Fingolimod ( Gilenia) By Novartis

Novartis has come up with oral therapy of MS. This is Gilenia ( Fingolimod; FTY 720). I had reported earlier in my blog about these Chinese fungus extract. This drug is in priority review status with FDA ( USA). Novartis through its clinical trial studies claims that once daily dose of 0.5 mg of Gilenia reduces the frequency or relapses, disability progression and lesions in the brain in RR-MS cases.

If the drug has the efficacy as claimed by the company than its a boon for the MS patients world over. It is to be seen whether FDA approves the drug for marketing....

Reference

http://www.novartis.com/newsroom/media-releases/en/2010/1386852.shtml

MS not autoimmune but vascular disease

Dr. Paolo Zamboni (Professor of Medicine, Univ. of Ferrara, Italy) has made a breakthrough by changing the basic understanding of MS. MS is considered as an autoimmune disorder that leads to damage of myelin in the CNS. However, according to Dr. Zamboni's research MS is a vascular disease (blood vessel are the source of problem). The heavy iron deposits were damaging the blood vessels draining the brain. This situation he calls " Chronic cerebrospinal venous insufficiency (CCVI)".This in turn is the reason for inflammation and cell death in the CNS. He therefore, hypothesized that by clearing the clogged vessels could stop progression of MS. He performed a surgery on his wife (a MS patient) similar to angioplasty where an inflated balloon is used to clear the blood vessels. His wife, who had the surgery 3 years ago, has not had an attack since.

If this is true then no doubt it will become very simple to treat MS and may even prevent MS!

http://www.theglobeandmail.com/news/national/researchers-labour-of-love-leads-to-ms-breakthrough/article1372414/
http://www.ctv.ca/servlet/ArticleNews/story/CTVNews/20091120/W5_liberation_091121/20091121?s_name=W5

Review of Transfer Factor for MS

Recently, I completed a review of descriptions of Transfer Factor. Here's my summary:

Resources Reviewed:
1. Two NIH papers on clinical trials:

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1537193

http://www.ncbi.nlm.nih.gov/pubmed/3555898


2. Sites calling this a “quack”:

http://briandeer.com/wakefield/transfer-factor.htm

http://www.quackwatch.com/01QuackeryRelatedTopics/ms.html

3. The 4life site - http://www.transferfactorinstitute.com

4. Memorial Sloan-Kettering Cancer institute site - http://www.mskcc.org

Based on the above readings, we currently don’t have enough information to call it effective for Multiple Sclerosis. The clinical trials (involving blindfold recipients) published with transfer factor alone or in conjunction with interferon-beta showed no difference from the untreated group. Thus the positive aspect of these trials is that no side effects of transfer factor were noted in the participants. In other words, they report that patients were not harmed by taking this drug during the trials.

In fact, if you read the Sloan- Kettering Cancer Institute site, it claims that transfer factor is not effective against many other autoimmune disorders including MS whereas they did term it effective against some immune disorders. Moreover, I could not find any international paper published describing the mode of functioning ("how it works") of Transfer Factor on the internet. Hence how this factor will modulate the immune problem in MS is questionable based on the above. I have not come across any new report on transfer factor and MS on the internet.

It is possible that the above conclusions can change with new data.

Ultimately, as always, the decision of taking this medicine lies with the person and her doctor.

Results of Phase II Trials by Novartis of FTY 720 (fingolimod)

1. A Phase II clinical trial involves a larger group of people ( 20- 300) to know how well the drug works and also to continue to test the safety levels of the drug (already done in Phase I trials).

2. Oral doses of FTY720 given as once a day pills of 5mg and 1.25 mg to 2 groups ( 281 patients per group) of relapsing remitting MS patients. The treatment was carried out for 3 years. This study was done in Canada and 10 European countries.

3. This trial gave positive results.

4. After 2 years of study 77% (5mg) and 75% (1.25mg) patients showed reduced rates of annual relapses of MS. The first 6 months trial showed a decrease of 50% in the treated patients compared to 30-35% decrease by the present therapies (first line treatments).

5. "On the basis of comparable efficacy and better safety profile" all the patients were shifted to 1.25mg dose of FTY720.

