The results reported by GlaxoSmithKline in phase II studies of eltrombopag, SB-497115, a small-molecule drug that mimics the activity of thrombopoietin (TPO), a protein factor that promotes growth and production of blood platelets, were promising.

On November 30, 2005, during a review of its oncology portfolio, GSK presented data from a phase II dose-ranging clinical trial that showed 115 significantly raised platelet counts in adult patients. GSK described the phase II studies well underway in three major indications: idiopathic thrombocytopenia purpura (ITP), hepatitis C (HCV) and chemotherapy-induced thrombocytopenia (CIT), states a company release.

The phase II results in adult patients with chronic ITP that had failed at least one prior therapy and with platelet counts less than 30,000 showed that 66% of the patients receiving the 50 mg dose and 87% of patients treated with 115's highest dose (75 mg/day) had counts greater than or equal to 50,000 after six weeks and many of those had reached normal platelet levels within the first two to three weeks of treatment.

In comparison, only 13% of placebo-treated patients showed platelet increases greater than or equal to 50,000 after six weeks. The frequency of side effects was comparable between patients treated with placebo and those treated with eltrombopag. Additional data presented at the meeting showed encouraging results in an interim analysis in a phase II study in HCV patients.

"We are pleased to see that our vision of the early 1990's of the emergence of an exciting, new TPO pharmaceutical market is now rapidly being translated to concrete product assets with great potential to meet unmet patient needs and for shareholder value. The assets eltrombopag and SB-539448 resulted from a collaboration agreement GSK entered into with Ligand in 1995, and which incorporated TPO as a target in 1997 while an internal programme initiated following completion of the collaborative programme has produced LGD4665, now targeted for IND filing in the first half of 2006," said David E. Robinson, chairman, president and chief executive officer of Ligand Pharmaceuticals.

"We believe the size and potential of the emerging thrombocytopenia market will clearly support multiple once-a-day oral product entries and therefore have made LGD4665 our top new chemical entity product development priority," added Robinson.

The release further informs that in February 2005, Ligand earned a $1 million milestone payment from GSK with the company's commencement of phase II trials for eltrombopag. If the drug continues in development and ultimately is approved and marketed, Ligand could receive additional milestone payments and royalties on net product sales.

"GSK's efficacy and safety data from both phase II studies is impressive, confirming and extending previously presented phase I data in normal volunteers to two distinct patient populations (ITP and HCV) with chronic thrombocytopenia. The data further highlights the promising nature of the oral TPO mimic programme jointly initiated in 1997 by GSK and Ligand," said Andres Negro-Vilar, Ligand's executive vice president of research and development and chief scientific officer.

Ligand has its own TPO-mimic oral drug candidate, LGD4665, in preclinical development and plans to file an IND in the first half of 2006. This candidate was selected from a group of novel oral mimics synthesized at Ligand. These molecules were profiled to have in vitro efficacy and selectivity equal to or better than TPO in predictive human cell models and to have a better profile of efficacy and potency than other oral mimics currently in clinical development.

"We are very excited about LGD4665's profile of potency and efficacy as important characteristics of a follow-up product in a large, underserved market. The two principal targets for clinical development are currently chemotherapy-induced thrombocytopenia and liver disease-induced thrombocytopenia, which represent the two largest market segments for drugs of this type," said Dr. Negro-Vilar.

Ligand discovers, develops and markets new drugs that address critical unmet medical needs of patients in the areas of cancer, pain, skin diseases, men's and women's hormone-related diseases, osteoporosis, metabolic disorders, and cardiovascular and inflammatory diseases.