ORLANDO, Fla. – In an effort to get sickle cell disease (SCD) researchers, drug developers, patients and regulators all on the same page, the American Society of Hematology (ASH) and the FDA have released new recommendations aimed at establishing uniform global standards for clinical trial endpoints to evaluate new therapies.  

It's "the first-ever comprehensive look at what endpoints we have knowledge and evidence around and where there still needs to be some research," Julie Panepinto, a professor of pediatric hematology at the Medical College of Wisconsin, told BioWorld. Panepinto is co-chair of ASH’s Guideline Oversight Committee. The hope, she said, is to promote more disease-modifying therapies for sickle cell disease. 

For years, there was only one FDA-approved therapy for SCD, hydroxyurea. However, since 2017, three more have been added: Emmaus Medical Inc.'s Endari (L-glutamine oral powder), Novartis AG's Adakveo (crizanlizumab) and, just recently, Global Blood Therapeutics Inc.'s Oxbryta (voxelotor). That slow progress in the development and approval of new therapies has meant that "we haven't necessarily learned a lot about what endpoints are the best endpoints," Panepinto said. An ideal endpoint incorporates not only clinical impact, but patient perspective, too, she said. 

But progress has not been as fast as patients or their doctors would hope amid a backdrop of rapidly advancing scientific understanding, leaving endpoints used to evaluate earlier SCD treatments inadequate, FDA Division of Hematology Products Director Ann Farrell said. "These changes have greatly impacted the discussion the agency is having with the pharmaceutical industry as new clinical trials are designed," Farrell said. "We need endpoints that better reflect the patient experience of their disease in the current health care system," she said. 

The new recommendations arose out of a series of panels convened by Panepinto and Farrell and identify not only endpoints that have been commonly employed, such as pain and complementary patient-reported outcomes, but also relatively new areas of research, measurements of cure. Other areas explored by the panels include endpoints related to assessment of SCD's effect on the brain, endpoints to capture the progression of renal and cardiopulmonary disease associated with SCD, and the development and validation of a broader array of biomarkers to measure response to therapy. 

Two papers documenting the wide-ranging discussions around each potential trial endpoint were published Dec. 6 in the ASH journal Blood Advances

No Comments