mspipeline

I removed “Atacicept (aka TACI-Ig) (Merck Serono and ZymoGenetics)” from the phase 2 list based on this article.

RTL1000 successfully completed a phase 1 trial, so I’m moving it to phase 2, based on this press release.

I moved PI-2301 from phase 1 to phase 2 based on this press release.

I moved Daclizumab from phase 2 to phase 3 based on this press release. The drug is still in a phase 2b trial for MS, but they are going ahead with planning for the phase 3 without waiting for the conclusion of the phase 2. I don’t know if this is because Facet Biotech is really confident in daclizumab, or if they are trying to impress investors or get some kind of milestone payment from Biogen.

I removed MBP8298 (aka Dirucotide) (BioMS) (trials for SPMS and RRMS) from both the phase 2 and phase 3 lists based on this press release.

I know a significant number of phase 3 candidates fail, but it’s still disappointing when one does, especially one that was being tested on progressive MS.

I removed CDP323 (UCB / Biogen) from the phase 2 list based on this news.

I added LY2127399 (Anti-BAFF Human Antibody) (Eli Lilly) to the phase 2 list based on this webpage.

Based on this information from a trial participant, I have removed “Lamotrigine (aka Lamictal) (SPMS) (Glaxosmithkline)” from the phase 2  list.

I added BAF312 (Novartis) to the phase 2 list based on this.

I moved Helminth-Induced Immunomoducation Therapy from phase 1 to phase 2 based on this clinicaltrials.gov page. An abstract of the phase 1 results is available here.

I’m adding Prolactin (Stem Cell Therapeutics / U of Calgary) to the phase 1 list based on a bunch of stuff. Thanks to Marcy for the tip.

From the Stem Cell Network:
Endogenous progenitor cell repair in multiple sclerosis (Core) Investigators:  Samuel Weiss (project leader), University of Calgary; Voon Wee Yong, University of Calgary; Jack Antel, McGill University; Luanne Metz, University of Calgary.

Project summary: Building on previously funded SCN research, this project includes basic research and a clinical trial to identify and test the role of prolactin, a pituitary hormone, in the repair of damaged myelin in patients with Multiple Sclerosis (MS).

Partners: Swartout Centre for MS Neuroprotection and Repair – Hotchkiss Brain Institute; Neuroscience Canada Foundation; Stem Cell Therapeutics Corp.

Benefits: The overall goal is to develop a novel therapeutic approach to treat MS patients.
http://www.stemcellnetwork.ca/projects.php

From Stem Cell Therapeutics (SCT):
SCT has substantial intellectual property relating to the use of neurogenic agents for treating demyelinating diseases such as multiple sclerosis (MS). Previous scientific investigations have characterized two potentially important therapeutic effects of prolactin on the CNS. In these published studies prolactin has been shown to act as both a neurogenic agent to increase the number of progenitor cells that mature into oligodendrocytes and as an agent that promotes remyelination of the brain in the presence of disease conditions. SCT was recently granted two key patents for the use of prolactin in neurologic diseases authored by Dr. Samuel Weiss from the University of Calgary and based on demonstrated insights into the effect of prolactin. Moreover, recent publications (Journal of Neuroscience, Feb. 21, 2007 ‘White Matter Plasticity and Enhanced Remyelination in Maternal CNS’ by Drs Yong and Weiss) strongly support and validate the concept that prolactin may represent a potential new therapeutic platform for the treatment of white matter injury, and an mpetus for a clinical program aimed at treating patients with multiple sclerosis. Successful completion of a preliminary non-clinical study undertaken by Dr Wee Yong at University of Calgary is expected to quickly evolve into a clinical program to demonstrate efficacy in patients diagnosed with multiple sclerosis. The results of this study are anticipated to be announced in early 2009, and the follow-on clinical study that will be lead by Dr Luann Metz at the University of Calgary is anticipated to begin in Q3 2009. This study is expected to be funded by an outside grant to the University of Calgary.
http://www.stemcellthera.com/pdf/SCT3Q08MD_A.pdf

A couple of other miscellaneous links:
- http://cnrp.marketwire.com/cnrp_files/20080707-707sss.pdf
- http://cnrp.marketwire.com/cnrp_files/20090409-409SSS1.pdf

I added two studies to the phase 1 list: Low Fat Diet and Linoleic Acid.

Based on this press release, I added Valomaciclovir (EPB-348) to the phase 1 list.

I removed T-Cell Vaccination (Transnational University Limburg, Belgium /Netherlands) from the phase 2 list because I couldn’t find any indication that there is a trial either planned or on-going.

I removed Pirfenidone (aka Deskar) from the phase 2 list because I can find no evidence that there are any further MS trials planned or on-going, despite somewhat promising results in a phase 2 SPMS trial a few years ago.

I removed Pioglitazone (Actos) from the phase 2 list because it has been 2 years since the initial study was reported and I haven’t found any information about a new trial planned or in progress. Takeda, the company that produces Actos, does not mention anything about an MS trial in their pipeline.

I removed N-acetyl-L-cysteine (with copaxone) from the phase 2 list because the trial is complete and I can find no evidence of other on-going trials.

