Teva Pharmaceutical Industries Ltd. and Swedish partner Active Biotech AB released initial results from their first pivotal Phase III study of the oral multiple sclerosis therapy, laquinimod, on Dec. 9, showing that it reduced relapse rates relative to placebo.

Although a competing oral MS drug, Novartis AG's Gilenya (fingolimod), has beaten it to the market, laquinimod's relatively clean safety profile is expected to be one of its key advantages. Fingolimod was launched in the U.S. in October with a stringent risk reduction strategy ("Also see "Novartis Gilenya Approved With Advisory Panel-Enhanced REMS" - Pink Sheet, 22 September, 2010.).

Another potential oral MS product, Merck KGaA's cladribine, has been approved for marketing in Australia and Russia, but its U.S. priority review period has been extended to Feb. 28, 2011, and EU regulators turned it down ("Also see "EU Regulators Reject Merck KGaA's Oral MS Drug Cladribine" - Pink Sheet, 24 September, 2010.).

If Teva can win approval for laquinimod, it will add to the Israeli company's strong presence in the MS sector, where its injectable product, Copaxone (glatiramer acetate), is the market leader, with a 30% global share of disease-modifying drugs. Worldwide sales of Copaxone totaled $808 million in the third quarter. However, generic versions of Copaxone are waiting in the wings, even though Teva believes it has patent protection on the product until at least 2015 ("Also see "Follow-on Biologic's Day Will Come - Post 2015, Teva Says" - Pink Sheet, 12 January, 2010.).

Teva has worked for years to find an acceptable oral MS successor to Copaxone, only to see potential candidates falter, but laquinimod appears to be the most promising.

In Teva's Phase III ALLEGRO study, laquinimod 0.6 mg/day met the trial's primary endpoint of significantly reducing the annualized relapse rate, when compared with placebo, in patients with relapsing-remitting MS. The study also found a statistically significant reduction in disability progression, as measured by the Expanded Disability Severity Scale (EDSS).

Laquinimod was reported to be safe and well tolerated, with the frequency of adverse events in the active treatment group being comparable to those in the placebo group. No deaths were reported in laquinimod-treated patients, and the overall incidence of infections, which can become an issue for immunosuppressive products, was similar between the two arms of the trial. ALLEGRO involved more than 1,000 MS patients from 24 countries.

These top-line results, which came slightly earlier than the expected, cheered analysts at the Swiss investment bank UBS, who commented that they were a "giant step in the right direction" for Teva's MS franchise, bearing in mind the moderate efficacy previously seen with laquinimod in Phase II.

But they cautioned that further details of the study's findings need to be seen. Teva said that it would release those at a major scientific conference during the first half of 2011.

The U.S. and EU submissions for laquinimod will wait for the release of results of the second Phase III study, BRAVO, expected in the third quarter of 2011. BRAVO is a two-year randomized study comparing the safety and efficacy of laquinimod 0.6 mg/day with placebo and interferon beta-1a, a standard MS therapy.

The principal investigator of the ALLEGRO study, Giancarlo Comi of the Institute of Experimental Neurology at the University Vite Salute, San Raffaele, Italy, said that the unique mechanism of action of laquinimod may account for its beneficial effects. Previous laboratory research suggests that laquinimod affects inflammatory processes in the central nervous system, as well as increasing levels of brain-derived neurotrophic factor.

Two Types Of MS Product?

Therapeutic products for MS may in the future be divided in two types, highly potent compounds like Biogen Idec Inc.' s Tysabri (natalizumab) and Gilenya, and less potent but better tolerated compounds like beta-interferon and laquinimod, commented partner Active Biotech.

In February, Teva and Active Biotech amended their collaboration agreement, extending Teva's marketing and distribution rights to become worldwide. They previously excluded the Nordic and Baltic regions ("Also see "Teva Targets $113 Billion In Branded Sales With Dozens Of Pending Applications" - Pink Sheet, 16 February, 2010.).

Laquinimod is also in Phase II development for Crohn's disease and lupus, and is being studied in other autoimmune diseases.

- John Davis (j.davis@elsevier.com )

Teva's Laquinimod Meets Primary Endpoint In First Phase III Study

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