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TV-3606 (Teva) is another phase I casualty. On the bright side (is it a bright side?) Teva is taking another stab at developing an oral formulation of copaxone, still in pre-clinical.

Last one on the phase I list, ZK811752 appears to have failed in 2005 in phase II trials. By the way, the report referenced below has some interesting info in case anyone wants to read up on drug development strategies.



BX-471 (ZK811752) is a recently developed oral chemokinereceptor (CCR1) antagonist. Positive results from phase I trials in autoimmune diseases including MS have been reported [216]. However, a double-blind, placebo controlled phase II study failed to demonstrate efficacy on primary or secondary outcome parameters [217].

http://www.sven-meuth.de/Files/pdf/P15.pdf

An abstract on a study of avonex and cellcept that shows promising results. The combination is in phase III right now.



Combination of IFNbeta-1a (Avonex(R)) and mycophenolate mofetil (Cellcept(R)) in multiple sclerosis.

Eur J Neurol. 2007 Jan;14(1):85-89.
* Vermersch P,
* Waucquier N,
* Michelin E,
* Bourteel H,
* Stojkovic T,
* Ferriby D,
* de Seze J;
* on behalf of the G-SEP (Groupe septentrional d'etudes et de prise en charge de la sclerose en plaques).
Department of Neurology, Hopital Roger Salengro, Lille, France.

To determine the safety of a combination of mycophenolate mofetil (Cellcept(R), MMF) and IFNbeta-1a (Avonex(R)) in relapsing-remitting multiple sclerosis (RRMS) and to evaluate the effects of the combination on clinical and magnetic resonance imaging (MRI) measures of disease activity. Secondary objectives were clinical and MRI data. An open-label, single-centre study including 30 RRMS patients was performed. Inclusion criteria were patients expanded disability status scale (EDSS) score <6.0, treated by Avonex(R) for at least 6 months, with at least two relapses during the previous 2 years and at least one during the previous 6 months. MMF at a progressive dose of 2 g per day orally was added to Avonex(R) for a duration of 6 months. MRI data were obtained at baseline and at the end of the study. The pre-study annual relapse rate was 2.0 +/- 0.7 and the EDSS score at baseline was 2.9 +/- 1.3. Eleven patients had gadolinium (Gd)-enhanced lesions at baseline for a total number of 35 lesions. Two patients interrupted the combination, one after the first dose for personal reasons unrelated to the study and the other due to diarrhoea. A few of the patients also reported nausea and abdominal pains. Adverse events included benign infectious diseases, insomnia and dizziness. No significant biological abnormalities were noted. The annualized relapse rate was 0.57 +/- 0.3 at the end of the study (P < 0.001). The mean EDSS score was 2.6 +/- 1.5 and no Gd-enhanced lesions were detected on MRI at the end of the study. MMF and IFNbeta-1a (Avonex(R)) combined therapy is safe and very well-tolerated. Clinical and MRI data suggest that this combination may be beneficial.

Pubmed reference

I can't find any references to the phase II trial of Fludarabine phosphate (aka Fludara) (with Avonex). Unfortunately, that means it's been deleted from the list. Let me know if anybody knows anything about anything...you know what I mean...

Based on this comment from a 2004 Schering report (!), I'm removing Mesopram from the phase II portion of the list:

"The development of Mesopram™ for the oral treatment of multiple sclerosis has been discontinued because other priorities required a shift in resources."

http://www.schering.de/html/en/50_media ... Item04.pdf

Based on recent posts from GWA and Bromley, I looked at the Neuren website. They have a substance (NNZ-2566) that just successfully completed a phase I trial. Their plans are to test it for other indications and there is no specific mention of when a trial for MS is planned, so I'm going to leave it in phase I until we hear some MS-related news. Here is their press release:

http://preset.sphilo.com/neuren/images/ ... 202007.pdf

OK, I'm finished going through the phase I and II lists to see if trials that have been going for a long time are still active. The last one I'm deleting is Xaliproden (aka SR 57746) (Sanofi-Aventis). I couldn't find anything about it being tested for MS. It is currently in phase III trials for alzheimers.

I must have a mental block in adding hormone trials to the list. This one isn't new, but isn't on the list yet.



http://clinicaltrials.gov/show/NCT00151801

Safety and Tolerability of Interferon-Beta-1a and Estroprogestins Association in MS Patients

This study is currently recruiting patients.
Verified by S. Andrea Hospital September 2005
Sponsored by: S. Andrea Hospital


Purpose
Clinical and experimental evidences suggests an immunomodulatory effect of sex hormones in multiple sclerosis.

The role of oral estroprogestins in the pathogenesis and in the clinical course of the disease is actually unknown.

The aim of the study is to investigate safety and tolerability of association of estroprogestins in two different doses with interferon-beta 1a in patients with relapsing-remitting multiple sclerosis.

