The DEEP Project has already brought forth its first results and is continuing along the challenging path of a large multinational clinical trial. At this point, which is now in the final stage, we asked Dr. Michale Spino, President of ApoPharma Inc. to describe the major contribution provided by ApoPharma, one of the project partner, in the fulfillment of the project and what contribution could still be provided.
“The scope and objectives of the studies were recognized by all of us to be challenging, but the complexities, particularly of DEEP-2, the randomized controlled trial comparing deferiprone and deferasirox in the treatment of iron overload in children with hemoglobinopathies, exceeded expectations. That the obstacles have now been overcome, albeit with much work over a longer period than we might have wished for, is due to the DEEP Management Team’s relentless local effort and experience, the trials’ dedicated clinical investigators, and ApoPharma’s knowledge and expertise in conducting clinical studies in many different countries. With DEEP-2 – he pointed out – the company has aimed to be a full partner in study design, logistics, and regulatory and pharmacovigilance interactions from the outset. Two ongoing relationships have been particularly noteworthy: one the collegial scientific and medical discourse among ApoPharma, DEEP HQ staff, investigators and contractors, and the other the friendships built mostly by email between ApoPharma and DEEP team members in managing the challenges of product supply to multiple sites on two continents. As we come to the end of the extended DEEP 2 enrolment, and the explosion in recruitment in recent months, ApoPharma has been asked to continue its supply of deferiprone to fund treatment of the many patients who still have only a little less than a year left on study. We have also been requested to cover the financial shortfall that is a natural accompaniment to this delayed take-off, and especially to help purchase deferasirox, the expensive comparator specified by PDCO. We have agreed to both in the interests of everyone involved in the study, from scientists and investigators to the young patients”.
Regarding the application for Market Authorization in 2017, Dr. Spino explained that “assuming that the data reveal that deferiprone is non-inferior to deferasirox in this population, ApoPharma intends to file a Marketing Authorization for pediatric use in the control of iron overload in children. A 2017 target is probably optimistic, with the last patient, last visit likely to occur after the end of the first quarter of that year, a huge quantity of data to review and evaluate, a substantial, submission-ready report to produce, and the PUMA itself to prepare. The many investigators involved in the study are of varied experience in the complexities of large GCP studies. Questions, and the resulting delays, will be inevitable, but overcoming the challenges to complete this study will bring tremendous satisfaction to all participants. If the submission timeline extends into 2018 but its quality is commensurately increased, that is an acceptable trade-off. Clearly, the DEEP studies will be required for obtaining EU approval, but will constitute only part of the submission. We look forward to a joint meeting among PDCO, CHMP, DEEP and ApoPharma to understand what is needed, and how best to put it in place with minimum delay to obtain Marketing Authorization.“
We have further discussed with Dr. Spino the added value that the DEEP project can bring in terms of market impact and if it will provide a competitive advantage compared to the other chelators available on the market. He stated that “The DEEP-1 study has already provided unique information, i.e., that the pharmacokinetics of deferiprone in children and adults are comparable, and hence that doses on a per kg body weight basis can be standardized. While this was anticipated, it had not been proven. DEEP-2, as the first RCT of deferiprone and deferasirox in children, is the second major contributor to advancing understanding of chelator selection in a paediatric population. Although some studies have been conducted comparing the two oral chelators, there have been no large RCTs. If non-inferiority is demonstrated, then the confidence of clinicians to choose whichever chelator is most suited to a particular patient will be enhanced. Greater freedom to prescribe optimal chelation therapy is good for the patients, and in the long run should benefit ApoPharma as well”.