Summary of the pipeline

dignan · Post by **dignan** » Sat May 02, 2009 4:36 pm

Here are those latest tovaxin results I was thinking of, from the AAN meeting:

TERMS Trial T-Cell Vaccination Secondary Analysis of Clinical and Immunologic Outcomes in Relapsing Remitting Multiple Sclerosis Patients

Edward J. Fox, Round Rock, TX, Clyde E. Markowitz, Philadelphia, PA, Stanley Cohan, Lake Oswego, OR, Daniel R. Wynn, Northbrook, IL, Donna Rill, Mary Riser, Jim Williams, The Woodlands, TX

OBJECTIVE: To assess clinical and immunologic outcomes of the TERMS (Tovaxin for Early Relapsing Multiple Sclerosis) trial multiple sclerosis patients through secondary analyses in a prospectively identified group of patients.

BACKGROUND: The TERMS study was a Phase IIb multi-center, randomized, double blind, placebo-controlled trial in 150 patients with Relapsing-Remitting Multiple Sclerosis or high risk Clinically Isolated Syndrome to assess the safety and efficacy of T-cell vaccination.

DESIGN/METHODS: 100 patients received Tovaxin and 50 received placebo. Patients were given five subcutaneous injections at weeks 0, 4, 8, 12, and 24 with safety and efficacy assessments occurring through week 52. A secondary analysis of clinical and immunologic parameters was conducted on a group of patients (n=50; 32 Tovaxin and 18 placebo) with a pre-study ARR of greater than 1. Information was gathered on both clinical and immunologic parameters.

RESULTS: Statistical significance of reduced disability by the Expanded Disability Status Scale (EDSS) (p=0.045) was found for patients treated with Tovaxin (28.1% Tovaxin vs. 5.6% placebo) and demonstrated an ARR of 0.28 (55 percent reduction compared to 0.63 on placebo). The Timed 25 foot Walk showed a benefit for Tovaxin over placebo (0.14 vs. -0.02). Brain atrophy was reduced by 88 percent with a 20 percent reduction in the number of gadolinium (Gd) lesions progressing to black holes. Patients with less myelin T-cell reactivity had a lower risk of relapse.

CONCLUSIONS/RELEVANCE: Tovaxin treatment demonstrated a benefit across clinical and magnetic resonance imaging (MRI) endpoints. The immunology and epitope database assessment suggests that those patients exhibiting a greater T-cell reactivity often demonstrated a worsening of at least one MRI endpoint (Gd lesion, Gd volume, new T2 count or progression to black holes) and one clinical endpoint (either relapse or EDSS). The converse also appears true, where T-cell reactivity resulted in an absence of worsening of MRI and clinical endpoints.

http://www.abstracts2view.com/aan2009se ... 9L_P06.132

Lars · Post by **Lars** » Sun May 03, 2009 8:55 am

Thanks Dignan,
One has to wonder where the hell this report was when they pulled our plug.
Lars

notasperfectasyou · Post by **notasperfectasyou** » Tue May 19, 2009 11:26 am

bromley wrote:Aspirin is also in trial

This is suddenly more interesting. Was this study completed? Ken

dignan · Post by **dignan** » Tue May 19, 2009 11:59 am

Yes, the trial was completed in 2004. Here is what I found (couldn't find a free version of the full results...anyone?...anyone?...Bob?...).

A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis.

Neurology. 2005 Apr 12;64(7):1267-9.
Wingerchuk DM, Benarroch EE, O'Brien PC, Keegan BM, Lucchinetti CF, Noseworthy JH, Weinshenker BG, Rodriguez M.
Department of Neurology Mayo Clinic, Scottsdale, AZ 85259, USA. wingerchuk.dean@mayo.edu

Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue.

http://www.ncbi.nlm.nih.gov/pubmed/15824361

Also, here, there is a bit of an assessment of the aspirin trial:

http://ms.about.com/od/newsresearch/a/a ... atigue.htm

notasperfectasyou · Post by **notasperfectasyou** » Tue May 19, 2009 12:22 pm

Interesting! They used 1300 mg, which comes from a study done in 1979 on Lymphocyte Adhearance. Funny how you get the feeling these research folks use one idea to sell the study so they can backdoor into a different idea, isn't it? Ken

