suspended for testing positive for LGD-4033, a claim that the University of Florida denies.[15] In 2017, Joakim Noah was banned for twenty games by the NBA for testing positive for LGD-4033.[16]

References

  1. ↑ "The safety, pharmacokinetics, and effects of LGD-4033, a novel nonsteroidal oral, selective androgen receptor modulator, in healthy young men.". J Gerontol a Biol Sci Med Sci 68 (1): 87–95. Jan 2013. doi:10.1093/gerona/gls078. PMID 22459616. 
  2. ↑ 2.0 2.1 Basaria, S., L. Collins, E. L. Dillon, K. Orwoll, T. W. Storer, R. Miciek, J. Ulloor, A. Zhang, R. Eder, H. Zientek, G. Gordon, S. Kazmi, M. Sheffield-Moore, and S. Bhasin. "The Safety, Pharmacokinetics, and Effects of LGD-4033, a Novel Nonsteroidal Oral, Selective Androgen Receptor Modulator, in Healthy Young Men." The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 68.1 (2012): 87-95. Web. 21 Nov. 2016.
  3. ↑ "Ligand Presents New Preclinical Data on its Lead SARM Molecule LGD-4033 at the Gerontological Society of America Annual Meeting" (Press release). San Diego: Ligand Pharmaceuticals. November 20, 2009. Retrieved November 23, 2014.
  4. ↑ Viking Signs Broad Licensing Deal With Ligand Pharmaceuticals for Rights to Five Novel Therapeutic Programs
  5. ↑ 5.0 5.1 Lian, Brian, Ph.D. "Q2 2015." Viking Therapeutics InvestorRoom. Viking Therapeutics, Inc., 3 Aug. 2015. Web. 21 Nov. 2016.
  6. ↑ Lian, Brian, Ph.D. “Form 10-Q: Viking Therapeutics, Inc. –VKTX.” www.vikingtherapeutics.com (2016).Web. 21 November 2016.
  7. ↑ "Royalty Table :: Ligand Pharmaceuticals, Inc. (LGND)." Royalty Table :: Ligand Pharmaceuticals, Inc. (LGND). Ligand Pharmaceuticals, Inc., 21 Nov. 2016. Web. 21 Nov. 2016.
  8. ↑ Bautz, David, PhD. "VKTX: Phase 2 Study of VK5211 for Hip Fracture Ongoing; Phase 2 Study of VK2809 for Hypercholersterolemia to Commence in Mid-2016." Yahoo Finance - Business Finance, Stock Market, Quotes, News. Yahoo, Inc., 16 May 2016. Web. 21 Nov. 2016.
  9. ↑ Zhi, Lin, Robert I. Higuchi, Cornelis Arjan Van Oeveren, Thomas Lot Stevens Lau, and Ligand Pharmaceuticals Incorporated. Androgen Receptor Modulator Compounds and Methods. Ligand Pharmaceuticals Incorporated, assignee. Patent US 8519158 B2. 11 Mar. 2005. Print.
  10. ↑ Bautz, David, PhD. "VKTX: Additional Preclinical Data Shows Robust and Durable Weight Gain for VK5211-Treated Primates." Yahoo. Yahoo, Inc., 8 Dec. 2015. Web. 21 Nov. 2016.
  11. ↑ "Viking Therapeutics Initiates Phase 2 Trial of VK5211 in Patients Recovering From Hip Fracture." FierceBiotech. Questex LLC, 03 Nov. 2015. Web. 21 Nov. 2016.
  12. ↑ Geldof, Lore; Pozo, Oscar J.; Lootens, Leen; Morthier, Wouter; Van Eenoo, Peter; Deventer, Koen (2017). "In vitro metabolism study of a black market product containing SARM LGD-4033". Drug Testing and Analysis 9 (2): 168–178. doi:10.1002/dta.1930. PMID 26767942. 
  13. ↑ Krug, Oliver; Thomas, Andreas; Walpurgis, Katja; Piper, Thomas; Sigmund, Gerd; Schänzer, Wilhelm; Laussmann, Tim; Thevis, Mario (2014). "Identification of black market products and potential doping agents in Germany 2010–2013". European Journal of Clinical Pharmacology 70 (11): 1303–1311. doi:10.1007/s00228-014-1743-5. PMID 25168622. 
  14. ↑ Cox, Holly D.; Eichner, Daniel (2017). "Detection of LGD-4033 and its metabolites in athlete urine samples". Drug Testing and Analysis 9 (1): 127–134. doi:10.1002/dta.1986. PMID 27168428. 
  15. ↑ Trahan, Kevin (12 October 2015). "Florida starting QB Will Grier suspended for at least 2015 after taking banned substance". SB Nation. Retrieved 20 October 2015.
  16. ↑ "NBA bans Joakim Noah 20 games for drug violation". Fox Sports. March 25, 2017. https://www.foxsports.com/nba/story/nba-bans-joakim-noah-20-games-for-drug-violation-032517. 




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