Recipharm and Oncopeptides collaborate in the development of Melflufen for the treatment of multiple myeloma

What is myeloma?
Multiple myeloma (MM) is a cancer in the bone marrow that results in the production of abnormal blood plasma cells. Approximately three in every 10,000 people are diagnosed with MM each year. Despite recent advancements in therapy, MM remains incurable which has created the need for novel and safer therapies to give patients a better quality of life.

What is Oncopeptides doing to meet this need? 
As an R&D stage pharmaceutical company focused on developing drugs for the treatment of cancer, Oncopeptides has developed a product called Melflufen for the treatment of MM. As a lipophilic peptide conjugated alkylator, Melflufen rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. The compound is currently being evaluated in a phase III study with planned regulatory submission in summer 2020. Recipharm supported Oncopeptides during all steps of the pre-clinical development of Melflufen and had a consultancy role in respect to GMP activities.

What challenges did Recipharm work with Oncopeptides to overcome? 
Oncopeptides turned to Recipharm’s chemistry team to reverse engineer a batch of its molecule after a previous partner failed to meet its needs.  Poor stability of the drug product in its original solvent formulation presented challenges that could have potentially halted the project. Due to the requirement for rapid delivery to blood cells, Melflufen needs to be consumed intravenously. However, this was initially problematic as the molecule proved to be unstable in aqueous solutions and could only be formulated as a freeze-dried powder. Developing this formulation was a crucial step in the project, lasting around two years and requiring a comprehensive problem-solving approach by Recipharm’s technical team. 

What role did Recipharm’s team play during manufacturing?
The partnership with Oncopeptides saw Recipharm act as a chemical consultant which involved testing batches, analysing results, as well as looking through batch manufacturing records to identify areas for improvement. Recipharm also advised on solutions to any challenges that occurred during the development. Essentially, Recipharm acted as Oncopeptides’ chemistry, manufacturing and controls (CMC) department. 

What do Melflufen’s clinical trials involve?
More than 650 patients will be involved in the different clinical trials that are currently underway. Recipharm wrote the clinical protocols and drug handling instructions to be used by the hospital pharmacies for the trials that are commencing in the US and western Europe, as well as performing regulatory correspondence in relation to CMC with the FDA and European regulatory agencies. This sizeable project involves seven different clinical trials, see Figure 1, including a pivotal phase III trial to gather results for regulatory submission. 

Fig 1. Oncopeptides clinical development program of Melflufen. SoC (standard of care); RRMM (relapsed and refractory multiple myeloma).

Is Recipharm’s work with Oncopeptides ongoing?
Yes. Recipharm continues to support Oncopeptides with the synthesis of impurities and metabolites that will be used as reference standards in the GMP manufacturing of both drug substance and drug product. We are also the preferred supplier of the starting materials, in kg scale, for the GMP manufacturing of the API and supporting with analytical chemistry in order to have all data available for the submission.

We are also continuing to collaborate with Oncopeptides on the team’s back-up programmes which are currently in pre-clinical and clinical phases, including both analytical and synthetic chemistry support. 

What has been the overall outcome of the initial collaboration?
The collaboration between Oncopeptides and Recipharm has been pivotal in enabling the successful development of a new product to treat patients with MM. The molecule is rapidly progressing through the drug pipeline and is predicted to be particularly advantageous for late stage patients where there is considerable medical need.