Posted by: Thixia | June 26, 2008

Laquinimod Oral Drug for MS

Laquinimod is a novel once-daily, orally administered immunomodulatory compound developed as a disease modifying treatment for multiple sclerosis (MS).

 

 

Laquinimod shows great promise in Multiple Sclerosis trial

 

Laquinimod, a new type of immumodulatory agent for relapsing-remitting multiple sclerosis, led to a 40% reduction in lesions, according to results of a multicenter, placebo-controlled phase IIb trial.

Patients treated with laquinimod at a dose of 0.6 mg a day averaged 2.6 gadolinium-enhancing lesions on MRI compared with 4.2 for the placebo group (P=0.0048) as reported by Giancarlo Comi, M.D., of the University Vita-Salute and colleagues in the June issue of The Lancet.

The between-group difference emerged early in the trial, and follow-up beyond the primary study period demonstrated even larger reductions in MRI-detected lesions with laquinimod versus placebo.

Additionally, the number of new lesions was reduced by 50% in the laquinimod group.

“The decrease of MRI activity during the last part of the study was evidence for both gadolinium-enhancing and new T2 lesions, indicating that laquinimod reduces not only the extent of blood-brain barrier opening, but also the accrual of fixed lesions,” the authors said.

Available therapies for multiple sclerosis all target inflammatory aspects of the disease. In addition, all of the approved therapies require injection, creating a potential advantage for any oral agent.

Laquinimod is structurally related to linomide, a drug that reduced disease activity in MS but had unacceptable toxicity, the authors said. Preclinical and phase I clinical studies suggested laquinimod had greater activity and a more favourable safety profile compared with linomide.

In a previous 24-week, randomized phase II study, laquinimod 0.3 mg/d suppressed formation of new MS lesions and was well tolerated. Those results led to the current evaluation of two different doses of the drug.

The study involved 306 patients relapsing-remitting multiple sclerosis with who had had one or more relapses in the previous year and at least one gadolinium-enhancing lesion on screening MRI. Investigators at 51 centers in nine countries randomized the patients to placebo or to laquinimod 0.3 mg/d or 0.6 mg/d.

The trial lasted 36 weeks, and the primary outcome was the cumulative total of gadolinium-enhancing lesions from the final four MRI scans at weeks 24, 28, 32, and 36.

Compared with placebo, laquinimod 0.6 mg reduced the average number of lesions per scan on the final four MRI scans by 40.4%.

The 0.3 mg dose did not significantly reduce the number of lesions compared with placebo (3.9 versus 2.6).

Comparison of the median cumulative number of lesions from the last four MRI scans resulted in a 55% reduction in the number of lesions with laquinimod 0.6 mg versus placebo (4.0 versus 9.0).

The number of new T2 lesions on the last four scans was 44% lower with laquinimod 0.6 mg (P=0.0013), and the number of new T1-hypointense lesions was 51% lower in the laquinimod 0.6 mg group (P=0.0064).

Examination of MRI scans from weeks 12 through 36 demonstrated a 51% reduction in the mean number of gadolinium-enhancing lesions with laquinimod 0.6 mg (2.7 versus 4.4) and a 60% decrease in the median number of lesions (6.0 versus 15.0).

Patients in the laquinimod 0.6 mg group had an annualized relapse rate of 0.52 compared with 0.77 for those on placebo which was not statistically significant (P=0.0978). Additionally, 70.8% of laquinimod 0.6 mg patients were relapse-free compared with 62.7% of the placebo group.

Both doses of laquinimod were well tolerated.  The primary treatment-related effect was a transient, dose-related increase in liver enzymes, the authors said.

Source: The Lancet – Comi G, et al “Effect of laquinimod on MRI-monitored disease activity in aptients with relapsing-remitting multiple sclerosis: a multicenter, randomized, double-blind, placebo-controlled phase IIb study” Lancet 2008; 371: 2085-2092. (20/06/08)

 

Initiation of Enrollment in Pivotal Phase III Clinical Study of Oral Laquinimod for Relapsing-Remitting Multiple Sclerosis

 

Teva Pharmaceutical Industries Ltd. and Active Biotech AB announced today the initiation of enrollment in the Allegro trial (assessment of oral laquinimod in preventing progression of multiple sclerosis). Allegro is a global pivotal, 24/30-month, double-blind, Phase III study designed to evaluate the efficacy, safety and tolerability of the oral investigational compound laquinimod versus placebo in the treatment of relapsing-remitting multiple sclerosis (RRMS). The Allegro trial aims to enroll approximately 1,000 patients with RRMS.

“Currently there are several RRMS treatments available; however, they are all administered via injection or infusion. An orally administered therapy brings us one step closer to offering patients and physicians a highly effective, new, convenient and less invasive method of drug delivery,” said Doug Jeffery, M.D., Ph.D., Associate Professor, Wake Forest University Baptist Medical Center. “Previous Phase II studies have demonstrated positive results for laquinimod, and we hope that results from this pivotal Phase III trial will further reinforce these findings.”

