Last updated: 23 Jun 2014

ONO-4641

Summary

Trade name:

Ceralifimod

(7)

Merck KGaA Reaches Mutual Agreement with Ono Pharmaceutical to Terminate the License Agreement on Ceralifimod (ONO-4641)

Merck KGaA, 17 Jun 2014

Accessed on 23 Jun 2014 from http://news.emdgroup.com/N/0/CA6B3B25E9032894C1257CFA001FE133/$File/OnoEMD.pdf.

Class:

Immunomodulator

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Target:

Sphingosine 1-phosphate receptor

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Status for MS:

Phase II

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Administration:

Oral

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Commercial:

Discovered by Ono Pharmaceutical Co.

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Developed by Ono Pharmaceutical Co.for commercialization in Japan, Korea, and Taiwan

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Licensed to Merck Serono for development and commercialization outside of Japan, Korea, and Taiwan (October 2011)

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(7)

Merck KGaA Reaches Mutual Agreement with Ono Pharmaceutical to Terminate the License Agreement on Ceralifimod (ONO-4641)

Merck KGaA, 17 Jun 2014

Accessed on 23 Jun 2014 from http://news.emdgroup.com/N/0/CA6B3B25E9032894C1257CFA001FE133/$File/OnoEMD.pdf.

License agreement between Merck KGaA and Ono Pharmaceutical has been terminated because the drug does not meet Merck's conditions for continued investment (17 June 2014)

(7)

Merck KGaA Reaches Mutual Agreement with Ono Pharmaceutical to Terminate the License Agreement on Ceralifimod (ONO-4641)

Merck KGaA, 17 Jun 2014

Accessed on 23 Jun 2014 from http://news.emdgroup.com/N/0/CA6B3B25E9032894C1257CFA001FE133/$File/OnoEMD.pdf.

Names

Name:

ONO-4641

Trade name:

Ceralifimod

(7)

Merck KGaA Reaches Mutual Agreement with Ono Pharmaceutical to Terminate the License Agreement on Ceralifimod (ONO-4641)

Merck KGaA, 17 Jun 2014

Accessed on 23 Jun 2014 from http://news.emdgroup.com/N/0/CA6B3B25E9032894C1257CFA001FE133/$File/OnoEMD.pdf.

Synonyms:

MSC2430913A

(5)

A Safety and Efficacy Extension Study of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 14 Dec 2011

Accessed on 4 Jan 2012 from http://clinicaltrials.gov/ct2/show/NCT01226745.

ONO 4641

(8)

Substance Name: ONO 4641

US National Library of Medicine, National Institutes of Health

Accessed on 23 Jun 2014 from http://chem.sis.nlm.nih.gov/chemidplus/rn/1310090-01-7.

ONO4641

(8)

Substance Name: ONO 4641

US National Library of Medicine, National Institutes of Health

Accessed on 23 Jun 2014 from http://chem.sis.nlm.nih.gov/chemidplus/rn/1310090-01-7.

Physiology

Class:

Immunomodulator

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Target:

Sphingosine 1-phosphate receptor

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Properties:

In cynomolgus monkeys, reduces lymphocyte counts to their lowest levels 4 to 8 hours after administration

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Pharmacokinetic and pharmacodynamic responses in humans have been modeled using data from monkey studies and in vitro human metabolism data

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Mechanisms/Effects

Human:

Similar to other sphingosine 1-phosphate receptor modulators, thought to reduce circulating levels of lymphocytes

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Animal:

Reduces lymphocyte counts in cynomolgus monkeys

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Daily dose of a ONO-4641 prototype molecule improved symptoms in a mouse model of colitis

(3)

Therapeutic effects of novel sphingosine-1-phosphate receptor agonist W-061 in murine DSS colitis.

Sanada Y, Mizushima T, Kai Y, Nishimura J, Hagiya H, Kurata H, Mizuno H, Uejima E, Ito T

PLoS One. 2011; 6(9):e23933. Epub 2011 Sep 08. PMID: 21931623. Abstract

Treatment with ONO-4641 prototype molecule reduced Th1 and Th17 cell numbers but did not affect number of regulatory T cells in the lamina propria, a key pathogenic site in colitis

(3)

Therapeutic effects of novel sphingosine-1-phosphate receptor agonist W-061 in murine DSS colitis.

Sanada Y, Mizushima T, Kai Y, Nishimura J, Hagiya H, Kurata H, Mizuno H, Uejima E, Ito T

PLoS One. 2011; 6(9):e23933. Epub 2011 Sep 08. PMID: 21931623. Abstract

Regulatory and Commercial Status

Status for MS:

Phase II

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Highest status achieved (for any condition):

Phase II

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Other uses:

Preclinical study in colitis has been undertaken

(3)

Therapeutic effects of novel sphingosine-1-phosphate receptor agonist W-061 in murine DSS colitis.

Sanada Y, Mizushima T, Kai Y, Nishimura J, Hagiya H, Kurata H, Mizuno H, Uejima E, Ito T

PLoS One. 2011; 6(9):e23933. Epub 2011 Sep 08. PMID: 21931623. Abstract

Administration:

Oral

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(2)

The prediction of human response to ONO-4641, a sphingosine 1-phosphate receptor modulator, from preclinical data based on pharmacokinetic-pharmacodynamic modeling.

