Other Investigational Therapies for Sickle Cell Disease

Julie Kanter, MD: There are a few more therapies coming out?

Ify Osunkwo, MD, MPH: There are some new drugs in phase 2, early phase 3 that we are very excited about. I want to hear from the panelists. What have you heard? What are you guys doing? What is out there that could come to market in the next 5 years?

Biree Andemariam, MD: We have a trial, a phase 2 study that’s looking at a way to increase cyclic GMP [guanosine monophosphate]levels, which we know are important in sickle cell disease. There are at least 3 drugs in early phase, phase 2 development that are looking at that pathway. It seems that pathway is important not only in hemoglobin F production but also in the anti-adhesive pathway, depending on which drug you’re looking at. They’re all oral, and so I think those might be part of the next wave of later phase and maybe FDA-approval-quality new therapies.

Ify Osunkwo, MD, MPH: We need to go from phase 2 to phase 3, which means that these studies have to be completed, and we need to have patients enroll on study and prove that the medication either works or does not work. What’s happening in your neck of the woods with new therapy?

Matthew Heeney, MD: I think building on the idea of increasing oxygen affinity, a group, FORMA Therapeutics, has a pyruvate kinase activator, which is a small molecule allosteric activator of pyruvate kinase. What that does is it drives through the glycolytic pathway to make more pyruvate to potentially increase the health of the red blood cell, which relies on glycolysis, and also reduces 2,3-DPG [diphosphoglycerate], which will then increase oxygen affinity. This is another way of getting around at that high oxygen affinity route to potentially benefitting the disease.

Ify Osunkwo, MD, MPH: Excellent. Jules, what’s happening in your part of the world?

Julie Kanter, MD: There was a study done a while ago called the DOVE study. It was a presented at ASH [the American Society of Hematology annual meeting] several years ago, and what we found, it’s a study of prasugrel, which is a platelet inhibitor. It specifically inhibits the certain receptor on the platelet, and by doing that, the hope was we could prevent pain crises. Now, the study was a multinational study and unfortunately, it failed to show significance. It trended toward significance in adolescence, suggesting that perhaps adolescents could benefit from this platelet inhibitor. It was also notable though that they didn’t get as much platelet inhibition as we wanted. The study was not going to be redone with the same drug but instead is being studied in a different drug called ticagrelor. Ticagrelor is targeting the same platelet receptor and specifically is looking to inhibit that platelet with a little bit more inhibition, with the goal that hopefully that will show to be preventive for pain crises. That is called the HESTIA study, and it’s exciting as well.

Ify Osunkwo, MD, MPH: We have new drugs in the pipeline, and hopefully in the next 5 years we’ll have more tools in the sickle cell treatment toolbox. I want to thank everybody on behalf of the panel. We hope that you found this Peer Exchange to be useful and informative, and please feel free to reach out to us if you have any questions or need additional information. Thank you so much for being on this webinar.

Transcript edited for clarity.