With few treatment options and a poor prognosis, ovarian cancer represents a considerable opportunity for drug developers. Currently available chemotherapeutic agents have little impact on improving the prognosis of patients whilst ovarian cancer is one of the few indications with no approved targeted therapies. However, this may be set to change following the presentation of positive clinical trial results at ASCO. We anticipate Roche's Avastin will be approved for the first-line ovarian cancer setting in 2011, adding $1bn to the drug's sales, whilst encouraging results of Amgen's AMG386, Eisai's farletuzumab, AstraZeneca's olaparib and Sunesis voreloxin call for further development. If the early-stage promise of these first-in-class compounds is substantiated in Phase III, we would anticipate the ovarian cancer market expanding significantly during our forecast period.
- The much-awaited results of Avastin in ovarian cancer were presented yesterday in the plenary session at ASCO. The results demonstrated that treatment of newly-diagnosed ovarian cancer with chemotherapy and Avastin, followed by maintenance Avastin, significantly improved progression-free survival (PFS): The risk of progression decreased by 28% compared to chemotherapy alone.
- We anticipate these results will pave the way for approval of Avastin in both the US and EU for induction and maintenance use in the newly diagnosed ovarian cancer population. We expect that approval in this setting will add nearly $1bn in sales in 2016.
- Phase II results of Amgen's first-in-class Ang1 and Ang 2-inhibiting peptibody, AMG386, were presented today, Monday, at ASCO. Angiopoietin molecules are known to interact with Tie2 and are pivotal players in the angiogenic process. Thus, inhibition of the angiopoietin-Tie2 interaction may be a new strategy in the fight against metastatic cancer.
- The results showed that AMG 386 combined with weekly paclitaxel was highly efficacious and tolerable, with a manageable safety profile. PFS, the primary endpoint, significantly increased from 4.6 months with placebo to 7.2 months in the high-dose AMG 386 arm, suggesting further development of the compound was warranted. Phase III trials are in planning.
- Final Phase II data of farletuzumab in platinum-sensitive relapsed ovarian cancer were also presented. Farletuzumab is an antibody against folate receptor alpha, which is over-expressed in approximately 90% of ovarian cancers. The Phase II trial involved treating patients with both monotherapy and combination farletuzumab. There was a marked response to the drug, with 89% of patients exhibiting normalization of their CA-125 levels and an overall response rate (ORR) of 70%. The compound is currently being investigated in Phase III trials in the same setting.
- PARP inhibitors have been touted for their potential in BRCA-mutated and serous ovarian cancer. However, all studies to-date have only shown an effect when combined with chemotherapy. However, results presented at ASCO on Saturday demonstrated that monotherapy olaparib is also an active therapy in high-grade serous ovarian cancer, regardless of BRCA mutation status. This was shown not to be the case in breast cancer, where monotherapy olaparib did not exert an efficacious effect. This positive result has the potential to expand the PARP inhibitor market and provide another treatment option for ovarian cancer patients.
- Lastly, positive data was also reported for the first-in-class quinolone derivative voreloxin in platinum-resistant ovarian cancer. The ORR of 11%, 12 week disease control rate of 48% and PFS of 84 days was in line with results produced by pegylated liposomal doxorubicin in the same setting. Adverse events were manageable although a 9% rate of febrile neutropenia will require careful monitoring of patients. However, the great unmet need in this population of patients and encouraging efficacy data encourages further development.