Dirucotide

from Wikipedia, the free encyclopedia
Dirucotide
Dirucotide
Mass / length primary structure 2013.29 g mol −1
Identifier
External IDs

Dirucotide , also known as MBP8298 , is an experimental immunomodulatory drug that has been tested in the treatment of relapsing and chronic forms of multiple sclerosis (MS). Dirucotide is a synthetic peptide made up of amino acids 82–98 from myelin basic protein ("MBP").

Working principle

As a mimicked myeline protein , Dirucotid is supposed to direct and gradually reduce the misdirected immune reaction against the protective covering of the nerve pathways (myelin sheath) in MS, thus restoring immune tolerance .

The main point of attack of the MS-relevant B and T cells is encoded in the sequence 82 to 98 of the synthetic MBP. The aim is to neutralize these B- and T-cells and also reduce the release of autoaggressive antibodies.

It is believed that only patients who carry certain gene variants ( HLA DR2 / DR4 haplotype ) benefit from treatment with Dirucotide. This applies to around 65–75% of people with MS. In the general population, the probability is only between 20 and 30%.

Clinical development

Dirucotide was discovered at the Canadian University of Alberta in Edmonton . The drug was then out- licensed to the Edmonton-based company BioMS Medical . The US company Lilly has been involved in the development of Dirucotid since the end of 2008 .

The drug was double-blinded in a smaller Phase II study in 32 patients with progressive MS for two years . No difference to placebo could be shown in the overall study . However, when the analysis was restricted to the 20 patients who are carriers of the HLA haplotype DR2 / DR4, there was a benefit from treatment with Dirucotide. A follow-up of these 20 patients over a further five years indicated that the median time to progression of MS disability could be increased from 18 to 78 months after treatment with Dirucotide.

In 2005, a phase II / III study on the efficacy of Dirucotide in secondary progressive MS began and in 2006 a phase II study in relapsing MS .

In the studies, Dirucotide is injected intravenously every six months .

The active ingredient was well tolerated in the published study. There was only redness and burning at the injection site.

After the primary and some secondary endpoints were not achieved in a phase III study on SPMS, all studies on Dirucotide were discontinued.

Web links

Individual evidence

  1. ↑ KG Warren, I. Catz, KW Wucherpfennig: Tolerance induction to myelin basic protein by intravenous synthetic peptides containing epitope P85 VVHFFKNIVTP96 in chronic progressive multiple sclerosis. In: J Neurol Sci. 152, 1997, pp. 31-38. PMID 9395124
  2. ↑ K. Riddell: BioMS May Give Lilly $ 5 trillion Cure for Drug Expiring patent. bloomberg.com, December 26, 2008; Retrieved December 30, 2008.
  3. ↑ a b K. G. Warren, I. Catz, LZ Ferenczi, MJ Krantz: Intravenous synthetic peptide MBP8298 delayed disease progression in an HLA Class II-defined cohort of patients with progressive multiple sclerosis: results of a 24-month double-blind placebo-controlled clinical trial and 5 years of follow-up treatment. In: Eur J Neurol. 13, 2006, pp. 887-895. PMID 16879301
  4. ↑ BioMS scrap MS drug after trial fails