EDITORIAL COMMENTARY

August 1, 2008

As many of you know, and believe me, I am not patting myself on the back, I was an early opponent of Tysabri and was early in predicting the removal of Tysabri from the market in 2005.

As many of you also know, I was vehemently opposed to the FDA's decision to approve Tysabri, for re-introduction in the U.S., even with the so-called "black box label." The fact that European drug agencies had approved the drug for the treatment of multiple sclerosis (MS) did not provide me any comfort.

Please, please, take note of the following press release from Biogen-Idec and Elan, manufactures/marketers of Tysabri:

http://www.bloomberg.com/apps/news?pid=conewsstory&refer=conews&tkr=BIIB:US&sid=a40u7vb1OLaw

In short, progressive multifocal leukoencephalopathy has now been found among a small number - very small at this point - of patients taking the drug for MS. Many prominent neurologists - many whom I deeply respect - have been supporters of this "treatment." Again, despite this, I have remained adamantly opposed to the use of this drug.

Why? I am sorry. But the risk of developing a deadly brain virus, even if the manufacturers quantify the risk at very low percentages, just seems a bit too HIGH for me relative to a) the fact that MS, itself, is not deadly, and b) there are other options. AND, while those options are not yet perfect, there are several new drugs in late stage clinical trials, including oral medications, that so far are proving far more effective in treating MS.

Biogen-Idec and Elan state that they have no intention of voluntarily pulling Tysabri from the market - once again.

As the news report from Bloomberg, a major business news sources, reports, the companies still plan to have 100,000 people on Tysabri by 2010. However, as of today, the stock market has made the assumption, by dropping the prices of the stocks, that the market for Tysabri will soon evaporate. As, in my humble opinion, it should.

For far too long, people with MS and others diseases, have been used as a guinea pig population, with the FDA permitting companies to rush new compounds to market. There is a trade-off here. I understand that. People want treatments. They want effective treatments. Many people that suffer from diseases such as MS want new treatments because they feel increasingly feel frustrated - and rightly so (being one of them) - with the persistent march of their illnesses and the negative impacts on the quality of their lives.

I understand all of that. I also understand that two pharmaceutical companies, Merck and Pfizer, that have performed clinical trials on very inexpensive drugs - statins - for the potential treatment of MS, seem to have no interest in pursuing the MS market with those soon-to-be off patent protection Pfizer's Lipitor), or already off patent protection (in the case of Merck's Zocor/simvastatin) drugs. After all, the MS market is far more lucrative if you can offer a new drug for $2,000 - $4,000 monthly instead of $23 - $100 a month. Keep in mind, in the U.S., there are only about 400,000 known cases of MS. So it's not a huge market.

I hope that you can take time to pass this Tysabri news on to people that may be interested.

Let me see. The possibility of death vs. living with MS. For me, however small the risk of progressive multifocal leukoencephalopathy, I will happily live with MS.

Sincerely,

Cary J. Polevoy

Teva Pharmaceutical's Altered Peptide Ligand Copaxone Boasts the Greatest Patient Share Among First- and Second-Line Therapies for the Treatment of Mu

WALTHAM, Mass., March 11 /PRNewswire/ -- Decision Resources, one of the world's leading research and advisory firms focusing on pharmaceutical and healthcare issues, finds that Teva Pharmaceutical's Copaxone has the greatest patient share among first- and second-line therapies, and falls short of Merck Serono/Pfizer's Rebif (by 0.2 percent) in third-line treatment. However, in all three lines of therapy, the interferon-beta drug class (Biogen Idec's Avonex, Rebif, and Berlex's Betaseron) outpaces the altered peptide ligand drug class (consisting only of Copaxone) in patient share. Competition between the two drug classes is fiercest in first-line therapy.

