Research and Markets: Receptos' RPC1063 for multiple sclerosis

DUBLIN--()--Research and Markets ( has announced the addition of the "Receptos' RPC1063 for multiple sclerosis" report to their offering.

Sphingosine-1 phosphate (S1P) is a bioactive sphingolipid that promotes lymphocyte survival, cell migration, and inflammation. S1P agonism was validated as a therapeutic approach in multiple sclerosis (MS) with the approval of fingolimod (Novartis' Gilenya), a structural analogue of S1P. Fingolimod, an oral non-specific S1P receptor family modulator reduces relapse rates and disability progression in MS, but it has many side effects. The drug has been successful as the first oral disease-modifying drug (DMD) introduced into the MS armamentarium with $1.03 billion in US and $1.9 billion in worldwide sales in 2013.

The S1P1 receptor subtype appears to drive fingolimod's clinical benefit (via the inhibition of lymphocyte trafficking), while other receptor subtypes mainly S1P3- account for most of its toxicities. Among safety concerns, cardiac effects, macular edema, and melanoma rates have been particularly concerning.

Next generation, selective S1P agonists or modulators are regarded as promising strategies to improve risk/benefit over fingolimod treatment.

Receptos is developing RPC1063, pinning its hopes on the hypothesis that a selective S1P1 receptor (S1P1R) agonist, RPC1063, will have activity similar to fingolimod's but with better safety. Other oral, selective S1P modulators in development are:

  • Siponimod (Novartis) - S1P1 and S1P5
  • Ponesimod (Actelion) - S1P1
  • ONO-4641 (Merck Serono) - S1P1 and S1P5
  • MT-1303 (Mitsubishi Tanabe) - S1P agonist

Key Topics Covered:

Multiple Sclerosis

  • Current treatments

Sphingosine-1-Phosphate Receptor Modulators

  • Novartis' fingolimod (Gilenya) - the relevant precedent
  • Fingolimod's Efficacy in Registration Trials
  • Safety to Date

Receptos' RPC1063: Second Generation S1PR Modulator

  • Preclinical Studies
  • Phase I trial in healthy volunteers
  • QT prolongation study
  • Phase II/III (RADIANCE trial)

Other Selective S1PR Agonists Under Evaluation

  • Siponimod/BAF312 - (Novartis)
  • Ponesimod (Actelion)
  • ONO-4641 (Merck Serono)
  • MT-1303 (Mitsubishi Tanabe)

Clinical and Regulatory Discussion

  • There is rationale supporting a more specific S1P1 agent
  • Does S1P5 activity mediate some benefit with fingolimod?
  • Lymphopenia as a biomarker of activity in MS
  • Lessons for Receptos
  • Regulatory Comments
  • Clinical Trial Design Issues

Overview of the Market for MS Therapies

Summary Opinion

Companies Mentioned:

  • Actelion
  • Biogen-Idec
  • Merck Serono
  • Mitsubishi Tanabe
  • Novartis
  • Receptos
  • Sanofi
  • Teva

For more information visit


Research and Markets
Laura Wood, Senior Manager
U.S. Fax: 646-607-1907
Fax (outside U.S.): +353-1-481-1716
Sector: Pharmaceuticals


Research and Markets
Laura Wood, Senior Manager
U.S. Fax: 646-607-1907
Fax (outside U.S.): +353-1-481-1716
Sector: Pharmaceuticals