Summary of the pipeline

A board to discuss future MS therapies in early stage (Phase I or II) trials.

Postby dignan » Mon Feb 23, 2009 8:13 pm

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.
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Postby mrhodes40 » Tue Feb 24, 2009 10:38 am

How interesting albuterol is a vasodilator among other things.........
interesting.
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Postby dignan » Thu Feb 26, 2009 10:35 pm

I took "IL-12/23 monoclonal antibody (Dartmouth-Hitchcock Medical Center)" off the phase 2 list because I just found out it is CNTO 1275, which I removed from the list a while back after it failed in a phase 2 trial.
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Postby dignan » Sat Feb 28, 2009 3:59 pm

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:

- Earnings conference call

- Investor presentation
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Postby mrhodes40 » Sat Feb 28, 2009 5:00 pm

Thanks Dignan! this is such a resource....... :D
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Re: PEGylated Inf-B

Postby NHE » Sun Mar 01, 2009 4:55 am

dignan wrote:I added "interferon beta 1a-PEGylated" to the phase 3 list. Biogen did a phase 1 already and is going straight to phase 3


Thanks for the update Dignan. Here's some information from their presentation...
Biogen wrote:PEGylated Interferon β 1a
  • PEGylated version of Interferon β-1a delivered via liquid prefilled syringe
  • Modified at the N-terminal α-amino group
  • Increased half-life and systemic exposure of the protein
  • May improve convenience and compliance for patients with MS who use Interferons
Clinical Data (Phase 1)
  • Phase 1 tested three doses over two months
  • Long-acting form has similar pharmacology to IFN β-1a
  • Doses identified were well-tolerated, no new safety signals
  • Presentation at 2009 AAN planned
Phase 3: Registration Study
  • Plan to initiate registration program in mid 2009
  • Placebo-controlled study in MS; 1260 patients
  • Primary endpoint: Annualized Relapse Rate at 1 year
  • To test biweekly and monthly SC dosing

In my opinion, one of the advantages of Avonex over the other Ifn-B's is that it's given via an intramuscular injection. As a result, there are no injection site reactions. This new formulation they're testing is via a subcutaneous injection. If it then has the same injection site reactions as Rebif and Betaseron, i.e., "injection site tissue necrosis", then I would have absolutely no interest in this new forumulation. Personally, I would rather go with more frequent dosing. Some time ago there was a thread on Twice a week Avonex. This would be more tolerable in my opinion.

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Postby dignan » Thu Mar 05, 2009 9:36 am

Based on the AAN abstract posted by Shayk, I added masitinib to phase 2.

http://www.abstracts2view.com/aan2009se ... 9L_P06.130
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Postby dignan » Sun Mar 08, 2009 7:38 pm

I removed "Interferon-tau (aka tauferon) (Pepgen)" from the phase 2 list because I found no evidence of an ongoing trial or that the company Pepgen is still in business.
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Postby dignan » Thu Mar 12, 2009 9:15 pm

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
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Postby dignan » Sat Mar 14, 2009 9:51 am

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.
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Postby dignan » Sat Mar 14, 2009 10:12 am

I removed N-acetyl-L-cysteine (with copaxone) from the phase 2 list because the trial is complete and I can't find any evidence of other ongoing trials.
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Postby dignan » Sat Mar 14, 2009 5:59 pm

Omega 3 is on the phase 2 list. I had seen a reference to a trial in Norway in a US MS Society .pdf document, but the link I had to that document is broken and I can't find it, or any other reference to that trial. However, I'm keeping it on the list for a bit as I did find an interesting article summarizing all of the trials of omegas for MS:

http://www.nature.com/ncpneuro/journal/v5/n2/full/ncpneuro1009.html#B18
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Postby dignan » Sun Mar 15, 2009 4:23 pm

I removed Pioglitazone (Actos) from the phase 2 list because it has been 2 years since the initial study results were 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.
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Postby dignan » Mon Mar 16, 2009 7:26 pm

I removed pirfenidone from the phase 2 list because I couldn't find any traces of planned or on-going MS trials, despite this promising SPMS study from a few years back.
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Postby dignan » Tue Mar 17, 2009 7:32 pm

I removed T-Cell Vaccination (Transnational University Limburg, Belgium/Netherlands) from the phase 2 list because I couldn't find any information about current or planned trials.
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