Lyon · Post by **Lyon** » Tue May 19, 2009 12:57 pm

dignan · Post by **dignan** » Tue May 19, 2009 1:31 pm

Bob, you are a scholar and a gentleman.

dignan · Post by **dignan** » Tue May 19, 2009 1:54 pm

Thanks to the MS Society clinical trials document posted today by Bromley, I added BAF312 (Novartis) to the phase 2 list, based on this:

http://www.clinicaltrials.gov/ct2/show/NCT00879658

dignan · Post by **dignan** » Sat May 23, 2009 8:40 am

I removed "Lamotrigine (aka Lamictal) (SPMS) (Glaxosmithkline)" from the phase 2 list based on this post from Muu: http://www.thisisms.com/ftopict-7295.html

dignan · Post by **dignan** » Tue May 26, 2009 7:21 pm

Maybe I removed pioglitazone from the list too soon (back in March)...but I don't think I'll add it back until they announce that they have the funding for another trial...

Diabetes drug shows promise against multiple sclerosis

May 26th, 2009 -- A drug currently FDA-approved for use in diabetes shows some protective effects in the brains of patients with relapsing remitting multiple sclerosis, researchers at the University of Illinois at Chicago College of Medicine report in a study currently available online in the Journal of Neuroimmunology.

In a small, double-blinded clinical trial, patients with relapsing remitting multiple sclerosis were assigned to take pioglitazone (a drug commercially known as Actos used to treat type-2 diabetes) or a placebo. Patients continued their normal course of therapy during the trial.

Standard neurological tests were done initially, as were MRI scans to provide baseline values for lesions typically seen in MS patients. The patients were evaluated every two months, and blood samples were taken. Repeat MRI scans were done after five months and again after one year.

Patients taking pioglitazone showed significantly less loss of gray matter over the course of the one-year trial than patients taking placebo. Of the 21 patients who finished the study, patients taking pioglitazone had no adverse reactions and, further, found taking pioglitazone, which is administered in an oral tablet, easy.

"This is very encouraging," said Douglas Feinstein, research professor of anesthesiology at UIC. "Gray matter in the brain is the part that is rich in neurons. These preliminary results suggest that the drug has important effects on neuronal survival."

Feinstein's lab has been interested in the class of drugs called thiazolidinediones, or TZDs. Several TZDs have been approved for use in the treatment of type-2 diabetes because of the drugs' effect on the body's response to insulin.

The researchers focused on pioglitazone because of its known anti-inflammatory effects, Feinstein said. They used primary cultures of brain cells to show that pioglitazone reduced the production of toxic chemicals called cytokines and reactive oxygen species. These molecules are believed to be important in the development of symptoms in MS.

Feinstein's lab proceeded to test pioglitazone in an animal model of MS. They and others showed that pioglitazone and other TZDs "can significantly reduce the clinical signs in mice with an MS-type disease," said Feinstein.

"More importantly, when mice who are already ill are treated with pioglitazone, the clinical signs of the disease go away," he said. "We were able to induce almost complete remissions in a number of mice."

"We are now working to determine the mechanisms to explain the protective effect on neurons that we see in our studies," said Feinstein. "We hope to expand into a larger trial to confirm these preliminary results."

http://www.physorg.com/news162578834.html

dignan · Post by **dignan** » Tue Jun 02, 2009 4:13 pm

I added "LY2127399 (Anti-BAFF Human Antibody) (Eli Lilly)" to the phase 2 list based on a clinicaltrials.gov listing:

http://www.clinicaltrials.gov/ct2/show/NCT00882999

RuSmolikova · Post by **RuSmolikova** » Tue Jul 07, 2009 11:18 am

CDP 323 has failed:
http://www.medicalnewstoday.com/articles/156171.php

dignan · Post by **dignan** » Tue Jul 07, 2009 12:49 pm

Wow! Thanks for the the update. I'm surprised by this one since it goes after the same target as tysabri. I was guessing that it would be effective, but could have PML problems.

RuSmolikova · Post by **RuSmolikova** » Tue Jul 07, 2009 1:15 pm

No cases of PML were noted...

dignan · Post by **dignan** » Mon Jul 27, 2009 8:23 pm

I removed MBP8298 (aka Dirucotide) (BioMS) (trial for SPMS and RRMS) from the phase 2 and phase 3 lists based on this link from Cheer:

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