Think back to the worst stomach flu you’ve ever had. Now imagine the horrible diarrhea you experienced during that 24- to 36-hour period was your daily normal—day in, day out— indefinitely. That might give you some idea why patients with carcinoid syndrome are so excited about the approval this year of first-in-class telotristat ethyl (Xermelo, Lexicon) for the treatment of carcinoid syndrome diarrhea.

Carcinoid tumors are neuroendocrine masses that often develop in the gastrointestinal tract, particularly in the stomach and intestines, rectum, liver and colon. These slow-growing cancers are rare, diagnosed in about 12,000 people in the United States every year. Because of their slow pace of growth, these tumors can go undetected for years, causing few symptoms—primarily intermittent abdominal pain—and even when they have spread to local lymph nodes, often are still amenable to surgical resection.

But a subset of patients with carcinoid tumors develop carcinoid syndrome, a condition caused when the tumors overproduce hormones (primarily serotonin), proteins and other chemical substances. (These are known as “functioning” tumors.) The hormone release triggers a host of symptoms, including flushing, shortness of breath and wheezing, rapid heart rate, and sudden drops in blood pressure. But perhaps the most debilitating manifestation is frequent and severe diarrhea. Approximately 75% of patients with carcinoid syndrome experience diarrhea, with as many as 30 episodes of loose stools daily (Gastroenterol Nurs 2002;25[3]:105-111; World J Surg 1996;20[2]:126-131).

Gary Rice, RPh, MS, MBA, CSP

“These patients often have to go on disability due to the number and severity of their diarrhea episodes,” said Gary Rice, RPh, MS, MBA, CSP, the executive vice president of operations for Diplomat, which is one of the specialty pharmacies in Lexicon’s limited distribution network for telotristat.

Somatostatin analog (SSA) medications, including octreotide (Sandostatin, Novartis) and lanreotide (Somatuline Depot, Ipsen), are used to treat carcinoid syndrome, but some patients still experience as many as a dozen diarrhea episodes daily while taking these treatments. “Many of them end up taking a long-acting SSA and then supplementing it with short-acting drugs for diarrhea, including over-the-counter drugs, or short-acting SSAs, which can be challenging to use,” Mr. Rice told Specialty Pharmacy Continuum.

Evidence from TELESTAR

Telotristat, which received FDA priority review, fast track designation and orphan drug designation, has a different mechanism of action than the SSAs, specifically targeting tryptophan hydroxylase, an enzyme responsible for excess serotonin production. In TELESTAR, a 12-week randomized, double-blind, placebo-controlled, multicenter trial involving 90 patients who were having between four and 12 daily bowel movements despite the use of SSA therapy, patients on telotristat experienced a significant reduction in bowel movement frequency, beginning as early as one to three weeks after initiating therapy and persisting for the length of the study. Specifically, according to a company release, 33% of patients taking telotristat had an average reduction of two bowel movements per day, compared with 4% of those randomly assigned to placebo add-on to their SSA regimen. (Trial results had not yet been published in the literature at press time.)

The telotristat approval “establishes a new treatment option for patients with carcinoid syndrome diarrhea that is inadequately controlled by SSA therapy,” said Matthew H. Kulke, MD, a TELESTAR primary investigator and the director of the Program in Neuroendocrine and Carcinoid Tumors at Dana-Farber Cancer Institute, in Boston, in a Lexicon statement. “Inhibition of tumoral serotonin production represents a novel approach for patients with this condition.”

Oral Rx a Benefit

When telotristat is used with an SSA analog, it “allows these patients—for the first time—to have an oral treatment that could [mitigate] the frequency and severity of their diarrhea, hopefully allowing them to reduce episodes so that they can be employed, have a social life,” among other benefits, Mr. Rice said.

The major side effect associated with telotristat has been constipation, which Mr. Rice noted has proven manageable in most patients with careful dose monitoring.

Smooth Access

In the first six months on the market, Diplomat reported that there have been few if any roadblocks to access for the drug, which is taken orally three times daily with food. The drug’s monthly wholesale acquisition cost is about $5,100, Mr. Rice said, noting that this is less than the monthly cost of SSAs. “So far, we have had no difficulties with insurance coverage and prior authorizations. As long as the patient is appropriately diagnosed and being followed by an oncologist, there have been no issues.”

Lexicon has established a patient registry for telotristat. In addition to tracking side effects such as constipation and the success of weaning patients off SSA, the registry also will track other possible long-term benefits of the agent. Patients with carcinoid syndrome experience frequent cardiovascular side effects, which can ultimately necessitate stents or bypass procedures, and the registry will help assess whether there is any positive long-term effect on these cardiovascular issues, although it will likely take several years before such an effect would become evident.

—Gina Shaw

The sources reported no relevant financial relationships.