Alongside the big-market patients that benefit from Amgen Inc.'s Enbrel, there are smaller inroads to patient populations that can be traveled to expand its reach.
Amgen, of Thousand Oaks, Calif., said Wednesday it filed a supplemental biologics license application for ankylosing spondylitis.
It is a smaller indication than Enbrel's other uses. The drug is approved for reducing the signs and symptoms and inhibiting the progression of structural damage in patients with moderately to severely active rheumatoid arthritis, for reducing the signs and symptoms of moderately to severely active polyarticular-course juvenile rheumatoid arthritis in those who have had an inadequate response to disease-modifying medicines, and for reducing the signs and symptoms of active arthritis in patients with psoriatic arthritis. Those three indications drive its sales, which for 2003 are anticipated to be between $1.2 billion and $1.4 billion.
The company is scheduled to release fourth-quarter and year-end earnings today after the markets close.
An approval for ankylosing spondylitis would mark Enbrel's fourth inflammatory indication, but Amgen also is developing the product for psoriasis. It said Friday the first of two Phase III trials in that indication hit primary and secondary endpoints. (See BioWorld Today, Jan. 21, 2003.)
Ankylosing spondylitis is a chronic inflammatory disease that mainly affects a patient's spine. It tends to begin in the lower back but might progress over time to the upper spine and spread to the chest and neck. The disease can result in partial or complete fusion of the spine, bringing about a loss of motion or deformity. It has been known to affect other joints besides those in the back, including the hips, shoulders and knees.
"It's an inflammatory disease, but we don't know the cause of it," said John Davis, assistant professor of medicine at the University of California at San Francisco. "But there is a genetic component to it - those that have [the marker] HLA B27 have a 10 percent chance of getting it in their lifetime. And if you have a first-degree relative that has AS and you have the marker, then you chances increase to 20 percent to 30 percent."
The supplemental BLA is based on three clinical trials involving 401 patients. The placebo-controlled Phase III study involved 277 patients with active ankylosing spondylitis, about half of whom were given Enbrel, and had a primary endpoint of a percentage of patients achieving the Assessment in Ankylosing Spondylitis Response Criteria, which measures back pain, inflammation and physical function. Some patients in the trial experienced relief from symptoms as early as two weeks, and overall, nearly 60 percent of patients met the primary endpoint after six months of treatment, compared to 23 percent for those receiving placebo, the company said.
Amgen spokeswoman Rebecca Hamm said the market in the U.S. annually is from 50,000 to 100,000 patients. Davis said the disease has a prevalence of 350,000 in the U.S., but globally it varies from area to area.
"Worldwide, it depends on the population because the marker travels in certain ethnic populations," David told BioWorld Today. "So, it's higher in places like Scandinavia but lower in Japan and Africa."
Amgen acquired Enbrel, a fully human antitumor necrosis factor receptor, through its purchase of Immunex Inc., of Seattle, completed in July. The deal was originally valued at $16 billion in December 2001, but sagging U.S. markets devalued the deal to its $10.3 billion closing value. (See BioWorld Today, Dec. 18, 2001, and July 17, 2002.)
Immunex had been investigating Enbrel in Wegener's granulomatosis, a disease characterized by necrotizing granulomas and ulceration of the upper respiratory tract. Whether that indication will be pursued is not yet known, Hamm told BioWorld Today.
"We're still looking at that," she said. "We are in the process of taking a look at some of the trials that were conducted before the acquisition of Immunex."
There are no treatments approved by the FDA for ankylosing spondylitis other than nonsteroidal anti-inflammatory agents. That route, however, addresses only the symptoms, Davis said, and does not affect the spine. But if all goes well, AS patients might have their first therapy.
"[The filing] offers great hope for patients to have a drug that affects the spinal system and can possible slow the progression of the disease," he said.
Amgen's stock (NASDAQ:AMGN) rose $1.63 Wednesday to close at $52.50.