Recently, Teva concluded a 36-week extension of the 36-week Phase IIb core trial, which demonstrated that laquinimod 0.6 mg met its primary endpoint. The data from this extension trial further confirmed and strengthened the results from the initial 36-week Phase IIb trial. The majority of the patients that have participated in the trial are now receiving treatment with laquinimod in a continued open-label extension trial.

“The initiation of Phase III clinical trial is a critical milestone for Teva in our commitment to the MS community,” said Moshe Manor, Group Vice President – Global Innovative Resources, of Teva Pharmaceutical Industries Ltd. ”We are excited about the development of Laquinimod, which together with Copaxone, will broaden our MS platform and position Teva as a leading company in the MS field.”

Additional new data, presented at the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on October 13, 2007 in Prague, demonstrated that laquinimod reduced inflammation, demyelination and axonal damage in an animal model experimental autoimmune encephalomyelitis (EAE), indicating that the compound may have both anti-inflammatory and neuroprotective properties.

Based on encouraging results from various animal models, laquinimod is now being investigated for other autoimmune diseases.

“We are very pleased to see how Teva has successfully advanced the laquinimod clinical trial program in order to bring a novel, first-in-class product to the market for the treatment of MS,” said Sven Andréasson, President and CEO of Active Biotech AB.

The efficacy, safety, and tolerability of laquinimod will also be studied in an additional Phase III pivotal trial in RRMS (BRAVO), which is expected to begin enrollment in the first quarter of 2008. This trial is a multinational, multi-center, randomized, parallel-group, placebo-controlled study which will compare the effects of laquinimod to those of placebo, and provide risk-benefit data comparing once-daily orally administered laquinimod to a product presently used for treatment of RRMS (an active comparator). This study plans to enroll approximately 1,200 participants who will be followed for 24 months.

 

About Allegro

Allegro is a multinational, multi-center, randomized, double-blind, parallel-group, placebo-controlled study, currently enrolling approximately 1,000 patients with RRMS. The globally conducted study will include centers in the United States as well as centers throughout Canada, Europe, and Israel.

 

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease-modifying treatment for RRMS. Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. A recent Phase IIb study in 306 patients was presented at the 2007 Annual Meeting of the American Academy of Neurology (AAN).

The data demonstrated that an oral 0.6 mg dose of laquinimod, administered daily, significantly reduced magnetic resonance imaging (MRI) disease activity by 40 percent versus placebo (p=0.0048) in RRMS patients, and was well tolerated. Looking into the median data of the primary end point laquinimod 0.6mg reduces disease activity (MRI) by 55% compared to placebo.

Laquinimod showed consistent and robust effect (statistical significant) on all secondary MRI end points. In addition, the study showed a favourable trend toward reducing annual relapse rates and the number of relapse-free patients compared with placebo. Treatment with both 0.3 and 0.6 mg doses were well tolerated with only some transient and dose-dependent increases in liver enzymes reported. To date 460 MS patients have received laquinimod in various clinical trials.

 

Source: Teva Pharmaceutical Industries Ltd.(07/11/07)

 

Teva and Active Biotech to Initiate Pivotal Phase III Trial Program of Oral Laquinimod for Relapsing Multiple Sclerosis

 

Teva Pharmaceutical Industries Ltd. and Active Biotech AB today announced that the companies are initiating a clinical Phase III program for laquinimod, a novel once-daily, orally administered immunomodulatory compound for the treatment of relapsing multiple sclerosis (RMS). The studies will now begin following the successful conclusion of a second phase II study and the outcome of discussions with the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMEA).

The companies are to commence two global Phase III trials of laquinimod during this year. The Phase III trials will take place in centers in the United States, Europe, and other locations worldwide, to further confirm the results of the Phase II trials.

“We are extremely excited about initiating the Phase III clinical program for oral laquinimod, as we believe laquinimod is a potential new and convenient treatment option for MS patients,” said Shlomo Yanai, President and CEO of Teva Pharmaceutical Industries Ltd. “The accelerated development of oral laquinimod is part of our commitment to MS patients to develop additional improved therapies that combine superior efficacy and excellent safety.”

“Laquinimod has the potential to be a novel, orally-administered disease modifying treatment for people suffering from multiple sclerosis,” said Sven Andréasson, President and CEO of Active Biotech. “Laquinimod would represent a milestone for patients as it would provide them with an efficacious and safe treatment, as well as a new drug delivery option that is suitable for long-term treatment.”

 

About Phase II Laquinimod Trials

Results from a 36-week, randomised, double-blind, placebo-controlled Phase IIb trial evaluating the effect of oral daily 0.3 and 0.6 mg doses of laquinimod on magnetic resonance imaging (MRI) -monitored disease activity in patients with RRMS were recently presented at the American Academy of Neurology (AAN) Annual Meeting in May, 2007. Data from the trial demonstrated that an oral 0.6 mg dose of laquinimod given daily significantly reduced MRI disease activity by 40 percent in RRMS patients and was well tolerated. In addition, there was a favorable trend towards reducing annual relapse rates, the number of relapse-free patients and time to first relapse compared with placebo. Treatment with both 0.3 and 0.6 mg doses of laquinimod were well tolerated with only some transient and dose-dependent increases in liver enzymes.

