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Ben Comer reports on how new pipeline therapies, public research investments, and a renewed sociopolitical focus are working toward a happier outcome for sickle cell disease patients.
The first act in the story of sickle cell disease, one of the oldest known genetic diseases, is not a happy one. Aside from a very small number of young patients undergoing successful bone marrow or stem cell transplants, there is no curative treatment. Other drugs address the disease according to which symptoms present most urgently, or serve as short-term solutions for a long-term problem.
Sickle cell disease prevents one of the body's most fundamental resources—the blood—from adequately transporting oxygen to the tissue, which can result in organ damage and many other related complications. A sickle cell related vaso-occlusive "crisis" can be extremely painful for patients, and deadly in some cases. Both quality of life and life expectancy are reduced for sickle cell patients, even when the disease is optimally managed with existing therapies, blood transfusions, vitamin regimens and a host of other precautions.
Beyond the medical pathology of the disease, sickle cell patients in the US—a population of 100,000—also face a social stigma. They often require strong opioids, and the disease is commonly recognized as a "black disease," or one that only plagues minorities, which isn't true. The intermittent pain crises that most patients experience usually result in an overnight stay at the hospital and a heavy dose of pain meds. Once stabilized, they return home until the next crisis strikes.
However, a quorum made of new pipeline therapies, public research investments, and a renewed sociopolitical focus on the disease is attempting to pen a redemptive second act for sickle cell patients. With a successful Phase 1 safety study completed, Abraham Abuchowski and Glenn Kazo, who serve as CEO and president of Prolong Pharmaceuticals, respectively, are currently working with sickle cell patient associations and foundations to determine which efficacy studies would have the largest impact on sickle cell patients' co-morbidities, and their lives in general.
In February, a Sickle Cell Disease Congressional Caucus was formed, led by Charles Rangel (D-NY), Danny Davis (D-IL) and Tim Scott (R-SC). The stated goal of the caucus is to "increase support for the largely under-funded disease" and to "address barriers in access to and development of crucial treatments."
Also in February, FDA convened its fifth Patient-Focused Drug Development meeting, this time on the subject of sickle cell disease. At the meeting, patients were asked to speak openly about treatment options for sickle cell, and also which effects of the disease matter most. Kazo, who attending the meeting, says two key messages emerged from those discussions. The first is that "drug development in the sickle cell area doesn't usually look at co-morbidities, or the related diseases that sickle cell patients actually suffer from," says Kazo. "The other challenge is enrolling patients in clinical studies."
Prolong's approach to sickle cell is to improve overall oxygenation, which gets at the underlying disorder in sickle cell disease. The company's lead product, Sanguinate, is an infused bovine pegylated hemoglobin molecule that Prolong hopes will address the most severe complications facing sickle cell patients. Abuchowski, Prolong's CEO, was instrumental in the development of pegylation technology decades ago, but back then the oxygen delivery characteristics of the hemoglobin protein, human or animal, weren't well understood. Plus, errant hemoglobin in the blood stream is toxic, as any clinician will tell you.
What's special about cow hemoglobin? Aside from obvious sourcing problems related to the need for large quantities of human blood, Abuchowski says human hemoglobin is extremely unstable compared to bovine hemoglobin; what makes hemoglobin especially toxic in the blood is when it splits apart. "Hemoglobin is a four sub-unit protein...those sub-units break apart in human hemoglobin, but in bovine they do not," says Abuchowski. "In the genetic engineering space, everybody thought anything human is best, but that's just anthropomorphic egotism. Just because it's human doesn't make it the best."
Prolong's Sanguinate, a play and reversal on the verb exsanguinate (defined as the action or process of losing blood), isn't being positioned as a blood substitute, which Kazo describes as a fool's errand. But Prolong will attempt to distinguish Sanguinate from other products in development by going beyond the treatment of a single symptom to address co-morbidities related to poor oxygen delivery, the root cause of vaso-occlusive crisis and many other debilitating effects of sickle cell disease.
Nearly 150 open studies targeting sickle cell disease are currently listed at ClinicalTrials.gov, underscoring patient need and industry's interest in addressing it. For patients and their families, a truly disease-modifying therapy could hold the curtain up long enough for a third and final act: the cure.
Ben Comer is Pharm Exec's Senior Editor. He can be reached at email@example.com.