The 23% lower annual relapse rate among the laquinimod patients versus the placebo ones is “statistically significant”, the researchers said. There was also a 36% reduction in disability progression as measured by Expanded Disability Status Scale, and 33% less brain atrophy among the laquinimod participants.

View full article here: http://www.mscare.org/cmsc/Informs-Glatiramer-Acetate-data.html

According to the press release, Teva will vigorously defend its COPAXONE® intellectual property rights against infringement wherever they are challenged and intends to pursue all relevant regulatory avenues via the FDA. Teva’s lawsuit has been filed within the 45-day period provided under the Hatch-Waxman legislation and will triggers a stay of FDA approval for the Mylan ANDA until the earlier of the expiration of a period of 30 months or a district court decision in favor of Mylan.

According to Teva, COPAXONE® is a highly-complicated product to develop and manufacture, and given the inability to fully characterize the active ingredients of COPAXONE®, the company doubts any generic applicant’s ability to demonstrate conclusively that the composition of its product is identical to that of COPAXONE®. In fact, Teva contends that any company that files an application for any glatiramoid substance, via an ANDA or 505(b)(2) application, should conduct full-scale, placebo-controlled clinical trials with measured clinical endpoints in MS patients to establish safety, efficacy and immunogenicity in this patient population. Internal research at Teva has indicated that even minor changes in the synthetic process and/or molecular weight distribution of a glatiramoid can have severe ramifications on the safety and mechanism of action of the product.

The patents covering COPAXONE® all seem exceptionally similar, which is not to be unexpected. The earliest patent, which appears to be the parent that spawned the others, explains that COPAXONE® is a drug used to treat multiple sclerosis, and is an apparently a significant improvement on the prior art. The patent explains:

Copolymer-1 is a synthetic polypeptide analog of myelin basic protein (MBP), which is a natural component of the myelin sheath. It has been suggested as a potential therapeutic agent for multiple sclerosis (Eur. J. Immunol. [1971] 1:242; and J. Neurol. Sci. [1977] 31:433). All references cited herein are hereby incorporated by reference in their entirety. Interest in copolymer-1 as an immunotherapy for multiple sclerosis stems from observations first made in the 1950’s that myelin components such as MBP prevent or arrest experimental autoimmune encephalomyelitis (EAE). EAE is a disease resembling multiple sclerosis that can be induced in susceptible animals.

Copolymer-1 was developed by Drs. Sela, Arnon, and their co-workers at the Weizmann Institute (Rehovot, Israel). It was shown to suppress EAE (Eur. J. Immunol. [1971] 1:242; U.S. Pat. No. 3,849,550). More recently, copolymer-1 was shown to be beneficial for patients with the exacerbating-remitting form of multiple sclerosis (N. Engl. J. Med. [1987] 317:408). Patients treated with daily injections of copolymer-1 had fewer exacerbations and smaller increases in their disability status than the control patients.

Copolymer-1 is a mixture of polypeptides composed of alanine, glutamic acid, lysine, and tyrosine in a molar ratio of approximately 6:2:5:1, respectively. It is synthesized by chemically polymerizing the four amino acids forming products with average molecular weights of 23,000 daltons (U.S. Pat. No. 3,849,550).

It is an object of the present invention to provide an improved composition of copolymer-1.

The Israel based Teva Pharmaceutical Industries Ltd. is among the top 20 pharmaceutical companies in the world and perhaps the leading generic pharmaceutical company in the world, which is in itself ironic. COPAXONE® sales totaled $2.3 billion in 2008, accounting for over 20% of total revenues for Teva. Moving forward COPAXONE® was expected to account for an even larger percentage of Teva’s revenues. Presently Teva pays French drug company Sanofi-Aventis royalties even though Teva is solely responsible for marketing in North America. Teva must pay Sanofi-Aventis royalties into 2010 as a result of a deal between the companies dating back to April 2008. Thus, at a time when COPAXONE® was to become far more important to Teva it would be potentially devastating to the company to face generic competition. For now at least Teva will enjoy the market to itself, at least for the next 30 months.

View full post here: http://www.ipwatchdog.com/2009/10/18/teva-sues-mylan-over-multiple-sclerosis-drug-copaxone%C2%AE/id=6712/

The treatment, glatiramer acetate, marketed as Copaxone, was tested in 16 countries among 481 patients with a telltale lesion in the central nervous system called clinically isolated syndrome.

The volunteers either received the drug or a dummy lookalike for up to three years.

Copaxone reduced the risk of developing “clinically definite” MS by 45 percent compared with a placebo.

