Upcoming events: Alchemia in colorectal cancer and Amgen in ovarian disease
Welcome to your weekly digest of approaching regulatory and clinical readouts. Phase III data on Alchemia’s reformulated irinotecan in colorectal cancer and full data from Amgen’s ovarian cancer drug trebananib are two approaching catalysts for the pharma sector.
For Alchemia, the data could serve to validate a platform of targeted chemotherapy agents and drive significant investment interest. Meanwhile, Amgen’s trebananib needs full overall survival data in recurrent disease to get regulatory authorisation – its success in achieving progression-free survival (PFS) gives promise of leaping that hurdle.
Alchemia has combined irinotecan with hyaluronic acid to create a chemotherapy that acts more specifically on tumour cells. Hyaluronic acid binds to the activated receptor CD44, which is frequently expressed on diseased cells but not healthy tissues. HA-Irinotecan is the Australian company’s name for its new product.
In colorectal cancer treatment irinotecan is typically included in a regimen called FOLFIRI, with leucovorin and fluorouracil. The key trial compares standard FOLFIRI against a similar combination containing HA-Irinotecan in second or third-line metastatic disease, with the goal of extending PFS.
The FOLF(HA)iri trial began recruiting patients in 2011 and completed enrolment in February 2013. Success would provide some validation for Alchemia’s HyACT technology, which the group uses to combine hyaluronic acid with numerous systemic chemotherapies – and, as such, the outcome will drive some significant share price movement.
In the clinic Alchemia has HA-Doxorubicin and HA-5FU, 5FU being another name for fluorouracil. HA-Irinotecan is also being studied in small-cell lung cancer, and a second colorectal trial is under way, but this is investigator-led. If FOLF(HA)iri is successful, Alchemia plans to file for US and European approvals in the first half of 2015.
Alchemia has also created HyACT versions of the chemotherapies gemcitabine, vinorelbine and carboplatin, along with Avastin, but has not tested any of them in humans yet.
Another cancer project most also prove its worth in the clinic. Amgen's trebananib, which arrests cancer’s spread by blocking the proteins angiopoietin 1 and 2 and restricting blood supply to tumours, has already shown significant PFS improvements in recurrent ovarian cancer, but in this disease overall survival (OS) remains the litmus test. OS data from the Trinova-1 trial will be crucial to the agent's future.
The PFS data from Trinova-1, released a year ago, suggest the potential: 7.2 months versus 5.4 months for placebo, with a 34% reduction in the risk of disease progression (Amgen clears first phase III hurdle in ovarian cancer, June 13, 2013).
Still, at the time, analysts from Bank of America-Merrill Lynch wrote that an early imbalance in deaths and a high discontinuation rate, raised questions over whether the PFS benefit could be maintained in an OS analysis. In Trinova-1 there was a numerical improvement in median OS favouring trebananib, but this was not statistically significant.
Forecasts for the project remain modest, as they do for all ovarian cancer agents: EvaluatePharma’s consensus puts sales at $52m for Amgen’s candidate in 2020. Several other clinical-stage treatments are queuing up to enter the space, led by AstraZeneca’s PARP inhibitor Lynparza, Tesaro’s niraparib and Clovis Oncology’s rucaparib. Taken together with Avastin, already authorised in the space, all pharma sales in ovarian cancer are forecast to amount to $2.49bn in 2020.
|FOLF(HA)iri||390 patients with metastatic colorectal cancer||NCT01290783|
|Trinova-1||919 patients with recurrent ovarian cancer||NCT01204749|