I removed Inosine (Thomas Jefferson University) from the phase 2 list because the trial is complete and I can’t find any evidence of additional inosine trials in progress.

I removed MLN1202 (Millenium) from the phase 2 list because I found no evidence that it was anything more than a figment of my imagination.

http://www.millennium.com/science/pipeline.asp

I moved lipoic acid from phase 2 to phase 1 because I couldn’t find any evidence that the phase 2 trial (for SPMS) with interferon is actually happening. The phase 1 trial should be over or ending soon and is for RRMS.

I removed “Interferon-tau (aka tauferon) (Pepgen)” from the phase 2 list because I can find no evidence that a trial is ongoing or that the company Pepgen still exists.

I added Masitinib to phase 2 based on this abstract from the upcoming AAN meeting, and this document (page 47).

I added “interferon beta 1a-PEGylated” to the phase 3 list. Biogen did a phase 1 already and is going straight to phase 3, I assume because interferon has already been studied to death, and there are even pegylated versions of other interferons on the market (not for MS). The final bonus is that the phase 3 trial will only be for 1 year, not the usual 2 years (again, I assume because of the level of study that has already gone into similar substances). The trial is expected to start mid-year.

Sources:
- http://seekingalpha.com/article/119054-biogen-idec-q4-2008-earnings-call-transcript?page=4

- http://library.corporate-ir.net/library/14/148/148682/items/323432/703556BC-623A-424B-81E5-8236B14E0A21_BIIBQ408Slides.pdf

I removed “IL-12/23 monoclonal antibody (Dartmouth-Hitchcock Medical Center)” from the phase 2 list because I just discovered that it’s the same thing as CNTO 1275, which I took off the list a while back because it failed in a phase 2 trial.

These results were presented at the ECTRIMS, ACTRIMS and LACTRIMS conference in September. This trial was listed in phase 2 as “Albuterol (aka Proventil) (with Copaxone)”. The trial is done, so I’m removing it from the list.

Treatment of multiple sclerosis with glatiramer acetate and albuterol: results of a clinical trial

P. Kivisäkk1; V. Viglietta2; B. Healy1; G. J. Buckle1; H. L. Weiner1; D. A. Hafler1; S. Khoury1
1. Brigham and Women’s Hospital, Boston, MA, USA., 2. EMD Serono, Boston, MA, USA.

The mechanism of action of glatiramer acetate (GA) is thought to be by induction of anergy of GA reactive lines and enhanced production of Th2 cytokines. We hypothesized that albuterol may enhance the effects of GA in vivo or accelerate the induction of anergy and Th2 cytokine production.

In a randomized, double-masked, two-arm pilot study we investigated the effect of adding oral albuterol versus placebo to GA in relapsing–remitting multiple sclerosis (RRMS).

Eligibility criteria were clinically definite RRMS with positive brain magnetic resonance imaging (MRI), and an Expanded Disability Status Scale (EDSS) score between 0 and 3.5. No prior treatment with GA or oral myelin. No treatment with immunomodulating therapy within the past 3 months. No prior treatment with immunosuppressants. No steroid treatment 1 month prior to study entry. Subjects were randomized to two treatment arms: 20mg SQ of GA daily + 4mg PO of placebo daily for 2 years or 20mg SQ of GA daily + 4mg PO of albuterol daily, for 2 years.

The primary outcome measures were the change in the MS Functional Scale (MSFC), and the change in IL-13 and IFN-γ cytokine secretion by GA reactive T cell lines. Secondary outcome variables included changes in percentage of IL-12-producing monocytes by intra-cytoplasmic staining, time of first exacerbation, number and severity of exacerbations, and MRI evidence of progression.

Forty four subjects were randomized (21 in the GA+placebo arm and 23 in the GA+albuterol arm). There was a treatment effect of albuterol on MSFC at 6 months that diminished over time (p=0.026) and a trend for improved MSFC in the albuterol arm at 12 months. Analysis of the immunologic endpoints is ongoing.

Albuterol added to GA treatment in RRMS enhanced treatment response in the early time points and may be beneficial in accelerating the beneficial effects of therapy.

I added a schwack (five) of new stem cell trials from clinicaltrials.gov. They are all in phase 1 and 2.

http://www.clinicaltrials.gov/ct2/show/NCT00813969

http://www.clinicaltrials.gov/ct2/show/NCT00288626

http://www.clinicaltrials.gov/ct2/show/NCT00273364

http://www.clinicaltrials.gov/ct2/show/NCT00781872

http://www.clinicaltrials.gov/ct2/show/NCT00497952

I added ESP, from Biomolecular Pharma and Mount Allison University, to the phase 2 list based on this press release and this paper.

I added ONO-4641 to the list in phase 1 based on this (page 17).

From this paper, I realized that 2 of the substances in phase 1 are the same thing. FYAK is PI-2301.

I added “Far Infrared Irradiation” to phase 1 based on this information.

Just added:

- Flupirtine (Bayer Schering) to phase 2 based on this.

- CS-0777 (Daiichi-Sankyo) to phase 1 based on this.

I added a phase 3 PPMS trial for FTY720 based on this info.

