Multiple Sclerosis (MS) Support Group

Another link to Cladribine announcements..

http://www.itnews.it/news/2009/0123080201940/merck-serono-s-oral-investigational-treatment-cladribine-tablets-for-multiple-sclerosis-significantly-reduced-relapse-rate-in-two-year-phase-iii-pivotal-trial.html

*****

GENEVA, Switzerland, January 23 /PRNewswire/ --
- Two-Year Primary Efficacy Endpoint of CLARITY Trial met: 58% Relative Reduction in Annualized Relapse Rate in the low Total Dose Treatment Group and 55% in the High Total Dose Treatment Group
- Submission for Registration of Cladribine Tablets Planned for mid-2009
- Cladribine Tablets are the First Oral Investigational Multiple Sclerosis Treatment to Complete a Two-Year Pivotal Study
Merck Serono, a division of Merck KGaA, Darmstadt, Germany, announced today that the CLARITY(1) Phase III pivotal trial of its proprietary oral formulation of cladribine (cladribine tablets) met the two-year primary endpoint of clinical relapse rate reduction in patients with relapsing-remitting multiple sclerosis (MS).
The two cladribine tablet treatment groups of the study, assessing different dose regimens, demonstrated a statistically significant reduction in the annualized rate of relapses compared to placebo. Patients from the lower total dose group experienced a 58% relative reduction in annualized relapse rates with respect to placebo (0.14 versus 0.33 for the placebo group; pOverall, the frequencies of adverse events were low in the cladribine tablet treatment groups and were comparable to that observed in the placebo group. Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the cladribine tablet treatment groups. With the exception of lymphopenia, the most frequently reported adverse events in the three study groups were headaches and nasopharyngitis.
"We believe the CLARITY data mark an important milestone in the assessment of investigational oral treatments for multiple sclerosis and that cladribine tablets have the potential to make a real difference in the lives of patients," said Elmar Schnee, President of Merck Serono. "Based on the successful completion of the CLARITY study, we plan to submit cladribine tablets for registration to the EMEA and to the FDA for mid-2009."
Secondary endpoints of the CLARITY study were also met, including reduction of lesion activity as measured by magnetic resonance imaging (MRI), proportion of subjects relapse-free and disability progression. Full study results will be submitted for presentation at an upcoming scientific meeting.
The CLARITY study was a two-year (96 weeks), randomized, double-blind, placebo-controlled, international trial. It enrolled 1,326 patients with relapsing-remitting MS according to the revised McDonald criteria(2). Study participants were randomized to one of three different treatment groups consisting of two different dose regimens of cladribine tablets or matching placebo tablets (1:1:1 ratio). Cladribine tablets were given in two or four treatment courses in the first year, with each course consisting of once daily administration for four to five consecutive days, which means study patients took cladribine tablets for only 8 to 20 days during the year. In the second year, two treatment courses were administered to all patient groups. The primary endpoint of the CLARITY study was the qualifying relapse rate at 96 weeks. Secondary endpoints included MRI endpoints(3), proportion of subjects relapse-free and disability progression at 96 weeks. Out of the 1,326 randomized patients, 90% of patients treated with cladribine tablets completed the study (92% in the lower total dose group and 89% in the higher total dose group) compared to 87% in the placebo group.
About cladribine tablets
Merck Serono's proprietary oral formulation of cladribine (cladribine tablets) is currently being evaluated in Phase III as a treatment for patients with relapsing forms of multiple sclerosis (MS). Cladribine is a small molecule that may interfere with the behavior and the proliferation of certain white blood cells, particularly lymphocytes, which are thought to be involved in the pathological process of MS.
The clinical development program for cladribine tablets includes:
- The CLARITY (CLAdRIbine Tablets Treating MS OrallY) extension study: a two-year placebo-controlled extension of the CLARITY study, designed to provide data on the long-term safety and efficacy of extended administration of cladribine tablets for up to four years
- The ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS). This trial was announced in September 2008.
- The ONWARD (Oral Cladribine Added ON To Rebif New Formulation in Patients With Active Relapsing Disease) study: a Phase II placebo-controlled trial designed primarily to evaluate the safety and tolerability of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy. This trial was announced in January 2007.
Cladribine tablets have been granted a fast track designation by the US Food and Drug Administration based on the need for an oral therapy in a subset of patients with relapsing forms of multiple sclerosis.
About Merck Serono and multiple sclerosis
Merck Serono is a leader in multiple sclerosis (MS) with Rebif(R) (interferon beta-1a), a disease-modifying drug used to treat relapsing forms of MS, which is registered in more than 80 countries worldwide. Full prescribing information for this product can be obtained by contacting the Company or visiting its website. Additional therapeutic options are currently under development at Merck Serono, including cladribine tablets, currently in Phase III and potentially the first oral therapy for MS, as well as several products in early stage development. Merck Serono also is taking a leading role in developing an understanding of the role of genetics in MS.
About multiple sclerosis
Multiple sclerosis (MS) is a chronic, inflammatory condition of the nervous system and is the most common, non-traumatic, disabling neurological disease in young adults. The World Health Organization estimates that up to 2.5 million people suffer from MS worldwide. While symptoms can vary, the most common symptoms of MS include blurred vision, numbness or tingling in the limbs and problems with strength and coordination. The relapsing forms of MS are the most common.
About Merck Serono
Merck Serono is the division for innovative prescription pharmaceuticals of Merck, a global pharmaceutical and chemical group. Headquartered in Geneva, Switzerland, Merck Serono discovers, develops, manufactures and markets innovative small molecules and biopharmaceuticals to help patients with unmet medical needs. Its North American affiliates operate in the United States and Canada as EMD Serono.
Merck Serono has leading brands serving patients with cancer (Erbitux(R), cetuximab), multiple sclerosis (Rebif(R), interferon beta-1a), infertility (Gonal-f(R), follitropin alfa), endocrine and cardiometabolic disorders (Glucophage(R), metformin); (Concor(R), bisoprolol); (Euthyrox(R), levothyroxine); (Saizen(R) and Serostim(R), somatropin). Not all products are available in all markets.
With an annual R&D expenditure of around EUR 1bn, Merck Serono is committed to growing its business in specialist-focused therapeutic areas including neurodegenerative diseases, oncology, fertility and endocrinology, as well as new areas potentially arising out of research and development in autoimmune and inflammatory diseases.
About Merck
Merck is a global pharmaceutical and chemical company with total revenues of EUR 7.1 billion in 2007, a history that began in 1668, and a future shaped by 32,458 employees in 59 countries. Its success is characterized by innovations from entrepreneurial employees. Merck's operating activities come under the umbrella of Merck KGaA, in which the Merck family holds an approximately 70% interest and free shareholders own the remaining approximately 30%. In 1917 the U.S. subsidiary Merck & Co. was expropriated and has been an independent company ever since.
For more information, please visit http://www.merckserono.net or http://www.merck.de
1. CLARITY: CLAdRIbine Tablets Treating MS OrallY
2. The McDonald criteria are diagnostic criteria for MS. In April 2001 an international panel in association with the National Multiple Sclerosis Society (NMSS) of America recommended revised diagnostic criteria for MS. They make use of advances in MRI imaging techniques and are intended to replace the Poser criteria. The new criteria facilitate the diagnosis of MS in patients who present with signs and symptoms suggestive of the disease. The McDonald criteria for the diagnosis of multiple sclerosis were revised in 2005 to simplify and speed diagnosis, while maintaining adequate sensitivity and specificity.
3. The exact correlation between MRI findings and the current or future clinical status of patients, including disability progression, is unknown.
http://www.merckserono.net
Media Relations: Tel.: +41-22-414-36-00; Merck Serono, 9 Chemin des Mines , 1202 Geneva, Switzerland

