A NEW DRUG FOR ITP

ASH 2008: Eltrombopag Offers "Important New Option" in ITP

December 10, 2008 (San Francisco, California) — Patients with chronic idiopathic thrombocytopenia purpura (ITP) now have another treatment option, which works in some patients when all other therapy has failed.

Results presented here at the American Society of Hematology (ASH) 50th Annual Meeting and Exposition show that eltrombopag (Promacta, GlaxoSmithKline) produced a response in 77% of patients who were refractory to all other treatments, and a response in 84% of patients who were heavily pretreated but not refractory. Patients had previously been treated with corticosteroids, immunoglobulin, anti-D, and rituximab (MabThera, Roche).

The responses were similar in patients who had received a splenectomy and those who had not, reported lead investigator Mansoor Saleh, MD, from Georgia Cancer Specialists, in Atlanta. These data come from the EXTEND study, an open-label extension study that followed up patients for 40 weeks after they had taken part in 6-week placebo-controlled studies.

Also presented at the meeting were data from the pivotal phase 3 study known as RAISE (Randomized Placebo-Controlled ITP Study With Eltrombopag), which were part of the package that secured approval from the US Food and Drug Administration for the drug on November 20.

Eltrombopag offers "an important new option in treating ITP," commented J. Evans Sadler, MD, PhD, from the Division of Hematology at Washington University, in St. Louis, Missouri. It can reduce the need for steroids and might save some patients from undergoing a splenectomy, he commented to Medscape Oncology.

"It's an enormous boon to the management of these patients," commented Sherrill Slichter, MD, from the Puget Sound Blood Center, in Seattle, Washington. "It is of enormous benefit to some patients," she said, "although you have to continue to give the drug, so it is a treatment, not a cure."

First Oral Drug, Injectable Already Available

Eltrombopag is the first oral nonpeptide thrombopoietin-receptor agonist that stimulates the bone marrow into producing megakaryocytes, the precursors to platelets. Another drug with this novel mechanism of action, romiplostim (Nplate, Amgen), was approved for ITP in August 2008, but that drug is a peptide and is administered subcutaneously once weekly.

The fact that these drugs work in ITP confirms the fact that there is an underlying problem with the production of platelets, at least in some patients, commented Dr. Slichter. "This represents a huge change in the thinking of this disorder," she said, because it was thought for years that the main pathology involved an increased destruction of platelets. In fact, her group "got a lot of grief" in the 1980s when they tried to publish data suggesting that a decreased production of platelets was involved, she told Medscape Oncology, so "we are ecstatic now that this mechanism is accepted."

Gregory Chang, MD, from the Chinese University of Hong Kong, who presented the RAISE data at the meeting, said that as many as 50% of patients with chronic ITP could have a problem with the production of platelets.

Pivotal data for romiplostim were presented at last year's ASH meeting. This year, David Kuter, MD, DPhil, from the Massachusetts General Hospital, in Boston, presented long-term data from an open-label extension study out to 3 years. Platelet counts remained stable, and the incidence of severe bleeding events (≥ grade 3) declined over time, he reported. There was no evidence to suggest that the drug's stimulation of platelet production leads to an "exhaustion of the bone marrow," he commented in answer to a question from the audience.

Experts Urge Restraint While Experience Grows

However, some experts urged restraint in the use of these new drugs until more data are available and clinical experience grows. At a press conference that highlighted the new data on eltrombopag, current ASH president Kenneth Kaushansky, MD, professor of medicine at the University of California, San Diego, said: "I would be hesitant to use this new drug." Physicians are conservative in their approach to patient care, he commented, so "I would first use standard therapy with corticosteroids, then go to rituximab and splenectomy, and only then go to these new drugs," he said.

Alan Michelson, MD, from the University of Massachusetts Medical School, in Worcester, who chaired the session at which the eltrombopag data were presented, also urged caution. "These drugs should be used only by experienced hematologists and in patients who are refractory to other treatments," he told Medscape Oncology. He pointed out that both drugs were available only on a restricted program. "The safety data are good so far, but these drugs are very new, and not enough patients have been treated," he said. Nevertheless, the new data are "very exciting and these drugs represent a major breakthrough," he added.