6. Three year data showed that 89% of the patients got free of active brain lesions which are seen in untreated MS patients as tested by MRI scans.

7. Side Effects - FTY720 was well tolerated in patients in 3 years. However, it showed the following side effects in 16 % of treated patients: Nasopharyngitis (inflammation of nasal passage and upper part of pharynx), fatigue, headache, influenza increase in liver enzyme levels ( alanine aminotransferase). Also, a small number of patients showed localized skin malignancies.

More on ALT- An ALT (alanine aminotransferase test) is done with blood samples to determine the liver damage. Therefore increased levels of ALT indicate some damage to liver.

So what is not clear from the Novartis report is which dose of FTY720 is causing the liver damage and to what extent? may be this is the reason for the shift from 5mg to 1.25 mg dose of FTY720.

8. Novartis is continuing with two very large Phase III clinical trials. They will also do regulatory filings by end 2009. However that does not mean that approval for sale is ensured.

Personal view- there is no harm in keeping a track of this drug for another year. It sounds promising. However, till FDA approval is obtained, nothing can be decided about it. It is very important that the dose and safety levels of the drug is thoroughly established. Immunomodulators and immunosuppressant drugs show very strong positive results very quickly but fail at safety levels.

References:

1. Novartis Press Release

2. Webmd Reference

Isaria sinclairii / FTY720 ( fingolimod) - A Chinese "medicine" for Multiple Sclerosis

This fungus grows on insects and devours them. It belongs to a group of fungi commonly called ' vegetable wasps and plant worms'. Specifically, Isaria has been used in chinese medicine for centuries. There are numerous pictures of this fungi posted on the web. Here's one from http://botit.botany.wisc.edu/toms_fungi/jun2006.html

I read two pharmacology research papers about Isaria that indicate following information:

1. A chemical compound called FTY720 was extracted from Isaria by a Japanese group in 2000.

2. This FTY720 has been found to be an immunomodulator. This means it has an effect on the immune system (both stimulation or suppression).

3. Experiments have shown that FTY720 makes majority of white blood cells ( mainlyT and B cells) move into the lymph nodes from the general circulation ( this known as 'homing' of WBCs).

4. This action of FTY720 doesn't effect RBcs and other WBCs.

5. T cells ( specially CD4+ types) are one of the main culprits of myelin damage in the Central nervous system.

6. This compound has been put to clinical trials for MS. The phase 2 trial shows that the FTY720 treated MS patients had a lower relapse rate in a year compared with non-treated MS patients. According to that review, FTY720 showed very promising results.

7. There are phase 3 trials being conducted to prove the effectiveness of this compound.

8. Also note that MS patients that took FTY720 showed some side effects like- slowing a heart beat, nausea, headache and an upset stomach.

9. Novartis is going to file for its regulation as an MS drug by end 2009 (www.pharma.us.novartis.com/newsroom/press-release.jsp?...) www.novartis.com/newsroom/media-releases/en/.../1344775.shtml ).

References:

1. http://www.cell.com/trends/pharmacological-sciences/abstract/S0165-6147(02)00012-3

2. http://pharmrev.aspetjournals.org/content/60/2/181.abstract

Dr. Ratna Mirchandani's research in one post

It's always a challenge to summarize one's research for a lay audience, but without this, we risk being guilty of not communicating. Here is a summary of my work for the non-biologist.

Multiple Sclerosis is an inflammatory disease. Inflammation is the critical aspect of MS. During MS, inflammation affects the central nervous system (brain, spinal cord) in many ways. Controlling it can dramatically reduce the damage done by MS.

Statins are a popular class of drugs used for cholestrol control and for other conditions. My advisor, Dr. Singh, decided to explore the use of Statins to help cure MS. If this worked, we could speed up a remedy to help millions of patients. It would also be cheaper to use an existing, proven drug instead of developing a new one from scratch. The economics of this approach are compelling. What remains is the science. This is hard.

We tested Statins in an animal model of MS called EAE. This gave us useful insight into the possible pathways that could be controlled by Statins to reduce inflammation.

We got the insight. Now what?

After many other reports about various Statins being useful in animal and cell models, some have been taken for Clinical Trials for possible use by patients. That is where we are in the exploration of the use of Statins to reduce the suffering caused by MS.