"The low volume of patient share attributed to Avonex or Rebif compared with Copaxone in first- and second-line treatment illustrates a significant delay on the part of physicians and/or patients to engage in an interferon- beta therapy within a year of a patient's initial diagnosis for multiple sclerosis," said Madhuri Borde, analyst at Decision Resources. "However, the magnitudes of Rebif's first- and second-line patient shares suggest that some physicians are treating the disease more aggressively than might be expected, as this high-dose, high-frequency agent reaches patient shares close to and surpassing Avonex in first- and second-line treatment, respectively."

According to the new report entitled Treatment Algorithms in Multiple Sclerosis, neurologists note that Copaxone's better short-term and long-term side-effect/safety profile, together with its lower rate of induction of neutralizing antibodies, are critical reasons for choosing Copaxone instead of Avonex, Rebif and Betaseron. Although Copaxone is administered daily, 23-28 percent of neurologists we surveyed indicate that a key reason to prescribe the drug over any of the interferon-beta therapies is the drug's ability to foster greater patient compliance, an attribute that is closely tied to the Copaxone's lower incidence of flulike side effects.

About Treatment Algorithm Insight Series
Decision Resources combines in-depth primary research with the most extensive claims-based longitudinal patient-level data from PharMetrics(R) to provide exceptional insight into physicians' prescribing trends and the factors that drive therapy product choice, from diagnosis through multiple courses of treatment, for a specific disease.

For each disease examined, Decision Resources' Treatment Algorithm Insight Series provide the following:

-- Summary of U.S. medical practice based on interviews with leading experts in the field. -- Qualitative diagnosis/referral/treatment algorithm for the United States. -- Drug usage by lines of therapy (1st, 2nd, 3rd line). -- Discussion of key freeform combinations by lines of therapy. -- Product share (class and specific compound level) within each line of therapy (1st, 2nd, 3rd line). -- Progression of therapy from key 1st line products. -- Pathway to key therapies from previous therapies. -- Qualitative analysis of two-year forecast incorporating upcoming launches, changes in reimbursement, etc.

About Decision Resources
Decision Resources, Inc., (http://www.decisionresources.com/) is a world leader in healthcare market research publications, advisory services, and consulting designed to help clients shape strategy, allocate resources, and master their chosen markets.
All company, brand, or product names contained in this document may be trademarks or registered trademarks of their respective holders.

For more information, contact: Elizabeth Marshall Decision Resources, Inc. 781-296-2563 emarshall@dresources.com
Decision Resources

Interferon Beta-1a and Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis: Presented at ECTRIMS

By Chris Berrie

PRAGUE, CZECH REPUBLIC -- October 16, 2007 -- Interferon beta-1a (IFNbeta-1a) has no significant efficacy benefits or safety issues over the polypeptide glatiramer acetate for patients with relapsing-remitting multiple sclerosis (RRMS), according to results from a multicentre, randomised, comparative, assessor-blinded, open-label trial.

Principal investigator Dan D. Mikol, MD, PhD, Associate Professor of Neurology, Department of Neurology, University of Michigan, Michigan, United States, presented the findings here on October 14 at the 23rd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS).

This was the first head-to-head study of IFNbeta-1a and glatiramer acetate.

"The planned sample size was 736 patients, and included in the expectations was that there would be an 80% power to detect a 30% difference between these two agents in the primary outcome, which was time to first relapse."

Dr. Mikol and colleagues enrolled 764 patients aged 18 to 60 years and diagnosed with relapsing-remitting MS by McDonald criteria, had experienced one or more attacks within the prior 12 months, and were clinically stable or had improving neurological state in the prior 4 weeks. They also had magnetic resonance imaging (MRI) evidence of brain lesions and an expanded disability status scale (EDSS) of 0 to 5.5.

Following prestudy evaluation, 386 patients were randomised to 44 mcg of subcutaneous IFNbeta-1a three times weekly and 378 patients to 20 mg of subcutaneous glatiramer acetate once daily, both for 96 weeks.

Key baseline clinical characteristics in the two treatment groups were similar for time since first relapse (5.93 years, 6.55 years, respectively), number of T1 Gd-enhancing lesions (1.47, 1.65), T1 Gd-enhanced lesion volume (254.81, 241.99 mm3), and T2 lesion volume (7915.61, 7560.38 mm3).

