Biotech Values

[DewDiligence]

The FDA has again overruled an advisory panel—the
drug is Roche’s Actemra for RA. Although the advisory
panel voted 10-1 in favor of immediate approval
(#msg-31066359), the FDA wants a risk-mitigation plan
and more animal data, delaying a possible approval by
at least a year. Actemra has been approved in the EU,
Japan, and Switzerland.

http://finance.yahoo.com/news/Roche-and-FDA-Agree-on-prnews-13741428.html

›Roche and FDA Agree on Pathway Towards U.S. Approval of ACTEMRA (tocilizumab)

Thursday December 4, 2008, 1:30 am EST

NUTLEY, N.J., Dec. 4 /PRNewswire/ -- Roche today announced that the U.S. Food and Drug Administration (FDA) has provided further guidance on the requirements for the Biologics License Application (BLA) for ACTEMRA® (tocilizumab), the first interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody studied for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA).

As a result of the FDA's evolving Risk Evaluation and Mitigation Strategy (REMS) requirements for medications, the Agency has clarified that a REMS plan is required to help ensure that health care professionals prescribe and administer ACTEMRA correctly, and that patients understand the potential benefits and risks associated with this medication. Additionally, based on the evolving requirements for approval of new biologics, the FDA has asked Roche for non-clinical animal model data, beyond what was included in the ACTEMRA BLA. Roche is performing the requested pre-clinical studies to confirm the published literature showing that ACTEMRA does not affect peri- and post-natal development, and fertility. The FDA has not requested additional clinical studies prior to approval.

The FDA Office of Compliance has also completed its evaluation of the manufacturing facility in Japan, and has indicated that it is acceptable to manufacture ACTEMRA.

In September, Roche received a complete response letter from the FDA for the ACTEMRA BLA. Since then, Roche has been engaged in productive discussions with the FDA and recently met with Agency representatives for clarification on the outstanding components related to the ACTEMRA BLA.

"Roche will continue to work diligently to fulfill the FDA's requirements, and we anticipate submitting the complete response for ACTEMRA to the Agency in the third quarter of 2009," said George Abercrombie, CEO and president of Roche. "Roche remains confident in the future of ACTEMRA and is committed to making this important new therapy available to patients with RA."

Roche submitted the BLA for ACTEMRA to the FDA on November 18, 2007. The BLA for ACTEMRA is based on the results of an extensive multi-national clinical development program, which included more than 4,000 patients in 41 countries, including the U.S. These studies demonstrated that treatment with ACTEMRA - alone or combination with methotrexate or other DMARDs (disease modifying anti-rheumatic drugs) - significantly reduced RA signs and symptoms, regardless of previous therapy or disease severity, compared with DMARDs alone. On July 29, 2008, the Arthritis Advisory Committee of the FDA voted 10-1 to recommend approval of ACTEMRA.

On December 3, 2008, the Swiss authorities approved RoActemra (tocilizumab, known as ACTEMRA outside the EU) for the treatment of moderately severe to severe, active rheumatoid arthritis in adult patients who did not respond adequately to treatment with DMARDs or tumor necrosis factor (TNF) inhibitors. RoActemra can be administered as a monotherapy or in combination with methotrexate and/or other conventional DMARDs. There are no significant post-approval commitments required.

On November 21, 2008, Roche announced that the European Committee on Human Medicinal Products (CHMP) provided a positive recommendation for RoActemra. This recommendation is for use of RoActemra in combination with methotrexate for the treatment of adult patients with moderate to severe RA who have either responded inadequately to, or who were intolerant to, previous therapy with one or more DMARDs or TNF antagonists. In these patients, RoActemra can be given as monotherapy in cases of intolerance to methotrexate or where continued treatment with methotrexate is inappropriate.

About ACTEMRA® (tocilizumab)

ACTEMRA is the first humanized interleukin-6 (IL-6) receptor-inhibiting monoclonal antibody being studied for the treatment of RA. Studies demonstrate that reducing the activity of IL-6, one of several key cytokines involved in the inflammatory process, relieves both inflammation of the joints and certain systemic effects of RA. The extensive clinical development program conducted by Roche includes five Phase III clinical studies and has enrolled more than 4,000 patients in 41 countries, including the United States. Four Phase III studies are completed and have reported meeting their primary endpoints. A fifth Phase III study, the LITHE study evaluating ACTEMRA in RA is an ongoing two-year study, which is expected to report complete data evaluating the effects of ACTEMRA on the inhibition of structural joint damage in 2009. ACTEMRA is currently under review in the United States and Europe.

ACTEMRA is part of a co-development agreement between Roche and Chugai Pharmaceutical Co. In June 2005, ACTEMRA was launched by Chugai in Japan as a therapy for Castleman's disease; in April 2008, additional indications for rheumatoid arthritis, juvenile idiopathic arthritis and systemic-onset juvenile idiopathic arthritis were also approved in Japan.

The serious adverse reactions reported in ACTEMRA clinical studies include serious infections, gastrointestinal perforations and hypersensitivity reactions including anaphylaxis. The most common adverse reactions reported in clinical studies were upper respiratory tract infection, nasopharyngitis, headache, hypertension and increased ALT. Increases in liver enzymes (ALT and AST) were seen in patients; these increases were generally mild and reversible, with no evidence of hepatic injuries. Laboratory changes, including increases in lipids (total cholesterol, LDL, HDL, triglycerides) and decreases in neutrophils and platelets, were seen in patients without association with clinical outcomes. Treatments that suppress the immune system, such as ACTEMRA, may cause an increase in the risk of malignancies.

About IL-6

IL-6 is a common protein found in all joints in the body and is a natural substance that can raise inflammation. Everyone has IL-6 in their body, but people with RA may have too much.

When approved, ACTEMRA will be the first and only medication to specifically target IL-6 in patients with RA.‹