Exelixis (EXEL) is starting to recuperate after last year's clash with the FDA regarding a registration trial for its lead agent, cabozantinib (cabo), in prostate cancer. The company, which still sticks to its original plan of conducting a phase III trial using pain as a primary endpoint, is expected to announce it has enrolled the first patient in the study in the coming weeks. The trial will enroll 250 patients with bone metastases who are suffering from cancer associated pain and will evaluate cabo's effect on bone scans and pain.
Exelixis will start a more traditional phase III study in prostate cancer in the coming months. The trial will recruit ~1000 patients who failed two or more approved agents and will look at overall survival as a primary endpoint.
As I previously discussed, cabo's prostate cancer program is controversial due to the dramatic resolution of bone scans in patients with bone metastases. This effect is something investors and analysts are still trying to digest, with some questioning the relevance of the observed scan resolution. Even if the drug can shrink bone metastases, which is something no other drug has been shown to do, the impact on survival is unclear due to the lack of a precedent. The only supporting evidence is Algeta's Alphadrin, a radioactive drug that targets bone mets and leads to increased survival. Moreover, prostate cancer has become an extremely crowded field with 5 new drugs that are either approved or on the verge of approval.
At ASCO 2012 (June), Exelixis is expected to present phase II results in 150 chemo-pretreated prostate cancer patients. Although the trial is a single arm study, it will provide important information on the bone met effect and its durability in a large, more homogeneous group. Nevertheless, it seems that Exelixis must show a robust effect on overall survival in order to prove cabo is effective in prostate cancer.
What the market seems to overlook is cabo's potential beyond its bone met activity and even beyond prostate cancer. There is a growing body of evidence that shows that cabo is a promising drug even when excluding the bone met effect.
Exelixis will present phase III results in medullary thyroid cancer (MTC) at ASCO, which are expected to be remarkable based top line results announced last year. As the trial was conducted under SPA (special protocol assessment), chances of approval are very high. The market opportunity in MTC is very small (~$200M WW) but the program is important as a validation of cabo's activity regardless of the bone effect. Cabo's results compare very favorably to AstraZeneca's vandetinib, which recently got FDA approval for MTC. Financially, although Exelixis will have to find a partner that can distribute the drug globally, approval in MTC will put a minimal price tag of several hundreds of millions on Exelixis. The most intriguing (and potentially problematic) effect of such approval would be off label use, especially in patients with bone mets. One drawback could be a confounding effect in randomized trials, as patients on the placebo arm could subsequently get cabo after the study.
Cabo might be effective in many other types of cancer, including lung, ovarian renal and liver cancer. So far there are only early signs of activity, but these signs make it hard to ignore the drug's broad potential. Last year, investigators reported a tiny data set of cabo in only 6 patients, 2 of which achieved partial responses (interestingly, both had lung cancer). Last month, phase II results in liver cancer included tumor shrinkage in 78% of patients and a PFS of 4.2 months. Last week, the company reported excellent activity in renal cancer patients in the form of a 28% response rate and a median PFS of 14.7 in heavily pretreated patients (64% of patients received cabo as a third line or beyond).
Taken together, these small uncontrolled data sets clearly show cabo is a promising drug beyond its bone-met effect.
Celldex – Important data in breast cancer
Celldex (CLDX) is up 80% year-to-date, thanks to positive sentiment towards its two lead programs. Celldex is one of a few biotech companies with two advanced oncology programs, which are of high demand in today's market.
The company's most advanced program is rindopepimut, a cancer vaccine for the treatment of glioblastoma multiforme (GBM), a deadly form of brain cancer. Last year, the company started a highly anticipated phase III trial for this program after overcoming several technical issues. The vaccine generated positive consistent data in 3 phase II trials, however, these were small single-arm studies.