In addition, the time it took for 25 percent of patients to develop the full-scale disease was more than doubled in the Copaxone group, at just under two years on average compared with just under one year in the placebo group.

Around a million people around the world are affected by MS, a degenerative disease in which the immune system attacks myeline, the fatty sheath that protects nerve fibres.

As a result, signals between nerve cells are delayed, disrupted or even blocked, rather like a poor connection in an electrical wire.

This causes worsening problems in coordination and balance, as well as blurred vision and slurred speech.

“This study establishes glatiramer acetate as an option for patients with clinically isolated syndrome who choose to start treatment early to improve control of the underlying disease process,” says the new paper.

The study was led by Giancarlo Comi, a professor of neurology at Milan’s Vita-Salute University in Italy.

Copaxone is currently approved for treating “relapsing-remitting” forms of MS.

View full article here: http://www.google.com/hostednews/afp/article/ALeqM5hMp9AsbapJMeUGkb-ZYv457bhy4w

Bravo is a global clinical trial designed to evaluate the efficacy, safety and tolerability of laquinimod compared to placebo, and to provide risk-benefit data for laquinimod compared to a currently available injectable treatment, Avonex.

The Bravo study completed patient enrollment in June 2009, recruiting more than 1,200 patients at 156 sites in the US, Europe, Israel and South Africa.

Allegro, the first global Phase III trial of laquinimod, completed enrollment in November 2008, after recruiting more than 1,000 patients at 152 sites in North America, Europe and Asia, said Teva. The trial is currently ongoing.

Moshe Manor, Teva’s group vice president of global branded products, said: “Teva and Active Biotech are encouraged by the potential of laquinimod to address patients’ unmet need for an oral immunomodulating multiple sclerosis therapy that provides efficacy while maintaining safety. We look forward to continuing our clinical Phase III program of laquinimod, and hope it will offer enhanced quality of health for relapsing-remitting multiple sclerosis patients.”

View full article here: http://www.tmcnet.com/usubmit/2009/06/26/4246746.htm

JERUSALEM–New data presented today provided evidence that long-term treatment with COPAXONE^® (glatiramer acetate injection) may offer sustained protection from neuronal/axonal injury. This protective effect was reflected biologically by a significant increase in N-acetylaspartate (NAA), a specific marker of neuronal mitochondrial function, in treated versus non-treated relapsing-remitting multiple sclerosis (RRMS) patients. These six-year results augment previously published findings suggesting that treatment with COPAXONE^® may provide a neuroprotective effect in RRMS patients^{1, 2}.

The study, “Six-Year Prospective Multi-Voxel Brain MRS Study of Two Cohorts in RRMS To Examine the Effect of Glatiramer Acetate on Neuronal/Axonal Metabolic Injury,” is the largest (n=46) and longest study of its kind to date. In the study, patients taking COPAXONE^® for six years experienced an improvement in neuronal mitochodrial function, as quantified by an increase in neuronal NAA levels and evaluated by ¹H- Magnetic Resonance Spectroscopy (¹H-MRS). Decreased neuronal NAA levels are reflective of neuronal/axonal injury.

“The potential ability to prevent or repair brain tissue damage in RRMS patients is an important treatment consideration given the degenerative pathology of this life-long condition,” said Omar Khan, M.D., Professor of Neurology, Director, Multiple Sclerosis Center, Wayne State University and lead investigator of the study. “These data further substantiate our previous research into the potential neuroprotective effect of COPAXONE^®, as well as the use of NAA measures as a reliable marker for assessing a patient’s disease progression and response to treatment.”

Similar results were reported from a different study examining the effect of COPAXONE^® in Clinically Isolated Syndrome (CIS) patients. The study demonstrated patients who received COPAXONE^® improved in their cerebral neuroaxonal integrity relative to patients treated with placebo. Patients on placebo showed a decline in NAA consistent with that demonstrated in historical control studies.

About the Study

Forty-nine patients, divided into two cohorts of previously treatment-naïve RRMS patients, underwent serial brain ¹H-MRS scanning. Group 1 (n=22) included patients who started COPAXONE^® therapy at enrollment (n=18) and during the course of the study (n=4). Mean age, disease duration and Expanded Disability Status Scale (EDSS) were 43.5 years, 8.2 years and 2.77, respectively. Mean NAA/Cr at baseline was 1.97 + 0.24 and 2.20 + 0.16 (+11.6 percent) at year 6 (p<0.05). Group 2 (n=31) included patients who started GA therapy at enrollment. Mean age, disease duration and EDSS were 35.1 years, 5.8 years and 2.53, respectively. Mean NAA/Cr at baseline was 1.99 + 0.1 and 2.12 + 0.08 (+6.53 percent) at year 6 (p<0.05). Twelve untreated RRMS patients were also scanned for two years and showed a significant decline in NAA/Cr over the two years of follow-up. Additionally four untreated patients initiated COPAXONE^® during the course of the study and demonstrated considerable improvement in the mean NAA/Cr ratio, as well as clinical stability during total study observation. Finally, nine healthy volunteers were scanned annually for controls. Further analysis is ongoing. The study was in part supported by Teva Neuroscience.