Ohno T, Hasegawa C, Nakade S, Kitagawa J, Honda N, Ogawa M

Biopharm Drug Dispos. 2010 Oct; 31(7):396-406. PMID: 20623701. Abstract

Negative effects:

Reduces heartbeat at the beginning of treatment

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Elevates liver enzymes

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Grade 4 lymphopenia

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Commercial:

Discovered by Ono Pharmaceutical Co.

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Developed by Ono Pharmaceutical Co.for commercialization in Japan, Korea, and Taiwan

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

Licensed to Merck Serono for development and commercialization outside of Japan, Korea, and Taiwan (October 2011)

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(7)

Merck KGaA Reaches Mutual Agreement with Ono Pharmaceutical to Terminate the License Agreement on Ceralifimod (ONO-4641)

Merck KGaA, 17 Jun 2014

Accessed on 23 Jun 2014 from http://news.emdgroup.com/N/0/CA6B3B25E9032894C1257CFA001FE133/$File/OnoEMD.pdf.

License agreement between Merck KGaA and Ono Pharmaceutical has been terminated because the drug does not meet Merck's conditions for continued investment (17 June 2014)

(7)

Merck KGaA Reaches Mutual Agreement with Ono Pharmaceutical to Terminate the License Agreement on Ceralifimod (ONO-4641)

Merck KGaA, 17 Jun 2014

Accessed on 23 Jun 2014 from http://news.emdgroup.com/N/0/CA6B3B25E9032894C1257CFA001FE133/$File/OnoEMD.pdf.

Key Clinical Trials

Placebo-controlled Trials:

Trial name:

Drug Research Evaluation for Multiple Sclerosis (DreaMS) trial (reported April 2012)

(1)

Ono to enter license agreements with Merck KGaA

ONO Pharmaceutical Co, 4 Oct 2011

Accessed on 3 Feb 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn111004.pdf.

(4)

A Study of the Safety and Efficacy of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 3 Feb 2012

Accessed on 20 Feb 2012 from http://clinicaltrials.gov/ct2/show/NCT01081782.

Phase:

Phase II trial

(4)

A Study of the Safety and Efficacy of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 3 Feb 2012

Accessed on 20 Feb 2012 from http://clinicaltrials.gov/ct2/show/NCT01081782.

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Study Design:

Company-sponsored, randomized, double-blind, placebo-controlled, multicenter, multinational study examining the effect of three doses of ONO-4641 on total the number of gadolinium-enhanced lesions, as measured every 4 weeks (primary endpoint)

(4)

A Study of the Safety and Efficacy of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 3 Feb 2012

Accessed on 20 Feb 2012 from http://clinicaltrials.gov/ct2/show/NCT01081782.

Disease Stage:

RRMS

(4)

A Study of the Safety and Efficacy of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 3 Feb 2012

Accessed on 20 Feb 2012 from http://clinicaltrials.gov/ct2/show/NCT01081782.

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Enrollment/Number of Patients:

407 patients

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Duration:

26 weeks

(4)

A Study of the Safety and Efficacy of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 3 Feb 2012

Accessed on 20 Feb 2012 from http://clinicaltrials.gov/ct2/show/NCT01081782.

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Status/Outcome:

Doses of 0.05, 0.10, or 0.15 mg reduced the number of gadolinium-enhanced lesions by 82%, 92%, and 77%, respectively, compared to placebo; adverse events appeared to be dose related

(6)

ONO-4641 Met Primary Endpoint of Phase II Study in Multiple Sclerosis Patients

17 April 2012

Accessed on 9 August 2012 from http://www.ono.co.jp/eng/news/pdf/sm_cn120417.pdf.

Head-to-Head Trials:

Other Trials:

Trial name:

A Safety and Efficacy Extension Study of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

(5)

A Safety and Efficacy Extension Study of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 14 Dec 2011

Accessed on 4 Jan 2012 from http://clinicaltrials.gov/ct2/show/NCT01226745.

Phase:

Phase II extension study

(5)

A Safety and Efficacy Extension Study of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 14 Dec 2011

Accessed on 4 Jan 2012 from http://clinicaltrials.gov/ct2/show/NCT01226745.

Study Design:

Extension study to examine the long-term safety and tolerability of ONO-4641(primary endpoint) in individuals who had finished the initial 26-week trial

(5)

A Safety and Efficacy Extension Study of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 14 Dec 2011

Accessed on 4 Jan 2012 from http://clinicaltrials.gov/ct2/show/NCT01226745.

Disease Stage:

RRMS

(5)

A Safety and Efficacy Extension Study of ONO-4641 in Patients With Relapsing-Remitting Multiple Sclerosis (DreaMS)

ClinicalTrials.gov, 14 Dec 2011

Accessed on 4 Jan 2012 from http://clinicaltrials.gov/ct2/show/NCT01226745.

Enrollment/Number of Patients:

376 (estimated enrollment)