Just in case you missed it....
"which means study patients took cladribine tablets for only 8 to 20 days during the year"

Tablets taken for only 8 to 20 days of the year. Comparable to yearly infusions and certainly favorably comparible to montly infusion or daily self injections.

Thank you for all of the info. Lynn. I'll be keeping my eye on this! :)

Merck’s Multiple Sclerosis Pill Prevents Relapses (Update2)


By Naomi Kresge

Jan. 23 (Bloomberg) -- Merck KGaA, the German drugmaker seeking to be first with an oral medicine for multiple sclerosis, said its experimental pill cladribine prevented flare-ups of the debilitating neurological disease in a study.

Patients who took the pill suffered 55 to 58 percent fewer relapses, depending on the dose, than those who took a placebo during the two-year study, the Darmstadt, Germany-based company said today.

The German drugmaker said it is on track to submit an application for approval to European and U.S. regulators by the middle of this year. Merck shares climbed 5.53 euros, or 8.6 percent, to 69.89 euros in Frankfurt.

Cladribine tablets are among several oral medications for multiple sclerosis now in the final stage of clinical testing. Used to treat leukemia since the 1990s, the drug reduces the number of lymphocytes, white blood cells believed to be linked to multiple sclerosis, a disease in which the body’s immune system attacks the central nervous system. Side effects of headaches and cold symptoms were comparable in the dummy pill and cladribine patient groups, Merck said today.

Merck and Swiss drugmaker Novartis AG have said they will ask regulators in the U.S. and Europe this year to approve pills to treat the disease. Novartis released preliminary results last month showing its pill, known as fingolimod, cut relapse rates as much as 52 percent more than a standard therapy.

Side Effects

Merck already makes Rebif, one of the three beta interferons now commonly prescribed for multiple sclerosis. The injected drug, which will begin to lose patent protection in 2012, had 1.22 billion euros ($1.68 billion) in sales in 2007.

Patient advocates will be watching the long-term side effects of cladribine, which was given over a shorter time period to leukemia patients than it likely will be to multiple sclerosis sufferers, said Dr. Doug Brown, research manager for the Multiple Sclerosis Society in London, before today’s results were released. Brown said they will also want to see whether the oral medicines slow progression of the disease.

Merck and Novartis have said they will present full clinical trial results for their experimental pills at medical conferences later this year. Merck said the new study, which it funded, followed about 1,300 patients.

