Pharm Exec's 2013 Pipeline Report - Pharmaceutical Executive


Pharm Exec's 2013 Pipeline Report

Pharmaceutical Executive

Multiple Sclerosis: We've Got Your Number

In the mid-1990s, the first disease-modifying drugs entered the market for MS: interferon treatments like Betaseron and Avonex on the one hand, and Copaxone on the other. For a while, interferon and Copaxone were the only two options, both of which were injected, and reduced relapse rates by around 30 percent. Then Tysabri arrived in 2006, followed by Gilenya in 2010. Both of those drugs have safety issues, but they nearly doubled the efficacy rates of the previous generation of drugs.

The next big thing in MS, according to everyone who has an opinion on the matter, is Biogen Idec's BG-12, one of the most hyped products in any category. On track to receive approval this year, BG-12 had a PDUFA date of December 28 up until mid-October, when FDA announced that it needed more time to evaluate the drug's application. The agency didn't request additional studies, and Biogen CEO George Scangos, on a 3Q earnings call a few days after the announcement, didn't seem overly concerned. "While this three-month delay is disappointing, our view of the potential of BG-12 to benefit patients with MS has not changed," said Scangos on the call. Pivotal data published recently in the New England Journal of Medicine "form the foundation of our regulatory filings, and support BG-12's potential as a new oral option for MS treatment," he said.

"BG-12"—or dimethyl fumarate—"has been used for a long time in psoriasis in Europe, so there's more comfort around that drug than most," notes inThought's Ben Weintraub. "But I still think it will turn out that in some cases you need stronger medicines, and in some cases you need weaker ones, so that plays into Sanofi's approach. They have a strong one with Lemtrada, and a weaker, safer one with [recently approved] Aubagio." In a Phase III trial, patients whose prior MS treatment was inadequate at preventing relapses experienced a slowing or reversal of their disability with Lemtrada (alemtuzumab), according to company statements. Lemtrada has filed in Europe and the United States, and could gain approval during the second quarter of 2013.

Genzyme and Sanofi are dedicated to MS, but many believe Biogen Idec will dominate the category, at least in the near term. "If you look at all that has happened over the course of the last three of four years in MS R&D, the inescapable conclusion is that Biogen Idec is the 800-pound gorilla in the space," says Selvaraju. "They have a symptomatic therapy that they market outside the United States, they have two monoclonal antibodies, both of which have performed well in mid-to-late stage studies"—daclizumab and ocrelizumab—"they have a best-in-class oral therapy in BG-12, and they have one of the older generation injectable drugs, Avonex, in addition to Tysabri."

Note: In 2010, Genentech and Biogen Idec amended their antibodies deal and agreed that Genentech would take on full responsibility for the development of ocrelizumab. As stated in the agreement, Genentech assumed development and commercialization costs supporting ocrelizumab, and Biogen, if the drug is approved, is entitled to tiered, double-digit royalties on any US sales.

In May, Teva's CEO Shlomo Yanai announced that he would step down as the company's CEO, due in part to investor concern over the upcoming patent expiry of Copaxone in 2015, one of the company's few branded drugs. Copaxone earned over $3.5 billion in 2011, and represents a fifth of the company's total sales. Jeremy Levin, a former BMS executive and Teva's new CEO, said in a recent interview that any generic form of Copaxone would require extensive clinical trials to prove equivalency, according to a Financial Times report. In August, Teva received approval to conduct a Phase III trial in the United States on laquinimod—a once-daily immunomodulatory compound—for relapsing-remitting MS, under a Special Protocol Assessment. The trial, called CONCERTO, will evaluate two doses of laquinimod in approximately 1,800 patients for up to two years. The primary outcome measure will be confirmed disability progression, as measured by the Expanded Disability Status Scale.

Laquinimod "is the safest oral therapy" in development, per Selvaraju, but it failed to meet its primary endpoint of reducing annualized relapse rates versus placebo during a pivotal Phase III trial in 2011. Still, Selvaraju says laquinimod "may have an impact in terms of preserving brain tissue, or enhancing endogenous regeneration," in which case the drug may yet prove saleable.


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