Added hookworms to the phase 2 list based on this information from the UK MS Society.

I removed 40mg copaxone from phase 3 based on these results.

Added “BaroFeron” from BaroFold to phase 1. It is a new formulation of beta interferon, so not exactly exciting news…

I added LymphoStat-B (belimumab) from Human Genome Sciences and Glaxosmithkline to phase 2, based on this press release.

I added a link to a phase 2 zocor (simvastatin) trial for SPMS recruiting now in the UK.

http://www.mssociety.org.uk/research/take_part_in_research/simvastatin.html

I moved MN-166 from phase 2 to phase 3 based on their release of successful phase 2 trial results. They don’t have the regulatory go-ahead for phase 3, but I’ll assume they will get it.

Based on this article, I added FYAK to phase 1.

I removed Osteopontin (aka TACI-Ig) (Merck Serono and ZymoGenetics) from phase 1 as it is no longer listed in Merck Serono’s pipeline.

I removed AVE9897 (Sanofi-Aventis) from phase 1 as the drug is no longer listed in the company’s pipeline.

I moved helminth induced immunomodulation from pre-clinical to phase 1 based on this article.

I added BGC20-0134 from BTG to the phase 1 list based on this article.

I’m adding TBC-4746 from Encysive Pharmaceuticals to the phase 1 list. The company is in the process of being bought out by Pfizer. The drug is a VLA-4 antagonist, like tysabri, but is taken orally.

http://www.encysive.com/clinical.html

http://www.encysive.com/products.html

I removed “Topiramate (aka Topamax) (with Avonex)” from the phase 2 list as I can’t find any information that shows it is still going.

I added GRC 4039, from Glenmark Pharmaceuticals, to the pipeline in phase 1.

Related to the last update, Genentech announced that they are not going ahead with rituxan for RRMS (they are continuing with the PPMS trial). The reason is that ocrelizumab goes after the same target and they are concentrating on that drug for RRMS. I removed Rituxan from the phase 2 list.

Added Ocrelizumab (R1594) (Roche/Genentech/Biogen) to phase 2.

The CUPID study of cannabinoids (currently on the list in phase 2) in the UK is:

- double-blind
- placebo-controlled
- multi-centre
- 3 years in duration
- and is aiming for enrollment of 500 people

I keep looking for some mention of what phase trial this is but can’t find any. So, if it looks like a duck, walks like a duck and quacks like a duck, I’m going to call it a duck…in this case, a phase 3 trial.

I removed A4I from the phase 2 list due to this page at clinicaltrials.gov.

I removed SGN-30 from the phase 1 list as Seattle Genetics no longer mentions multiple sclerosis anywhere on their website.

I deleted Neuren’s NNZ-2566 from phase 1 as the Neuren website makes no mention of MS trials, and they say:

Neuren’s strategy is to undertake clinical trials for acute conditions, which are generally shorter and less expensive than those for chronic conditions. This strategy provides the most cost-effective means of increasing shareholder value while controlling risk.

Neuren decides which targets to pursue and which compounds to develop only after consideration of the cost and complexity of trials, the ease with which results can be validated, and assessment of market need and commercial opportunity.

I removed Medarex’s MDX1100 from phase 1 because they are going forward with an ulcerative colitis trial, but the company’s website contains no mention of MDX1100 for MS that I could see.

Today is all about Merck Serono. Two substances that were in Serono’s pipeline in phase 1, “JNK inhibitor” and “MMP-12 inhibitor” are no longer there. I’ve removed them from the list. The Serono compound “Osteopontin” has moved from pre-clinical to phase 1. The best news is that Merck Serono has added a substance, Atacicept, to their pipeline in phase 2. It is a collaboration with ZymoGenetics. The drug was formerly known as TACI-Ig. It is also being tested for lupus and RA.

Added R3477 (Roche / Actelion) to phase 1 based on this and this.

Added Amiloride to phase 1 based on this BBC article.

I moved ATX-MS1467 (Apitope Technology) from phase 1 to phase 2 based on a company press release

I moved the helminth trial from phase 2 to pre-clinical based on information from Bob, who was in contact with the trial sponsor.

Bayer announced that their trial of a 500 mcg dose of betaseron failed to meet its primary end point. I removed it from the phase 3 list.

I added ATX-MS1467 from Apitope Technology to the phase 1 list based on this.

I moved HP184 (Sanofi-Aventis), from pre-clinical to phase 2. It is now called nerispirdine. Based on this, HP184 is a K+ / Na+ channel blocker. Channel blockers have shown some promise in offering neuroprotection, so let’s hope this one is successful.

I added a trial of Sunphenon EGCg (Epigallocatechin-Gallate) to the phase 2 list based on this.

I moved Peptimmune’s PI-2301 from pre-clinical to phase 1 based on this.

Based on this information from the MS Society of Canada, I added minocycline to phase 3. Woohoo! I’m keeping it in phase 2 as well because there are two phase 2 trials with minocycline ongoing.

Based on this report that the new Rebif formulation has been approved by the EU regulatory authority, I ‘m taking the trial out of phase 3 and updating the approved list to reflect that rebif is the “new version”.