Read full article here: http://www.businesswire.com/portal/site/google/?ndmViewId=news_view&newsId=20090428005745&newsLang=en

Oral cladribine (EMD Serono) reduced the relapse rate significantly more than inactive placebo in the phase 3 “CLARITY” study of 1,326 people with relapsing-remitting MS. These initial results – the first from any phase 3 study of oral therapy for MS — are reported in a press release from EMD Serono dated January 23, 2009. Additional study results will be submitted for presentation at an upcoming scientific meeting. Oral cladribine has been designated by the U.S. Food and Drug Administration as a “Fast Track Product,” which should expedite its future review. The company plans to file for FDA approval of oral cladribine in mid-2009.

Background: Cladribine can interfere with the activity of white blood cells that underlie the immune attacks that cause the unpredictable symptoms of MS. Injectable cladribine is used to treat hairy cell leukemia. Studies have suggested a benefit in MS. In addition to the completed CLARITY study, other ongoing studies of oral cladribine funded by EMD Serono include:
• The ONWARD study, an investigation of the safety and effectiveness of adding high or low doses of oral cladribine to interferons in a trial recruiting 260 people with relapsing forms of MS (this study is currently recruiting participants); and
• The ORACLE MS study, designed to evaluate the safety and effectiveness of oral cladribine in people who have experienced a neurological episode that puts them at risk for developing MS (this study is currently recruiting participants).

The CLARITY Study: For the first year of the study, 1,326 participants were randomly assigned to receive a low dose of cladribine (two treatment cycles per year, each cycle consisting of one tablet per day for four to five consecutive days), a high dose (four cycles) of cladribine, or inactive placebo. In the second year, both treatment groups received a low dose of cladribine. The primary endpoint was the drug’s effect on relapse rate at two years compared with placebo. Secondary endpoints included effects on disease activity, as detected by MRI scans, the proportion of relapse-free participants, and disability progression.

The relapse rate was reduced significantly more than placebo in both treatment groups (by 58% in the low-dose group and by 55% in the high-dose group). The company reports that secondary endpoints of the CLARITY study were also met, although the details of these are not provided in the press release. Additional study results will be submitted for presentation at an upcoming scientific meeting.

Lymphopenia – a reduction of white blood cells – was the most frequent adverse event, and occurred more frequently in the groups on cladribine. Other adverse events reported in all three groups were headaches and cold symptoms.

“These are exciting initial results, and we look forward to seeing the full data,” says John Richert, MD, Executive Vice President of Research and Clinical Programs at the National MS Society. “If this pill proves to be safe and effective for people with relapsing MS, it represents a major treatment breakthrough – hopefully the first of many more in the pipeline.”

View full post here: http://www.nationalmssociety.org/news/news-detail/index.aspx?nid=650

Teva’s laquinimod for MS gets fast tracked
February 12, 2009 — 3:34pm ET | By Calisha Myers

Israel-based Teva Pharmaceutical announced today that the FDA has granted the Fast Track designation to laquinimod, its investigational treatment for relapsing-remitting multiple sclerosis (RRMS). Laquinimod is a once-daily treatment administered orally. Teva licensed the compound from Swedish developer Active Biotech in 2004.

The first phase III clinical trials–Allegro–were completed in November 2008 and Teva is now enrolling patients globally for Bravo, the second Phase III study. Teva said that with the FDA’s decision, the drug could enter the market as soon as late 2011. “We are pleased that the FDA has awarded laquinimod with a Fast Track designation, and are hopeful it will be part of our growing portfolio of innovative therapies,” Moshe Manor, Vice President, Global Innovative Resources Group at Teva, said in a statement.

Shares of Teva rose 75 cents to $43.88 in afternoon trading on Thursday, while Active Biotech’s shares jumped $3.40 to $38.30.

ALSO: It seems that Teva is trying to make 2009 the year of generics. The company’s new campaign, “Year of Affordable Healthcare,” employs social media–including YouTube, Twitter and possibly Second Life– and various other tools to build its largest ever PR campaign. Teva tells PRWeek that 2009 is “a critical year for the future of both healthcare in America and the generic drug industry.” Report