Teva Pharmaceutical Industries Ltd.'s investigational immunomodulator laquinimod appears to be holding up to investors' modest expectations following the release of initial Phase III data, as a relatively safe, moderately efficacious once-daily oral treatment for relapsing remitting multiple sclerosis.

The company released the results of the two-year Phase III ALLEGRO study, comparing laquinimod to placebo, after market close April 11 - four days ahead of a scheduled late-breaking presentation at the American Academy of Neurology annual meeting.

Although the efficacy results underwhelmed investors, ALLEGRO did meet its primary endpoint with a statistically significant reduction in annualized relapse rate (ARR), and it met several secondary endpoints as well.

Importantly, the safety profile of laquinimod held up. Though some increases in liver enzymes were seen, no immunosuppressive impacts were noted and no deaths were reported. A clean safety profile is critical for laquinimod if Teva is to establish the drug as a more convenient alternative to existing first-line injectable medications and as a therapy of choice over other oral agents with more impressive efficacy data.

The market for multiple sclerosis drugs is growing increasingly fierce, and new entrants must come to the market with strong efficacy and safety profiles in order to be commercially viable. The first-ever oral agent for multiple sclerosis, Novartis AG's Gilenya (fingolimod), already launched in October (Also see "Novartis' Gilenya: Efficacy, Patient Assistance Lie At Heart Of Marketing Push" - Pink Sheet, 11 October, 2010.). Biogen Idec Inc. also has an oral drug, BG-12 (dimethyl fumarate), in Phase III development.

Just ahead of Teva's announcement, Biogen revealed some positive news on BG-12. In a Phase III study, DEFINE, BG-12 met its primary endpoint of a significant reduction in the number of patients who relapsed at two years and met its secondary endpoint of a significant reduction in annualized relapse rate in patients treated with BG-12 twice daily and three times daily. The company provided no additional details on the study results, but the dosing news is considered a positive turn for Biogen since twice-daily dosing could improve the drug's commercial odds.

In addition to Gilenya and BG-12, Genzyme Corp., in the midst of its acquisition by Sanofi-Aventis SA, is studying Lemtrada (alemtuzumab) in Phase III studies for multiple sclerosis. While not an oral drug, Lemtrada is a once-yearly infusion, and it is expected to have strong efficacy, though its safety profile remains a concern (Also see "Where Does Genzyme See Alemtuzumab For MS? After Gilenya, Before Tysabri" - Pink Sheet, 21 December, 2010.).

Investors Reserve Applause For BRAVO Results

The ALLEGRO results left investors wanting, and data from a second Phase III study, BRAVO, comparing laquinimod to Biogen Idec's market-leading interferon Avonex (interferon beta-1a) are expected in the third quarter. The head-to-head data could provide more clarity on laquinimod's potential market position, and most industry observers are awaiting the additional data before drawing conclusions.

Teva management said the ALLEGRO data position laquinimod as a first-line treatment option. "Clearly, these impressive efficacy endpoints, combined with uncompromised patient safety, position laquinimod as a first-line treatment in a broad patient population, as prescribers and patients will continue to rely primarily on treatments that can be used safely," President and CEO-Americas Bill Marth said during a same-day conference call.

Analysts were less enthusiastic, but still see promise for laquinimod. "We think laquinimod's overall clinical profile is still compelling and that it could be a very successful MS drug over time," Deutsche Bank analyst David Steinberg said in a next-day note.

Jeffries analyst Corey Davis commented April 12, "We are not ready to declare laquinimod having billion dollar potential, but at this point, it seems like 'hundreds of millions' should be achievable. Although this would not be a replacement for Copaxone (glatiramer), it certainly helps."

Teva's MS drug Copaxone generated sales of $3.32 billion in 2010, but the drug is facing multiple patent challenges from Momenta Pharmaceuticals Inc. and Novartis AG's Sandoz unit and from Mylan Inc. The final patent protection for the drug expires in 2014, but Teva has argued that generic versions should not be approved without clinical trials because of the drug's complexity (Also see "The Lovenox Benchmark: Copaxone "Far More Complex," Teva Argues In Anti-Generic Petition" - Pink Sheet, 3 January, 2011.).

A Closer Look At Laquinimod Efficacy Data

In the ALLEGRO study, laquinimod showed a statistically significant 23% reduction in ARR, the primary endpoint, and a 36% reduction in the risk of confirmed disability progression, as measured by the Expanded Disability Status Scale.

While it is difficult to compare across clinical trials, the relapse rate appears slightly better than that seen in clinical trials for Avonex (18%) but inferior to that seen with most other agents including Copaxone (29%), Biogen/Elan's Tysabri (67%) and Novartis' Gilenya (58%), according to a comparison by Credit Suisse analyst Ravi Mehrotra. Tysabri (natalizumab) and Gilenya have demonstrated superior efficacy but are associated with serious side effects. On reduction in disability progression, laquinimod stacks up on par with most of the competition: Avonex (37%), Tysabri (41%) and Gilenya (37% to 40%), Mehrotra's analysis shows.

ALLEGRO was a two-year, multi-national, multi-centered trial that enrolled 1,106 multiple sclerosis patients, randomized to receive an oral dose of 0.6 mg laquinimod once-daily or placebo.

-Jessica Merrill (j.merrill@elsevier.com

No Homerun, But A Base Hit For Teva's Laquinimod

More from Archive

More from Pink Sheet