Last month at the ASCO meeting, Curagen (NasdaqGM: CRGN) presented results for its lead drug, CR-011, in breast cancer and melanoma patients. CR011 had activity in both indications, however, most of the drug’s value should be ascribed to the breast cancer program, which represents a huge commercial opportunity and better chances of approval.
As I previously wrote, the significance of the breast cancer trial is not only in the clinical activity of CR-011, but more importantly, the ability to identify patients who are likely to respond to the drug. By defining the right target population, Curagen could substantially improve chances of approval, shorten development time and enjoy high market acceptance.
The poster child for this strategy is Roche’s (RHHBY.PK) Herceptin, which is approved only for breast cancer patients whose tumors express Herceptin’s target, a protein called Her2. Although only ~25% of breast cancer patients are eligible for Herceptin, it has become one of the top selling oncology drugs, bringing in $4.4B in sales last year. Had Herceptin been tested in the entire breast cancer population, it would probably never have gained approval.
At ASCO, the strategy of selecting the right patients for Herceptin paid off once again, this time in gastric cancer. As part of a phase III trial, gastric cancer patients were first screened for Her2 expression and Herceptin was given only to "Her2 positive" patients. Herceptin increased survival by 2.7 month, an improvement which will likely get the drug approved for "HER2 positive" gastric cancer. This entirely new market could boost Herceptin’s annual sales by over $1B.
As an antibody based drug, CR-011 should follow the footsteps of Herceptin, because it also binds a specific protein on tumors - GPNMB. Similarly to Herceptin, CR-011’s target is expressed only in ~25% of breast cancer patients. However, CR-011 is an antibody-drug conjugate (ADC) while Herceptin is a conventional "naked" antibody. As a result, unlike Herceptin, which works by a plethora of effects (signal modulation and recruiting the immune system), CR011 exerts its activity by a single mechanism of action. This should make the process of picking the right patients even more straightforward: The expression of GPNMB on tumors.
Based on the update at ASCO, CR-011 clearly has activity in breast cancer. In addition, there are preliminary signs of a correlation between response and GPNMB expression. To get a clearer answer, investors would have to wait until year end.
Good data but small numbers
Curagen presented top line results for 18 breast cancer patients. The patient population was particularly tough to treat, with a median of four prior chemotherapy regimens in the metastatic setting. This figure excludes biologic agents and earlier stage treatments such as post or pre-operative therapies, therefore, the actual number of prior therapies patients had received was higher, probably five or six.
In terms of clinical activity, one (6%) patient achieved a confirmed partial response (a sustained reduction of at least 30% in tumor burden) and two additional patients achieved an unconfirmed partial response (a transient tumor reduction of 30% or more). Overall, some level of tumor shrinkage was observed in 9 (50%) patients.
A confirmed response rate of 6% in a phase I trial is nothing to write home about, but it is important to remember that patients were enrolled to the study regardless of whether their tumors express high levels of GPNMB. Assuming that the patients in the trial represented the overall population, most of them expressed low levels of GPNMB, or none at all, and were therefore unlikely to respond to CR-011 in the first place. In addition, the first two patients who were enrolled in the study had pre-existing nerve side effects, which deteriorated after the first treatment cycle with CR-011.
