MIS416 explained

MIS416 is an experimental drug developed by Innate Immunotherapeutics which underwent clinical trials to treat secondary progressive multiple sclerosis. It is derived from the bacteria that causes acne and targets myeloid cells through TLR9 and NOD2.[1] [2] [3] [4] In one of its first rounds of clinical trials, the drug was shown to be "safe and well tolerated", with 80% of secondary-progressive multiple sclerosis patients exhibiting more than 30% improvement in at least one area of their MS status. However, Phase II clinical trials were unable to prove that the drug provided a benefit to patients. It is also being researched as a potential treatment for cancer.

Development

MIS416 is a microparticle derived from the cytoskeleton of P. acnes, a species of bacteria present on the skin of most adults that causes acne.[5]

MIS416 was originally developed as a vaccine adjuvant, a component of vaccines that helps to activate an immune response against the vaccine target. Bacteria-derived microparticles have several advantages over traditional adjuvants related both to their size and biological properties.[6] [7]

Because MIS416 is engulfed by immune cells, it is being investigated as an immunotherapy-based treatment for solid tumors.

The drug was used to treat multiple sclerosis under a compassionate use law in New Zealand before clinical trials began.[6] It is administered as an intravenous infusion. In 2017, clinical trials in people with secondary progressive multiple sclerosis failed to meet the primary endpoint of slowed progression of the disease.[2]

Phase II trial and aftermath

On June 22, 2017, Innate Immunotherapeutics announced that clinical trials undertaken to evaluate the efficacy of MIS416 in managing secondary progressive multiple sclerosis (SPMS) had "failed to show any clinically meaningful benefit or statistical significance".[8] As a result, the company's stock dropped by 92 percent[9] and crashed on the Australian Securities Exchange.[8]

US Congressman Chris Collins, a member of the company's board of directors and 17-percent stock holder, was subsequently indicted on charges of insider trading in connection with the poor clinical trial results.[9] Collins had allegedly obtained word from the company about the results and informed his son, Cameron Collins, who immediately sold his US stock. Cameron allegedly tipped off shareholder Stephen Zarsky, who informed three others, thus preventing a total loss of $768,000 in stocks. Zarsky was indicted together with Collins and his son.[9]

Notes and References

  1. October 2013. Innate Immunotherapeutics: Acne Offers Real Hope for MS Treatment. Australasian Biotechnology. 23. 3. 55. 1036-7128.
  2. Web site: Drug Profile: MIS 416 . adisinsight.springer.com . 27 June 2018. 29 August 2018.
  3. Web site: Results Announced from Phase 2 Trial of MIS416 . 27 June 2017. National Multiple Sclerosis Society.
  4. Web site: Safety and Efficacy Study of MIS416 to Treat Secondary Progressive Multiple Sclerosis . 28 August 2014. 29 August 2018. United States National Library of Medicine.
  5. Brüggemann . Holger . Henne . Anke . Hoster . Frank . Liesegang . Heiko . Wiezer . Arnim . Strittmatter . Axel . Hujer . Sandra . Dürre . Peter . Gottschalk . Gerhard . The Complete Genome Sequence of Propionibacterium Acnes, a Commensal of Human Skin . Science . 30 July 2004 . 305 . 5684 . 671–673 . 10.1126/science.1100330 . 15286373 . 2004Sci...305..671B . 26252335 . en . 0036-8075.
  6. Shirani . Afsaneh . Okuda . Darin T. . Stüve . Olaf . Therapeutic Advances and Future Prospects in Progressive Forms of Multiple Sclerosis . Neurotherapeutics . 2016 . 13 . 1 . 58–69 . 10.1007/s13311-015-0409-z . 26729332 . 1933-7213. 4720678 .
  7. MIS416, a non-toxic microparticle adjuvant derived from Propionibacterium acnes comprising immunostimulatory muramyl dipeptide and bacterial DNA promotes cross-priming and Th1 immunity . Vaccine . 10 January 2011 . 29 . 3 . 545–557 . 10.1016/j.vaccine.2010.10.040 . 21034827 . en . 0264-410X. Girvan . Rebecca C. . Knight . Deborah A. . o'Loughlin . Chris J. . Hayman . Colin M. . Hermans . Ian F. . Webster . Gill A. .
  8. Web site: Innate becomes the latest loser in MS . Lisa . LaMotta . June 27, 2017 . August 8, 2018 . BioPharma Dive.
  9. Web site: New York Congressman Chris Collins indicted on insider trading charges. 8 August 2018. CBS News. 29 August 2018.