In Mel Brooks' film The Producers, two impresarios (played by Zero Mostel and Gene Wilder) seek a theatrical flop to use as part of a tax scam. They back a tasteless off-Broadway production, Springtime for Hitler, written by a maniac Nazi sympathizer, fully expecting the show to close before the first-night interval. Unfortunately, the production succeeds resoundingly and our heroes are ruined.
Much the same situation faces the monoclonal antibody developer Imclone (p. 111). Unless Imclone's monoclonal antibody drug, cetuximab, bombs in its next colorectal cancer trial, the company could be in real trouble. Cetuximab has attracted a good deal of critical acclaim. It has proved effective in tackling colorectal cancer. One particularly difficult set of patients are those who have already failed to respond to the cytotoxic drug irinotecan. When such patients receive cetuximab as well as irinotecan, nearly a quarter of them respond positively. Results such as these convinced Bristol-Myers Squibb last year to buy a 20% stake in Imclone for $1 billion, with the promise of milestones and royalties adding another $1 billion if the drug reaches the market.
The only problem is that, according to the US Food and Drug Administration, Imclone has not shown clinically that irinotecan is really necessary in the combination treatment. From Imclone's perspective, irinotecan is indispensable. Without it (or some other compound), cetuximab falls squarely under IP held by Genentech on monoclonals against colorectal cancer (according to http://TheStreet.com). With its own colorectal antibody in development, though, Genentech has no incentive to grant Imclone a license at anything approaching reasonable terms.
The FDA argues that Imclone needs to show that cetuximab is less effective on its own than in combination with irinotecan. Imclone has conducted a small trial of the antibody alone, but the results were not significantly different from the performance of the combined regimen. Now Imclone must institute a larger trial. If cetuximab alone proves to be a wonderful drug, that could be bad news for Imclone and BMS but very good news for colorectal cancer patients and Genentech.