However, 60% of patients in the interferon arm had more than one relapse in the previous 24 months compared with 71% in the glatiramer acetate arm, Dr. Mikol noted.

The primary endpoint was time to first relapse; the predefined secondary endpoints were mean number of T2 active (new or enlarging) lesions per patient per scan, and mean number of T1 Gd-enhancing lesions per patient per scan.

Tertiary endpoints were: mean number of combined unique active (CUA) lesions per patient per scan, and proportion of scans per patient with CUA lesions; clinical assessment of relapse rate, and proportion of patients free of relapses.

For the primary, secondary and some of the tertiary analyses, results were also stratified by prespecified subgroups.

At 96 weeks, the researchers found no significant differences between the IFNbeta-1a and glatiramer acetate treatment arms in terms of the primary outcome (hazard ratio [HR], 0.943; 95% confidence interval [CI], 0.74-1.21; P =.643). Dr. Mikol noted that these two patient groups experienced 45% fewer relapses than expected.

Due to this slow relapse rate, the researchers included a series of prespecified subgroup analyses relating to baseline T1 Gd-enhancing lesions (0 vs >=1), relapses 2 years prior to baseline (1 vs >=2), geographic region (non-Russia vs Russia), EDSS at baseline (<=median 2.0 vs >median 2.0), baseline T2 lesion volume (<=median 3707.5 vs >median 3707.5 mm3), and MS therapy in the prior 6 months (e.g. steroids; no vs yes).

The only subgroup where the researchers found a significant difference at the 96-week evaluation was EDSS at baseline in favor of IFNbeta-1a (n = 207) over glatiramer acetate (n = 211) in the group with EDSS scores below the median (HR, 0.648; 95% CI, 0.45-0.94; P =.022)

Although the researchers observed no significant difference between IFNbeta-1a and glatiramer in the number of T2 active lesions per patient per scan (0.7 vs 0.8; P =.178), within the prespecified subgroup analyses, they found significantly fewer T2 active lesions in patients treated with IFNbeta-1a both in the subgroup of patients with EDSS scores lower than the median (P =.035) and in non-Russian patients versus Russian patients (P =.043).

Significant benefit in favor of IFNbeta-1a versus glatiramer was seen for the secondary endpoint of T1 Gd-enhancing lesions (0.2 vs 0.4; P <.001) and for mean CUA lesions per patient per scan (0.9 vs 1.2; P =.010). Within the subgroups, IFNbeta-1a was better than glatiramer in patients who were non-Russian (P <.001), had baseline scores that were lower than the median on the EDSS (P <.001), with baseline lesion volume greater than the median (P <.001) and had prior MS therapy (P <.001).

For the tertiary endpoints of mean number of CUA lesions/patient/scan, and proportion of scans/patient with CUA lesions, these both indicated significant benefit for IFNbeta-1a, with mean treatment differences of -0.31 (P =.010) and -5.9 (P =.009), respectively.

Finally, for the annualized relapse rates for IFNbeta-1a and glatiramer acetate, there were no significant differences between these two treatment groups (0.30 vs 0.29; P =.828). "What is intriguing and certainly stands out in this trial is the fact that the relapse rate on-study was so low, 0.3, which is certainly much lower than was anticipated and is different to what has been seen in previous clinical trials," added Dr. Mikol.

Thus Dr. Mikol summarized, "There were no significant difference in primary endpoint of time to first relapse; the safety outcomes were consistent with the known profiles of both treatments; and there was significant difference in favor of IFNbeta-1a for T1 Gd-enhancing lesions and for some of the additional pre-specified subgroup analyses.

Funding for this study was provided by Merck Serono International S.A. and Pfizer Inc.


[Presentation title: The REGARD Trial: A Randomised Assessor-Blinded Trial Comparing Interferon Beta-1a and Glatiramer Acetate in Relapsing-Remitting Multiple Sclerosis. Abstract 119]