BG-12 In MS, Two Long-Acting Hemophilia Drugs Key To Scangos’ Revitalized Biogen Idec

An R&D overhaul trimmed 17 candidates from pipeline, but as several late-stage programs near potential approval, the biotech says it will resume focus on discovery and validation of new targets.

In the 18 months since George Scangos arrived from Exelixis Inc. to take the chief executive’s spot at Biogen Inc., the big biotech has overhauled its R&D apparatus, cutting two major therapeutic areas while tightening focus around another three areas.

As the company provided an R&D update during an analyst day presentation June 12, it remained clear, though, that while much has changed at Biogen, near-term future prospects for growth center on BG-12 in multiple sclerosis and a pair of long-acting coagulation factors in hemophilia.

Shortly after taking control, Scangos brought in former ZymoGenetics Inc. CEO Douglas Williams as executive VP, R&D (Also see "Energized Biogen Idec On Track For Two Filings In 2012" - Pink Sheet, 31 Jan, 2012.). At the investor meeting, Williams claimed “significant progress” in restructuring Biogen’s R&D and said that as several candidates near regulatory decisions in the U.S. and Europe, the biotech now will resume efforts in discovery and validation of new targets. “We have one of the most robust late-stage pipelines in the industry with the potential to launch multiple therapies in coming years in multiple sclerosis, hemophilia and amyotrophic lateral sclerosis (ALS),” he said.

In immunology, Biogen will focus on fibrosis, autoimmunity and tissue injury, Williams told the assemblage. But at the same time, having de-emphasized discovery work in recent years, he said the company needs to return to target identification and validation, with a focus on proprietary targets and first-in-class drug candidates that can differentiate Biogen’s pipeline from that of its competitors.

Two initiatives to begin this process are the Harvard Interactome Project, which will attempt to map the human proteasome and, in effect, diagram the thousands of protein-protein interactions that occur within cells, Williams explained. Biogen also has convened an ALS consortium with several academic researchers, who plan to sequence the entire genome and exomes of 600 ALS patients and families in which the disease has been prevalent. The effort’s goals are to identify new ALS genes that can be used for patient stratification and to find new pathways for validation as drug targets.

Near-Term Prospects In MS, Hemophilia, ALS

The company’s near-term prospects center on potential U.S. and EU approval of the oral BG-12 (dimethyl fumarate) for MS, where Biogen already has a strong presence through its marketing of the intravenous drug Tysabri (natalizumab) and the injectable Avonex (interferon beta-1a). In Europe, it also markets Fampyra (fampiridine) under a license from Acorda Therapeutics Inc.

BG-12, for relapsed, remitting MS, was accepted for review in May by both FDA and the European Medicines Agency. The FDA filing occurred in the first quarter and is subject to a 10-month standard review, so Biogen is anticipating a U.S. approval in early 2013. The filings are backed by data from a pair of global, placebo-controlled Phase III trials (DEFINE and CONFIRM), which showed significant reduction in MS disease activity, with favorable safety and tolerability, through activation of the Nrf-2 pathway.

The company’s plan is to use BG-12 to augment its market share in MS, rather than to cannibalize Avonex, or other standard, similar MS therapies, like Bayer AG’s Betaseron (interferon beta) and Teva Pharmaceutical Industries Ltd.’s market leading Copaxone (glatiramer acetate).

“We have a deep understanding of the multiple sclerosis market and believe that we have the right strategy and insights to grow not only our market share but the market overall with the potential launch of multiple new therapies,” said Scangos, referring to both BG-12 and an ongoing Phase III study that aims to add the latest-stage of MS, secondary progressive MS, to Tysabri’s label.

Despite the fact that Novartis AG’s Gilenya (fingolimod) already has reached market as an oral MS drug and Sanofi’s teriflunomide may be on track to beat BG-12 to market slightly, Biogen believes there remains significant unmet need for an oral MS therapy. The firm plans to deploy separate marketing teams for Tysabri, Avonex and BG-12, with a focus for BG-12 of siphoning market share from Merck and Teva. More sophisticated MS clinicians will use BG-12 over other options, the company contends.

In a same-day note, Robert W. Baird & Co. Inc. analyst Christopher Raymond maintained a bullish outlook for BG-12, predicting a successful launch in 2013, and blockbuster sales the following year. The analyst projects 2013 sales of $500 million, rising to $1.05 billion in 2014 and $1.54 billion in 2015. “For BG-12, management projects broad, early adoption, which we believe is already largely reflected in estimates,” Raymond wrote June 12, maintaining a “neutral” rating on Biogen shares. “Notably, all this feedback is consistent with recent MS survey feedback.”

Biogen also expects data in 2015 from the ASCEND trial, which is testing Tysabri’s ability to reduce cerebrospinal fluid concentrations of the chemokine CXCL13 in MS patients, a factor it believes is implicated in disease progression, said Alfred Sandrock, senior VP, development sciences, and chief medical officer. The Phase III, placebo-controlled study will exclude patients with relapsed, remitting and primary progressive MS, and will measure the advancement of disease-related disability based on a composite endpoint.

Beyond MS, Biogen is also studying the autoimmune disease ALS, also known as Lou Gehrig’s disease, which is currently treated with Sanofi’s Rilutek (riluzole). Biogen has dexpramipexole, a mitochondrial modulator, in Phase III with data expected during fourth-quarter 2012. In Phase II, the compound demonstrated a dose-dependent decrease of disease activity as measured by the revised ALS functional rating scale (ALSFRS-R). At 300 mg, the highest dose tested, the drug showed a 50% reduction compared with placebo, Sandrock said.

The Phase III EMPOWER trial uses inclusion and exclusion criteria virtually identical to those used in the Phase II program, he said, and is testing a 150 mg dose twice-daily for up to 18 months of treatment. Dexpramipexole has orphan drug status in the U.S. and Europe and fast-track status at the FDA. EMPOWER’s primary endpoint will be a composite endpoint called CAFS – combined assessment of function and survival, with secondary endpoints including time to death or respiratory insufficiency, respiratory decline and change in muscle strength.

Hemophilia Success Depends On Long-Acting Formulation

Hemophilia is a new therapeutic area for Biogen but the company thinks it can win market share away from existing coagulation factor products with longer-lasting factor VIII (for hemophilia B) and factor IV (for hemophilia A) products, both of which are in Phase III development. Data from the A-LONG and B-LONG trials are expected in the second half of 2012, said Glenn Pierce, senior VP, global medical affairs and hemophilia.

The rFIXFc product for hemophilia A has a three-fold prolonged half-life compared to competitor BeneFIX from Pfizer Inc., he said, while rFVIIIIFc for hemophilia B has a 1.5 to 1.7 prolonged half-life advantage over Baxter International Inc.’s Advate.

The A-LONG trial includes an arm testing a weekly dose of rFIXFc – previously it was not believed a safe, one-week dosage of Factor VIII could be developed, noted Deutsche Bank AG analyst Robyn Karnauskas in a June 12 note. “We highlight that the trial continues to treat patients on the weekly regimen, which could mean that patients are not experiencing excessive bleeding episodes,” she wrote.

Long-lasting coagulation factors offer a significant opportunity in hemophilia A and B, Tony Kingsley, executive VP, global commercial operations, explained during his presentation, because prophylaxis accounts for 75% of both factor VIII and factor IX use in the U.S. In market research, U.S. physicians identified longer-acting coagulation factors as the top unmet need in both types of the disease, he said.