Lonafarnib is the lead compound in a new class, called the farnesyl transferase inhibitors (FTIs), that are attracting a lot of attention as new cancer drug candidates. Farnseyl transferase is a key enzyme involved in the regulation of the growth and proliferation of cancer cells.
Inhibition of protein farnesylation alters the activity of a number of proteins important in tumour cell proliferation, including the Ras oncogene family which is involved in 90 per cent of pancreatic cancers, half of all colon tumours and 30 percent of NSCLC cases.
Schering-Plough stressed that it still plans to continue Phase II studies in other solid tumours and in leukaemia, and pointed to the fact that other compounds - specifically AstraZeneca's Iressa (gefitinib) and Roche/Genentech's Herceptin (trastuzumab) - have also failed to demonstrate a benefit in first line NSCLC.
A Standard & Poor's report said that while first-line NSCLC is a tough indication to crack, lonafarnib's failure in this setting is still a major blow."Although the drug is still being studied for leukamia, we see the absence of the lung cancer indication crimping its potential," it said. The drug had ben tipped as making more than $500 million (€394m) in annual sales, assuming it got the go-head as an NSCLC treatment.
The lack of efficacy is also disappointing for other developers of FTIs. These include Janssen-Cilag with Zarnestra (tipifarnib; R11577) and Bristol-Myers Squibb with BMS-214662.
S&P's also said that Schering-Plough's near-term prospects are "dimmed by generic erosion in the hepatitis C line and shrinkage in the allergy market," adding that the firm is "also beset by legal and compliance issues."