A previous 24-week Phase IIa trial conducted by Active Biotech demonstrated that oral 0.3 mg laquinimod given daily was well tolerated and reduced the formation of active lesions in RRMS.

 

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound that is being developed as a disease modifying treatment for multiple sclerosis (MS). Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries, Ltd. in June 2004. To date, 460 MS patients have received laquinimod in various clinical trials.

Source: Teva and Active Biotech (08/06/07)

 

Laquinimod cuts multiple sclerosis relapse

 

Teva Pharmaceutical Industries Ltd. and Active Biotech AB has announced that data from a 36-week, randomised, double blind, placebo-controlled phase IIb study demonstrated that an oral 0.6 mg dose of laquinimod given daily significantly reduced magnetic resonance imaging (MRI) disease activity by 38 per cent in RRMS patients and was well tolerated. In addition, there was a favourable trend towards reducing annual relapse rates, the number of relapse-free patients and time to first relapse compared with placebo.

Treatment with a 0.3 mg dose showed no statistical significant difference compared with placebo. “Current RRMS options are effective for the treatment of the disease, but an oral therapy such as laquinimod would represent a milestone for patients as it would provide them with a completely unique, non-invasive method of drug delivery,” said Giancarlo Comi, MD, director of department of neurology and institute of experimental neurology, Universita Vita-Salute, San Raffaele, Milan, Italy.

“Preliminary studies have already demonstrated the positive effect of laquinimod versus placebo, but these new data confirmed that a higher dose was even more effective and remained well tolerated.” The 36-week study evaluated the effect of oral daily 0.3 and 0.6 mg doses of laquinimod on MRI-monitored disease activity in patients with RRMS. The majority of the patients who participated in the study continued treatment with laquinimod in an ongoing, blinded 9 month extension study. This extension study is followed by an open label study where patients will receive 0.6 mg laquinimod for an additional 24 months.

“The results of this study, which once again demonstrate the efficacy and tolerability of once-daily oral laquinimod, are very exciting for the MS community both patients and researchers,” said Shlomo Yanai, president and CEO of Teva Pharmaceutical Industries Ltd. “Teva will soon initiate phase III studies to confirm oral laquinimod’s therapeutic benefits, and we expect to begin enrolment of the trial later this year.”

Source: Pharmabiz.com Copyright © Saffron Media Pvt. Ltd.(05/05/07)

 

Laquinimod Phase IIb Trial Confirms Efficacy and Favourable Safety Profile and Shows Significant Reduction in the Rate of Inflammatory Disease Activity

 

Teva Pharmaceutical Industries Ltd and Active Biotech AB today announced that a Phase IIb study designed to evaluate the safety and efficacy of laquinimod, a once-daily novel oral agent, in relapsing remitting multiple sclerosis (MS) patients, met its primary end-point.

Laquinimod treatment significantly reduced the rate of inflammatory disease activity, as measured by the cumulative number of Gadolinium enhancing lesions on brain MRI scans after 36 weeks of treatment. Laquinimod treatment also demonstrated a considerable reduction in the number of clinical relapses compared to placebo. This Phase IIb multi-center, randomized, double-blind, placebo-controlled study enrolled approximately 300 patients in 8 European countries and in Israel.

The evaluation of the safety and side-effect data confirmed the favourable safety profile that was seen in earlier phase II clinical trials. The majority of the patients who participated in the study are currently continuing treatment with laquinimod in an ongoing, blinded extension study.

“The study results with once daily oral laquinimod are very encouraging and further demonstrate our ongoing commitment to developing new classes of therapies for MS, including oral therapies, to treat the disease, as well as to improve the patients’ quality of life”, said Israel Makov, President and CEO of Teva Pharmaceutical Industries Ltd.

“As of today, nearly 400 patients have received laquinimod in various clinical trials over the last years. The data from the completed studies together with preclinical documentation, confirm laquinimod’s efficacy and favorable safety profile in MS patients,” said Sven Andreasson, President and CEO of Active Biotech AB.

The positive result of the clinical trial triggers a milestone payment to Active Biotech.

Further details about the study will be given at Teva’s Innovative R&D Day in New York City on September 26th, 2006. A complete presentation of the Phase IIb data will be given at upcoming relevant scientific meetings.

Teva is discussing laquinimod’s development plan with regulatory authorities in order to accelerate the clinical program into Phase III.

 

About Laquinimod

Laquinimod is a novel once-daily, orally administered immunomodulatory compound developed as a disease modifying treatment for multiple sclerosis (MS). Active Biotech developed laquinimod and licensed it to Teva Pharmaceutical Industries Ltd. in June 2004.

Source: Teva Pharmaceutical Industries Ltd

© Multiple Sclerosis Resource Centre

 

To Join this Trial Go To:

 

http://www.tevaclinicaltrials.com/

This will take you to the Allegro Website.  Allegro is conducting the clinical trial for Teva.

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