Study Design
Treatment, Randomized, Single Blind, Dose Comparison, Parallel Assignment, Safety/Efficacy Study

Official Title
Safety and Tolerability of Oral Two-Doses Estroprogestins Associated With Interferon-Beta 1a in Patients With Relapsing-Remitting Multiple Sclerosis

Primary Outcomes
Safety assessment at 6, 12, 18 and 24 months, including adverse events, physical examination and laboratory parameters; Relapse rate at 6, 12, 18 and 24 months,; EDSS progression at 12 and 24 months,; MS functional composite score at 12 and 24 months,

Secondary Outcomes
Number and volume of new gad-enhancing lesions at 12 and 24 months; Number of new T1 and T2 lesions at 12 and 24 months; Brain volume changes at 12 and 24 months; Neuropsychological examination at 0, 12, 24 months; Hamilton scale for depression score at 0, 12, 24 months; MS Quality of Life scale score(MSQOL54)at 0, 12, 24 months; Fatigue Severity Scale score at 0, 12, 24 months

Expected Total Enrollment: 200
Study start: May 2002; Expected completion: April 2009
Last follow-up: December 2008; Data entry closure: February 2009
Phase 2, randomised, single blind, three arms study.
Follow-up of 24 months.
The study will include relapsing-remitting multiple sclerosis female patients.

Another new phase II study: "Fluoxetine in progressive multiple sclerosis: a placebo-controlled randomised trial".

The website with the link (below) is interesting. It is a meta-search site for clinical trials -- i.e. it searches a bunch of other clinical trial registries.

http://www.controlled-trials.com/mrct/t ... lerosis%22

dignan wrote:I must have a mental block in adding hormone trials to the list. This one isn't new, but isn't on the list yet.

MENTAL BLOCK?? I wish I had your kind of mental block! I'm lucky if I can keep the days straight....and there are only seven of those.
Bob

Another trial of minocycline with a CRAB. I'll just add a note to the existing minocycline phase II listing.


Minocycline as Add-on Therapy in Patients Being Treated With Rebif® for Relapsing-Remitting Multiple Sclerosis

This study is currently recruiting patients.
Verified by EMD Serono September 2006

http://clinicaltrials.gov/show/NCT00381459

with the new coke or old coke?

It looks like Acorda's Fampridine won't make it to market until late 2008, if it is approved.


Acorda Shares Fall After Downgrade
(AP) NEW YORK
Shares of biopharmaceutical company Acorda Therapeutics Inc. plunged Wednesday after an analyst downgraded the stock on the company's near-term outlook.

The stock fell $3.07, or 12.4 percent, to $21.75 on the Nasdaq Stock Market in morning trading. Shares have traded between $2.20 and $25.88 over the last 52 weeks.

The Hawthorne, N.Y.-based company on Tuesday reported a narrower fourth-quarter loss, as sales of Zanaflex muscle relaxant tablets and caplets surged to $8.2 million from $2.7 million.

Bank of America analyst William T. Ho on Tuesday downgraded the stock to "Neutral" from "Buy," but raised his price target to $26 from $21.

Ho said there will likely be few significant catalysts for the company until late in the year. He maintained a positive outlook for the developing multiple sclerosis drug Fampridine.

"We do expect the next trial to enroll faster than the previous trial and expect completion by late 2007 or the first quarter of 2008," he wrote in a note to investors.

The company expects to begin a second Phase III clinical trial on the drug candidate by the second quarter.Ho also cited higher-than-expected sales of Zanaflex as a positive, and said the company, with $53.8 million in cash, has sufficient funds to get it through the first quarter of 2008.

Lazard Capital Markets analyst Joel Sendek maintained a "Buy" rating and raised his price target to $28 from $24, citing strong sales of Zanaflex. He also expects the next Fampridine study to begin in the second quarter, but is looking at completion by the second quarter of 2008.

itsjustme wrote:It looks like Acorda's Fampridine won't make it to market until late 2008, if it is approved.

Luckily, we can get 4-AP compounded.

Another pre-clinical candidate, VX15, with Teva's backing.



Vaccinex inks deal with Teva

Rochester Business Journal -- February 27, 2007 -- Biotechnology firm Vaccinex Inc. has entered an alliance with Teva Pharmaceutical Industries Ltd. to develop and commercialize a human antibody discovered by Vaccinex.

Under the agreement, Israel-based Teva will make an equity investment in Vaccinex and pay undisclosed fees, development milestone payments and royalties on product sales to acquire an exclusive license for the development and commercialization of the antibody VX15 in multiple sclerosis and other disease indications. Antibodies are molecules produced by the body’s immune system to battle disease and infection.

Teva and existing Vaccinex investor, Pan Atlantic Bank and Trust Ltd., are lead investors in the local firm’s third major financing round, anticipated to exceed $25 million.

“This transaction demonstrates Vaccinex’s evolution from an antibody discovery company to a product-based company with a growing pipeline and increasing product development capabilities,” said Maurice Zauderer, Vaccinex’s president and CEO, in a statement.

The antibody VX15 represents a new targeted therapy that has the potential to improve efficacy in treating multiple sclerosis by both suppressing the body’s autoimmune response and blocking damage to the central nervous system, Vaccinex officials said. It also has shown the ability to destroy tumors in animal studies by inhibiting blood flow and starving cancer cells of nutrients and energy.

Vaccinex retains rights to oncology indications for VX15. It will continue to conduct all pre-clinical development activities, which will be funded by Teva, company officials said. Teva will have an option to join as a co-development partner in oncology after Vaccinex completes Phase I clinical trials. VX15 is one of four Vaccinex antibodies in pre-clinical development.

Zauderer called Teva a “tremendously valuable partner” for the antibody, due to its expertise in the multiple sclerosis market.

Vaccinex’s technology can generate functional antibodies against difficult targets. The firm employs 48 staffers at its Mount Hope Avenue site.

http://www.rbj.net/fullarticle.cfm?sdid=65049