Development of Ygalo®
In the late-1990s, a group of Swedish researchers based at the Karolinska Institutet developed a series of cancer fighting molecules given the series name J1 to J6 that built on research into alkylating agents undertaken by Italian scientists in the 1970s. The ‘J’ recognised the contribution of one of the lead researchers, Dr Joachim Gullbo of Uppsala University, Sweden.
The molecule ‘J1’ was identified as having the most potential to deliver higher levels of cancer fighting alkylating agents to cancer cells and was eventually given the trade name Ygalo®.
Pre-clinical research showed Ygalo® delivered significantly lower rates of tumour growth when compared to alkylating agents commonly used in cancer treatment. The overrepresentation of certain enzymes in cancer cells, including a family of enzymes known as peptidases, was identified early as the reason for Ygalo®’s ability to rapidly increase the presence of cancer fighting molecules in cancer cells.
Clinical Development Phases for Treatment of Late-stage Multiple Myeloma
Given the history of using alkylators in treating multiple myeloma, it was decided that the clinical development phase for Ygalo® would focus on late-stage multiple myeloma patients.
A Phase 2 clinical trial was undertaken with the aim of studying the efficacy and safety of Ygalo® in late-stage relapsed and refractory multiple myeloma patients. This study was conducted with the support of six collaborating institutions (in the US and Europe), including Harvard University’s Dana-Farber Cancer Institute.
Results from the Phase 2 study showed that 43% of patients were progression-free of their cancer at six months and 12.5% at twelve months. The Phase 2 study also showed a median survival time of 19 months for patients being treated with Ygalo®. This contrasts with data from other studies on the current standard of care, pomalidomide, where the median survival time is 12 months.
The Phase 2 study results also showed that when compared to available data on standard of care, Ygalo® demonstrated a significantly lower incidence of those side effects that substantially reduce the day-to-day quality of life in late-stage relapsed and refractory multiple myeloma patients.
Results of the Phase 2 clinical study were presented to the US FDA in July 2016 and the latest clinical data was presented to the European Hematology Association at its conference in Copenhagen in June 2016.
In the course of 2015, Ygalo® received Orphan Drug Status in both the US and Europe.
Pivotal Phase 3 Clinical Study
Following approval of its detailed design under the US FDA’s Special Protocol Assessment in August 2016, Ygalo® will commence a pivotal Phase 3 clinical study in the first half of 2017.
The Phase 3 study will be a randomized open head-to-head trial in late stage relapsed and refractory multiple myeloma patients with the aim of demonstrating Ygalo®’s clinical superiority over pomalidomide with statistical significance. The study has been designed to have 90% certainty of achieving its targets based on historical data for both compounds.
If the study achieves its pre-determined statistical goals in terms of efficacy and with an acceptable safety profile, Ygalo® is likely to receive marketing approval.
Further Indications for Ygalo®
Beyond the treatment of late-stage relapsed and refractory multiple myeloma, pre-clinical studies suggest that Ygalo® may also be effective in a wide range of cancer indications. Oncopeptides is currently investigating the possibility of clinical studies in the high-dose setting in conjunction with bone marrow transplantation in multiple myeloma patients, also in the treatment of amyloidosis and of non-Hodgkin’s lymphoma. All these indications are examples of where alkylating agents are currently used, and where Ygalo® is likely to show superiority.