Key market catalysts in the fourth quarter of 2012 include an expected decision by the US Food and Drug Administration (FDA) on the approval of cabozantinib for thyroid cancer; top-line results from a trial of re-treatment with the peptide NX-1207 in benign prostatic hypertrophy (BPH); and top-line results from Abbott's Phase II AVIATOR trial examining various interferon-free regimens for the treatment of hepatitis C virus (HCV) infection.

Cabozantinib (developed by Exelixis) is a small-molecule inhibitor of the following tyrosine kinases: rearranged during transfection (RET), vascular endothelial growth factor receptor, CD117 (also known as KIT), FMS-like tyrosine kinase 3, the angiopoietin receptor TIE2 and hepatocyte growth factor receptor (also known as MET). Treatment with cabozantinib has provided promising results in several cancer types, among which development in thyroid cancer is the most advanced. In patients with unresectable, locally advanced or metastatic medullary thyroid cancer and documented evidence of recent progression, cabozantinib provided progression-free survival (PFS) of 11.2 months compared to 4.0 months for placebo (hazard ratio (HR) = 0.28), and an overall response rate (ORR) of 28%, but no improvement on overall survival as of the interim analysis. The most recent drug to be approved by the FDA for medullary thyroid cancer, vandetanib in 2011, provided a PFS HR of 0.35, an ORR of 44% and no significant difference in overall survival relative to placebo. In August, the FDA cancelled an advisory committee meeting associated with this marketing application for cabozantinib, which we consider to be a favourable indicator for a potential approval decision; the Prescription Drug User Fee Act (PDUFA) date is 29 November.

NX-1207 (developed by Nymox) is a peptide with an undisclosed pro-apoptotic target being evaluated in BPH and in early-stage, low-risk prostate cancer. Administration involves a single intraprostatic injection. In the NX02-0016 Phase II trial, the average 90-day improvement in American Urology Association BPH Symptom Score relative to baseline was 9.7 versus 4.1 for the active control finasteride. In long-term follow-up studies, 36% of NX-1207-treated patients required no further medical or surgical treatment 52–56 months post-treatment. In the fourth quarter of 2012, Nymox is expected to report the results of a 250-patient open-label trial in patients desiring a second injection 1–7 years after the first. This release is expected to substantially expand the publicly disclosed data set around the safety and efficacy of NX-1207 in BPH.

Abbott is expected to release data from a Phase II trial (known as AVIATOR) of interferon-free regimens for HCV at the American Association for the Study of Liver Diseases (AASLD) meeting between 9 and 13 November. Abbott has previously reported that the combination of the HCV protease inhibitor ABT-450, the HCV non-nucleoside polymerase inhibitor ABT-333 and ribavirin provided a sustained viral response in 95% of treatment-naive genotype 1 patients (the most common genotype in the United States) and 47% of treatment-experienced patients in a small Phase II trial known as COPILOT. The AVIATOR trial is examining interferon-free combinations of ritonavir-boosted ABT-450 (ABT-450/r) with two or three additional drugs, including: ABT-450/r, ABT-267, ABT-333 and ribavirin; ABT-450/r, ABT-333 and ribavirin; ABT-450/r, ABT-267 and ribavirin; and ABT-450/r, ABT-267 and ABT-333. The safety and efficacy of these combinations will be examined in both treatment-naive and treatment-experienced patients. The results will provide a clearer picture of the requirements for developing interferon-free regimens, and of the competitive profile of the Abbott combinations, compared with nucleoside-based treatment regimens being developed by Gilead.