ASCAT 2024 | Disease-modifying options for SCD: recent setbacks and the need for novel therapeutic approaches

So, unfortunately, last week we have received very sad news that Pfizer is withdrawing voxelotor from the market. So that is voxelotor, and it was one of the four disease-modifying treatments available for the treatment of sickle cell disease in the United States. The others being crizanlizumab, hydroxyurea, and L-glutamine. There was another setback prior to that showing that the Phase III clinical trial of crizanlizumab for sickle cell disease did not show a significant benefit as compared to the placebo in terms of reduction of vaso-occlusive episodes.

So hydroxyurea remains by far the most important drug we have at our disposal for sickle cell disease. It has been shown over and over again that it’s very effective, that it’s relatively safe with proper monitoring, and this has been demonstrated all over the world, essentially in places like Brazil and multiple sub-Saharan African countries and Europe and the United States. And so hydroxyurea is truly the backbone of any disease-modifying treatment strategy for sickle cell disease.

Alternatives to hydroxyurea are chronic transfusions, which can be used as simple transfusions or as exchange-automated transfusions with erythrocytapheresis. And in the United States, we also can use L-glutamine, i.e. Endari, and crizanlizumab is still available in the United States, although there has been less enthusiasm, obviously, because of the findings of the clinical trial, of the Phase III trial, although I personally still think it has a role in therapy.

So unfortunately, voxelotor is now no longer an option, and we still don’t know exactly all the details, but we are aware that unfortunately, there were significant setbacks with the Phase III clinical trials, and we will know more in the incoming days and weeks. But suffice it to say is that we don’t have now many options for sickle cell disease. We’re back to almost back to square one in a sense and this means that there is an enormous need for drug development and new and other therapeutic options for individuals living with this disease.