Merck KGaA's brain tumour drug excites at ASCO, MS pill resubmitted

Merck KGaA's cilengitide, a novel treatment for recurrent glioblastoma, has shown promising long-term data in a Phase II study presented at the American Society of Clinical Oncology meeting in Chicago.

Cilengitide is a first-in-class integrin inhibitor which also has anti-angiogenic properties. Data from the study led by Karen Fink of Baylor University, Dallas, Texas, showed especially encouraging results for patients who received the higher of two doses tested (2000mg twice weekly rather than 500mg twice weekly).

Strikingly, over a third of these were still alive after one year and 22% after two years. Normally, the median overall survival of patients with recurrent glioblastoma is a few months with only 20% surviving for one year. Of 15 patients who received cilengitide at the higher dose for six months to 4.5 years, none experienced treatment-related severe adverse events.

Dr Fink said the data were exciting and that 10% of patients were still alive after four years. She noted that "prognosis for patients with recurrent glioblastoma is extremely poor and additional treatment options have been desperately needed for some time." Nine in 10 glioblastoma patients experience recurrence after first-line surgery, radiation therapy and chemotherapy.

The current multicentre study had a total of 66 patients who were randomised to receive one or other of two doses. Overall survival at 54 months was doubled for patients receiving the higher dose (5% versus 2.4%). There was a 34.4% reduction in risk of death with the higher dose.

Merck is now conducting a Phase III trial, CENTRIC, with cilengitide in combination with temozolimide and radiotherapy in patients with newly-diagnosed glioblastoma. The company is also investigating the agent in patients with newly-diagnosed glioblastoma multiforme and unmethylated MGMT gene promoter in a separate trial (CORE).

The CERTO trial is investigating the drug together with the company's epidermal growth factor receptor inhibitor Erbitux (cetuximab) as a first-line treatment in patients with advanced non-small cell lung cancer. A further trial, ADVANTAGE, is investigating cilengitide added to cisplatin, 5-fluorouracil and Erbitux in recurrent/metastatic squamous cell carcinomas of the head and neck. By Olwen Glynn Owen in Chicago

Oral MS drug resubmitted to FDA
Meantime, Merck has resubmitted cladribine with the US Food and Drug Administration, seven months after receiving a 'refuse to file' letter from the agency for the treatment which the Darmstadt-based group hopes will be the first oral multiple sclerosis treatment on the market.

Merck submitted a New Drug Application for cladribine at the end of September last year, two months after a filing in Europe, but in November the FDA decreed that the file was not sufficiently complete to permit a substantive review. The refiling is good news for Merck as cladribine is competing with Novartis
Gilenia (fingolimod) to get the first MS pill approved