From Nat'l MS Society- New drug going before FDA

[Audrey_M]

First oral disease modifier goes to FDA review panel

After accepting Gilenia (fingolimod) for priority review, the FDA advisory panel meets on June 10 to make a

recommendation. Witnesses may include Dr. Patricia O’Looney of the Society’s Research & Clinical Programs —

and people with MS who may testify to their need for more treatment options. If recommended for approval,

Novartis may market Gilenia — the very first MS disease modifier in pill form — within the next six months.


http://www.nationalmssociety.org/news/news-detail/index.aspx?nid=2568

Jan 20, 2010

Positive Results Published on Clinical Trials of Oral FTY720 (Fingolimod) for Relapsing MS -- Novartis Applies to FDA and European Regulatory Agency for Approval

Positive results from two large-scale phase III clinical trials of oral fingolimod (FTY720) have been published

showing it significantly reduced multiple sclerosis relapse rates, and one of the trials also suggested it could slow

the progression of disability. The sponsor, Novartis International AG, has announced that it applied for marketing

approval in the U.S. and European Union in December 2009. There are currently no approved oral disease-

modifying therapies for MS. The papers were published early online in the New England Journal of Medicine (links

one and two) on January 20, 2010, along with a separate paper that describes results from a clinical trial of another

orally administered experimental therapy, cladribine.


About Fingolimod: This is a new class of therapy in development for treating multiple sclerosis. FTY720 binds to a

docking site (sphingosine-1-phosphate receptor, or S1P receptor) on immune cells, including T cells and B cells,

that have been implicated in causing nervous system damage in MS. The drug appears to induce immune cells to

remain in lymph nodes, where they can do little harm, preventing them from migrating into the brain and spinal cord.


First in-depth study results published: One paper, by Ludwig Kappos, MD (University Hospital, Basel, Switzerland)

and colleagues, describes results from the large-scale, two-year phase III trial known as FREEDOMS, involving

1,272 people with relapsing-remitting MS. Over two years, fingolimod at either of two doses was able to

significantly reduce relapse rates (the primary endpoint of the study) and slow disability progression (a secondary

endpoint) compared to those on inactive placebo. Relapse rates were 0.18 for the lower dose, 0.16 with the higher

dose, and 0.40 for those on placebo (a reduction of 54% and 60% over placebo, respectively). Disease progression

was measured by standard MS clinical rating scales known as the EDSS and MSFC, and after 24 months both

doses showed slower progression over those on placebo. Secondary measures of disease activity and progression

also favored both FTY720 doses, including MR imaging to detect tissue injury and brain atrophy.


The second paper, by Jeffrey A. Cohen, MD (Cleveland Clinic, Cleveland, Ohio) and colleagues, details positive

results from a one-year clinical trial, called the TRANSFORMS study, comparing two different doses of fingolimod

with Avonex® (interferon beta-1a, Biogen Idec). That study involved 1,292 individuals with relapsing-remitting MS.

Both doses of FTY720 were able to reduce relapse rates over one year (the primary endpoint of the study), and

also reduced disease activity on MR brain imaging. The annualized relapse rate in those taking the lower dose of

FTY720 was 0.16, compared to 0.33 in those on Avonex (a comparative reduction of 52%). Those taking the higher

dose of FTY720 experienced an annualized relapse rate of 0.20 (a reduction of 38% compared with Avonex). Time

to sustained disability progression was no different in the FTY720 and Avonex groups.


Safety: In both studies, the lower dose of FTY720 was better tolerated. A few participants experienced a transient

reduction in heart rate and blockage of heart conduction (atrioventricular conduction block) which generally

normalized after the first dose. There was a slight elevation of blood pressure starting during the second month of

therapy. Macular edema (swelling of the center of the retina inside the eye) occurred more frequently with those on

the higher dose of FTY720 in both studies. Skin cancers were reported more frequently in those on FTY720 in the

one-year TRANSFORMS study, but more malignancies in general were detected in those on placebo in the two-

year FREEDOMS study.


Elevations in liver enzymes, without accompanying symptoms, were common in those receiving FTY720. In both

studies, a small number of serious herpes infections occurred, including two deaths from herpes infections that

occurred in the TRANSFORMS trial in people taking the higher dose of FTY720.


Next Steps: According to the company, these and other data were used to support applications for marketing

approval for the lower dose of FTY720, which were submitted in December 2009 to the U.S. Food and Drug

Administration and to the European Medicines Agency.


Results from a second large-scale trial called FREEDOMS II have not yet been released. Other phase 3 clinical

trials of fingolimod, including one involving people with primary progressive MS, are still under way, as are

extension studies involving those who’ve completed trials. These should provide additional data on safety and

efficacy.


Comment: “The published results and the company’s application for marketing approval for fingolimod are wonderful

news for people with MS,” said John R. Richert, MD, Executive Vice President of Research and Clinical Programs

at the National MS Society. “Having oral therapies in the MS pipeline is real progress, and it should increase the

number of people who choose to begin therapy earlier and who stay on therapy, which our experts say is the best

way to combat future disease activity.”

(Avonex is a registered trademark of Biogen Idec)

[HVAC]

I heard a MS Researcher speak of these drugs three weeks ago. These new class of MS Drugs will be a lot better at stopping relapses.

There is one problem they will cause more and worse side effects than the CRABs .He is doing a study of fingolimod for PPMS. at Duke.

He says they will be very expensive as well when they do come to market.

For this reason many Neurologists and insurance Companies will want to stick with CRABs unless you do not respond to them at all.

Alex

[Audrey_M]

Sorry about the formatting. I tried to double space this to make it easier for others to read, but it fragmented sentences. I can repost the article single spaced, but it is long.

I did use the "contact us" to suggest that they improve the functionality of forums with spell check and formatting. I had pasted this into word and double spaced it, but this web site took all of my hard work away!