Our clinical development program will provide us with a broad set of data and information about melflufen’s efficacy in various patient groups. We initiated preparations for an NDA submission based on the available HORIZON data. The overall regulatory risk will decrease considerably given that the FDA grants a conditional market approval.
The clinical development program
We are currently conducting four clinical trials to characterize melflufen in multi-refractory multiple myeloma patients: OCEAN (OP-103), HORIZON (OP-106), ANCHOR (OP-104) and BRIDGE (OP-107).
The program will provide a clear picture of how melflufen can be used for relapsed refractory multiple myeloma (RRMM) patients in various stages of the disease. This has lowered the development risk and given rise to several potential paths for obtaining approval for melflufen.
Melflufen has previously undergone both preclinical trials and clinical phase 1 and 2 trials with positive results in terms of both safety and efficacy in patients with multiple myeloma. Based on these results, the next logical step was to further develop melflufen through the trials OCEAN, HORIZON, ANCHOR and BRIDGE, and the planned additional pivotal combination trial LIGHTHOUSE.
Our phase 3 trial, OCEAN, and phase 2 trial, HORIZON, are key studies for the submission of an NDA/MAA to potentially obtain marketing authorization for melflufen in the US and the EU for the treatment of RRMM. In addition to proving melflufen’s efficacy in relation to the existing standard treatment for RRMM (meaning pomalidomide), as evaluated by OCEAN, the development program also aims to demonstrate, through HORIZON, the activity of melflufen in patients with relapsed refractory multiple myeloma whose disease is triple-class refractory (i.e. refractory to at least one IMiD, one proteasome inhibitor and one anti-CD38 monoclonal antibody). Our phase Our clinical development program will provide us with a broad set of data and information about melflufen’s efficacy in various patient groups. We initiated preparations for an NDA submission based on the available HORIZON data. The overall regulatory risk will decrease considerably given that the FDA grants a conditional market approval. 1/2 trial, ANCHOR, is aimed at demonstrating how melflufen can be administered in combination with other multiple-myeloma drugs. It is important to generate knowledge and understanding among physicians about how melflufen can be used together with dexamethasone and either bortezomib or daratumumab in relapsed refractory MM patients. BRIDGE is a phase 2 pharmacokinetic trial to study melflufen’s safety in patients with reduced renal function. We are also preparing to start a pivotal phase 3 study called LIGHTHOUSE, which is planned to start in the second half of 2019.
The regulatory path ahead
The initiated submission process in the US for accelerated approval for melflufen for the treatment of RRMM patients with triple-class refractory disease, 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 trial. Both OCEAN and LIGHTHOUSE can independently act as confirmatory trials for a potential accelerated approval. Additionally, both OCEAN and LIGHTHOUSE – assuming positive outcome from the trials – can result in broadening of the label into less advanced RRMM patient populations (both trials) as well as in combination with daratumumab (LIGHTHOUSE).
Oncopeptides has collaborated with leading experts and held discussions with governing medical agencies and professional bodies in the US and Europe 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. The program aims to fully characterize melflufen in the treatment of RRMM and thereby maximize the product candidate’s market potential.
The OCEAN pivotal phase 3 trial is expected to lay the foundation for an application to broaden the indication for melflufen late 2020. The application can act as a confirmatory trial after a potential accelerated approval – including label extension into RRMM patients with only single class refractory disease (compared to the potential accelerated approval for the treatment of RRMM patients with triple-class refractory disease) – as well as act as an independent application for market authorization across markets.
In the OCEAN clinical phase 3 trial, the efficacy of Oncopeptides’ product candidate, melflufen, is compared with pomalidomide, both are administered in combination with the steroid dexamethasone. Pomalidomide is currently the market-leading medication for the treatment of RRMM, with sales of 2.0 billion USD in 2018. The objective of the OCEAN trial is to prove that melflufen has a superior efficacy and safety profile compared with pomalidomide.
The primary read-out in OCEAN is a comparison between melflufen and pomalidomide regarding PFS (Progression Free Survival). This comparison can simplistically result in three different outcomes i.e. that melflufen is superior, non-inferior or inferior to pomalidomide. As seen in the graphic below, the non-inferior outcome can be broken down in different scenarios with stronger or weaker data to support marketing efforts of melflufen. OCEAN has been statistically powered to show superiority of melflufen over pomalidomide based on historical data for the two compounds.
A superiority outcome is expected to result in approval both in the US and the EU. A non-inferiority result is expected to result in approval in the EU and probably also in the US assuming that the forthcoming application for conditional market approval based on HORIZON data is approved by the FDA.
The planned LIGHTHOUSE pivotal phase 3 trial is designed to further broaden the indication for melflufen. The application can act as a confirmatory trial after a potential accelerated approval – including label extension where melflufen is approved also in combination with daratumumab for the treatment of RRMM patients – as well as act as an independent application for market authorization across markets.