To contact the reporter on this story: Naomi Kresge in Zurich at nkresge@bloomberg.net
Last Updated: January 23, 2009 11:48 EST

http://www.bloomberg.com/apps/news...

This is great news, Lynn. My doctor told me that there was a pill coming that would be released within the next year or two so this must be THE ONE!!! Yippee!!!

(Wish there was something for our progressive MSr's, though, that part makes me sad).

Wow! Great news Lynn! Is this new drug safer than Tysabri? With no PML risks? That would be awesome!

I think Sandi all these new meds are very powerful & do carry risks.
This one doesnt appear to carry PML risk it carries the risk of....

Lymphopenia, an expected event based on the presumed mechanism of action of cladribine, occurred more frequently in the cladribine tablet treatment groups. With the exception of lymphopenia, the most frequently reported adverse events in the three study groups were headaches and nasopharyngitis.

*******Life with a cold in otherwords! Very irritating but better than PML

Acute nasopharyngitis is a contagious viral infection of the upper respiratory system - a form of the common cold. Symptoms include:

# Runny/stuffy nose
# Sore throat
# Dry cough
# Low Fever
# Fatigue
# Loss of appetite

Acute nasopharyngitis is spread through the air and by direct physical contact with another person who has it.

Lymphocytopenia

http://en.wikipedia.org/wiki/Lymph...

Lymphocytopenia, or lymphopenia, is the condition of having an abnormally low level of lymphocytes in the blood. Lymphocytes are a white blood cell with important functions in the immune system. The opposite is lymphocytosis, which refers to an excessive level of lymphocytes.

Lymphocytopenia may be present as part of a pancytopenia, when the total numbers of all types of blood cells are reduced.

Classification

In some cases, lymphocytopenia can be further classified according to which kind of lymphocytes are reduced. If all three kinds of lymphocytes are suppressed, then the term is used without further qualification.

* In T lymphocytopenia, there are too few T lymphocytes, but normal numbers of other lymphocytes. This is usually caused by HIV infection (resulting in AIDS), but may be Idiopathic CD4+ lymphocytopenia, which is very rare and has no known cause.

* In B lymphocytopenia, there are too few B lymphocytes, but normal numbers of other lymphocytes. This is usually caused by medications that suppress the immune system.

* In NK lymphocytopenia, there are too few natural killer cells, but normal numbers of other lymphocytes. This is very rare.

] Causes

The most common cause of temporary lymphocytopenia is a recent infection, such as the common cold.

Lymphocytopenia, but not idiopathic CD4+ lymphocytopenia, is associated with corticosteroid use, infections with HIV and other viral, bacterial, and fungal agents, malnutrition, systemic lupus erythematosus,[1] high stress levels,[citation needed] rheumatoid arthritis, and iatrogenic (caused by other medical treatments) conditions.

Lymphocytopenia is a frequent, temporary result from many types of chemotherapy, such as with cytotoxic agents or immunosuppressive drugs. Some malignancies in the bone marrow, such as leukemia, also cause lymphocytopenia.

Large doses of radiation, such as those involved with nuclear accidents or medical whole body radiation, may cause lymphocytopenia.

Diagnosis

Lymphocytopenia is diagnosed from the results of a complete blood count. In adults, a lymphocyte level below 1,500 cells/microliter is diagnostic (proof of the condition), and in children, a lymphocyte level below 3,000 cells/microliter is diagnostic.

Prognosis

Lymphocytopenia that is caused by infections tends to resolve once the infection has cleared. Patients with idiopathic CD4+ lymphocytopenia may have either abnormally low but stable CD4+ cell counts, or abnormally low and progressively falling CD4+ cell counts; the latter condition is terminal.

--------------------------------------------------------------------------------------

And of couse to added it to an existing MS treatment Rebif. We have been through this before :( Not fond of those combination therapies.

The ORACLE MS (ORAl CLadribine in Early MS) study: a two-year Phase III placebo-controlled trial designed to evaluate the efficacy and safety of cladribine tablets as a monotherapy in patients at risk of developing MS (patients who have experienced a first clinical event suggestive of MS). This trial was announced in September 2008.

- The ONWARD (Oral Cladribine Added ON To Rebif New Formulation in Patients With Active Relapsing Disease) study

: a Phase II placebo-controlled trial designed primarily to evaluate the safety and tolerability of adding cladribine tablets treatment to patients with relapsing forms of MS, who have experienced breakthrough disease while on established interferon-beta therapy. This trial was announced in January 2007.

Thanks Lynn! Your info is outstanding!

Thank you very much, Lynn! This is great news and I am hoping that they do actually speed this up with the FDA fast track approval. Your information, research and links are invaluable. One thing I didn't see was anything on the proposed cost of cladribine in any of the links. Did I just miss it or was it not there?

Thanks again for everything, Rebecca

I had not heard of this drug before. It seems like great news. With this, and Fingolimod, the trial I am currently on and which may be on the same FDA track shortly after this one, it would seem that we will all start having as many oral medication options as we currently have injectables. Great news all around. Thanks, Lynn!