About our research

Development of melflufen (INN melphalan flufenamide)

In the late-1990s, a group of Swedish researchers based at the Karolinska Institute 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’ recognized 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 is now called melflufen.


Pre-clinical Development

Pre-clinical research showed melflufen (INN melphalan flufenamide) 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 melflufens 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 melflufen would focus on patients with late-stage multiple myeloma.

A phase 2 clinical study was undertaken with the aim of studying the efficacy and safety of melflufen in late-stage relapsed and refractory multiple myeloma patients. This study was conducted with the support of seven collaborating institutions (in the US and Europe), including Harvard University’s Dana-Farber Cancer Institute.

Results of the phase 2 clinical study were presented to the US FDA in July 2016. Data from the ongoing studies have been presented at various conferences, the latest being the International Myeloma Workshop in September 2019.

In the course of 2015, melflufen received Orphan Drug Status in both the US and Europe.

The regulatory path ahead

The initiated filing process in the US for accelerated approval for melflufen (INN melphalan flufenamide) for the treatment of RRMM patients with triple-class refractory disease based on data from the ongoing pivotal phase 2 study called HORIZON. It is the first step in building a potential label for melflufen within myeloma. A potential accelerated approval results in a regulatory approval that later needs to be confirmed with clinical data from a randomized study. Both OCEAN and LIGHTHOUSE can independently act as confirmatory studies for a potential accelerated approval.

Oncopeptides has collaborated with leading experts and held discussions with governing medical agencies and professional bodies in the US to create the development program for melflufen in RRMM. Upon receiving approval of the phase 3 OCEAN study design through the FDA Special Protocol Assessment in August 2016, detailed preparations commenced for the development program of melflufen.

Further Indications for melflufen

Beyond the treatment of relapsed and refractory multiple myeloma, pre-clinical studies suggest that melflufen (INN melphalan flufenamide) 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 melflufen may show enhanced efficacy and/or safety.