Injectable Therapy Receives Expanded Approval for Ulcerative Colitis

The FDA expanded the approval of Simponi^®(golimumab) in May 2013 to treat adults with moderately to severely active ulcerative colitis. The drug, an injectable anti-tumor necrosis factor-alpha treatment from Janssen Biotech, Inc, is also approved to treat patients with moderately to severely active rheumatoid arthritis, active psoriatic arthritis, and active ankylosing spondylitis. Last year, golimumab generated $607 million in sales and could reach $1.2 billion by 2016, according to a Bloomberg News article.

“The FDA approval of [golimumab] brings an important, new subcutaneous therapeutic option to adults living with moderate-to-severe ulcerative colitis, a disease where treatment options have been limited,” William Sandborn, MD, the lead author of the golimumab trials and a professor and chief of the division of gastroenterology at the University of California, San Diego’s School of Medicine, said in a news release. “[Golimumab] has demonstrated significant benefits in the treatment of ulcerative colitis, a chronic inflammatory bowel disease, and represents a meaningful addition to the treatment armamentaria for gastroenterologists.”

For ulcerative colitis, patients are advised to have an initial 200-mg subcutaneous injection, followed by a 100-mg injection 2 weeks later, and a 100-mg injection every 4 weeks thereafter. For rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, the drug is administered via subcutaneous injection at a dose of 50 mg once per month.

Ulcerative colitis, a chronic disease affecting approximately 620,000 people in the United States, is one of 2 main types of chronic inflammatory bowel disease. The disease causes inflammation and ulcers in the lining of the large intestine and can lead to abdominal discomfort, gastrointestinal bleeding, bloody stools, and severe diarrhea. Although the average age of diagnosis is in the mid-30s, people of all ages can have ulcerative colitis. There is no cure for the disease, and approximately 30% of people with ulcerative colitis will require surgery at some point.

The approval of golimumab to treat ulcerative colitis was based on results of two phase 3, multicenter, randomized, double-blind, placebo-controlled clinical trials that were part of the Program of Ulcerative Colitis Research Studies Utilizing an Investigational Treatment (PURSUIT). The studies included patients who had previously failed or could not tolerate other therapies, including 6-mercaptopurine, azathioprine, corticosteroids, and/or 5-aminosalicylate.

Janssen reported interim results of the studies during Digestive Disease Week in May 2012 and at the annual meeting of the American College of Gastroenterology in October 2012. The company submitted an application for approval to the FDA in July 2012. The drug was first approved as a once-monthly, 50-mg subcutaneous injection for rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis in April 2009.

Patients in the PURSUIT studies were naïve to treatment with tumor necrosis factor inhibitors and had a baseline Mayo score between 6 and 12 on a 12-point scale and an endoscopic subscore of ³2, according to a Janssen news release. The Mayo score, a colonoscopy-based measure of disease activity, assesses improvement in symptoms based on rectal bleeding, endoscopic findings, stool frequency, and physician assessment.

The first trial enrolled 513 patients who were randomly assigned in a 1:1 ratio to receive golimumab or placebo. After 6 weeks of treatment, 52% of patients in the golimumab group had a clinical response compared with 30% of patients in the placebo group (P<.0001), and 19% of patients in the golimumab group had clinical remission compared with 6% of patients in the placebo group (P<.0001). In addition, 43% of patients in the golimumab group showed an improvement of endoscopic appearance of the mucosa at 6 weeks compared with 29% of patients in the placebo group (P=.0005).

The authors defined clinical response as a decrease from baseline in the Mayo score of ≥30% and ≥3 points as well as a decrease in the rectal bleeding subscore of ≥1 or a rectal bleeding subscore of 0 or 1. In addition, they considered clinical remission as a Mayo score ≤2 points and no individual subscore >1. Patients had an improvement in endoscopic appearance of the mucosa if they had a Mayo endoscopy subscore of 0 (normal or inactive disease) or 1 (erythema, decreased vascular pattern, mild friability).

Patients who had a prohibited change in concomitant ulcerative medication, an ostomy or colectomy, discontinued the drug because of a lack of therapeutic effect, or had a dose adjustment were considered not to be in clinical response, clinical remission or have an improvement in endoscopic appearance of the mucosa.

In the other study, the authors randomly assigned 310 patients in a 1:1 ratio to receive golimumab or placebo. Through week 54 of treatment, 51% of patients in the golimumab group had a clinical response compared with 31% of patients in the placebo group (P<.0001), while 29% of patients in the golimumab group had clinical remission at week 30 and week 54 compared with 15% of patients in the placebo group (P<.0001).

In both trials, the common side effects of patients treated with golimumab included upper respiratory infection and redness at the injection site.

The product’s Prescribing Information notes that patients who take golimumab are at an increased risk for developing serious infections caused by bacteria, fungi, or viruses that could lead to hospitalizations or death. The infections, including tuberculosis and histoplasmosis, are most often found in patients taking concomitant immunosuppressants such as methotrexate or corticosteroids.

Providers are advised to test patients for tuberculosis before prescribing golimumab and to monitor patients for tuberculosis throughout the treatment period. Patients should inform providers if they have a history of infection, diabetes, HIV, or a weak immune system. They should also tell them if they have conditions such as fever, sweat, or chills, muscle aches, cough, shortness of breath, blood in phlegm, weight loss, painful skin or sores on the body, diarrhea, or stomach pain.

Simponi Facts

•    Simponi was approved by the FDA on May 15, 2013, to treat moderately to severely active ulcerative colitis in adults dependent on corticosteroids or who had an inadequate response to or failed treatment with oral aminosalicylates, oral corticosteroids, azathioprine, or 6-mercaptopurine

•    Simponi is marketed by Janssen Biotech, Inc

Additional Resource

Prescribing Information for Simponi: https://www.simponi.com/shared/product/simponi/prescribing-information.pdf