FDA Approves Actemra for Giant Cell Arteritis - Drug Discovery and Development

Genentech’s tocilizumab (Actemra) subcutaneous injection was approved by the U.S. Food and Drug Administration (FDA) on Monday for the treatment of Giant Cell Arteritis (GCA). This is the sixth FDA approval for Actemra since it was launched in 2010—and the first drug approved to specifically treat patients with GCA.

GCA is a chronic and severe autoimmune condition that is a form of vasculitis, a group of disorders that results in inflammation of blood vessels. In GCA, also called temporal arteritis, the inflammation is in the arteries located near the temples. Symptoms include headaches, scalp tenderness, jaw pain and vision problems. If left untreated, it can cause stroke or blindness.

Corticosteroids are prescribed to control inflammation, relieve symptoms and help prevent vision loss. However, the high dose of corticosteroids prescribed carries serious side effects.

The expanded use of tocilizumab, a humanized interleukin-6 (IL-6) receptor antagonist, is approved for use in combination with steroids. This leads to a substantial reduction in the cumulative corticosteroid dose.

“Today’s FDA decision means people living with giant cell arteritis will, for the first time, have an FDA-approved treatment option for this debilitating disease,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development in a company statement yesterday. “With no new treatments in more than 50 years, this approval could be transformational for people with GCA and for their physicians.”

Efficacy and safety

The approval is based on the positive outcome of the Phase III GiACTA study evaluating tocilizumab in 251 patients with GCA from 76 sites in 14 countries.

The double-blind, placebo-controlled study investigated the efficacy and safety of tocilizumab as a novel treatment for GCA over the course of one year.

For the study, patients were randomized 1:1:2:1 to four groups:

A: short-course prednisone (26-week prednisone taper + weekly subcutaneous [SC] placebo)

B: long-course prednisone (52-week prednisone taper + weekly SC placebo)

C: weekly SC tocilzumab 162 mg + 26-week prednisone taper

D: every other week SC tocilizumab 162 mg + 26-week prednisone taper

Results showed 56 percent of patients in the weekly tocilizumab group and 53.1 percent in the bi-weekly tocilizumab group achieved sustained remission at 12 months compared to only 14 percent in the short-course prednisone group.

Sustained remission, defined as the absence of symptoms of giant cell arteritis, normalization of inflammatory laboratory tests, and tapering the use of prednisone (a steroid drug), was the primary efficacy endpoint.

The FDA granted this application a Breakthrough Therapy designation and a Priority Review.

“We expedited the development and review of this application because this drug fulfills a critical need for patients with this serious disease who had limited treatment options,” said Badrul Chowdhury, M.D., Ph.D., director of the Division of Pulmonary, Allergy, and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research in a FDA statement.

Subcutaneous Actemra was previously approved for the treatment of moderate to severely active rheumatoid arthritis. Intravenous Actemra was also previously approved for the treatment of moderate to severely active rheumatoid arthritis, systemic juvenile idiopathic arthritis and polyarticular juvenile idiopathic arthritis. Intravenous administration is not approved for giant cell arteritis.