Real World Clinical Experience with Oxbryta Therapy in Individuals with Sickle Cell Disease

Abstract

Background: Oxbryta is a recently approved drug for patients with Sickle Cell Disease (SCD), which decreases HbS polymerization, thus reducing red cell hemolysis and increasing hemoglobin concentration. It was first available for Expanded Access May 9, 2019 and received fast track approval for commercial use by the FDA on November 25, 2019. Objective: This analysis aims to gain insights to the real word experience for patients with SCD who are prescribed Oxbryta, identify barriers to its use, and measure health outcomes. Methods: Electronic medical records of 54 patients with SCD who were prescribed Oxbryta from January until June 2020 were reviewed and evaluated for data regarding demographics, initiation of treatment, hematological response, side effects, dosage modifications and terminal discontinuations. Results: A total of 54 patients were prescribed Oxbryta in the study period who were 96% (52/54) HbSS, and 4% HbSβ0 (2/54); 46% (25/54) male and 54% (29/54) female, and a mean age of 41 years (range 21-70). At time of initiation, 52% (28/54) of patients were taking hydroxyurea (HU). Indication for initiation of therapy was anemia and hemolysis. In this cohort, 65% of patients (35/54) were able to access drug with a mean time to obtain drug of 45 days (range 0-118 days). The most common barriers to obtaining drug were: requiring a prior authorization or appeal 9% (5/54), incomplete patient follow up 7% (4/54), missing documentation for application 6% (3/54) and high patient co-pay 6% (3/54). Of the 35 patients who started Oxbryta, 46% (16/35) experienced at least 1 side effect with 31% (11/35) reporting multiple side effects. The most common side effects reported were gastrointestinal distress (abdominal pain, nausea, vomiting and/or diarrhea) in 23% (8/35), dermatologic effects (itching and/or rash) in 17% (6/35), and experiencing an acute VOC or increase in daily pain in 11% (4/35). Twenty nine percent (10/35) of patients required a dose modification to address side effects (half who successfully continued the drug on a modified dosage), an additional 23% (8/35) of patients terminated usage of Oxbryta in response to side effects. After two to four weeks of taking Oxbryta 63% of patients had a hemoglobin increase of at least 1g/dl or greater. Conclusion: Oxbryta produces a substantial rise in hemoglobin for persons living with sickle cell and high baseline levels of hemolysis in about 60 % of patients, similarly to the results from the HOPE trial. However, there are significant barriers to access that require close follow up in the immediate period following prescription of the drug in order to minimize delays in access. Furthermore, in our cohort we observed a higher incidence of side effects than the 23% (900mg) -26% (1500mg) reported in the pivotal trial that led to its approval. While some individuals were able to be continue therapy after dose modifications, most discontinued therapy because of side effects. Figure Disclosures Minniti: CLS Behring: Consultancy; Roche: Consultancy; Emmaus: Consultancy; Forma: Consultancy; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Teutona: Membership on an entity's Board of Directors or advisory committees; Bluebird Bio: Other; Sodium Nitrate for SCD leg ulcers: Patents & Royalties.

Recent Advances in Sickle-Cell Disease Therapies: A Review of Voxelotor, Crizanlizumab, and L-glutamine

“…The most common adverse events in the HOPE trial included headache, diarrhea, and nausea [ 16 ]. In subsequent studies, side effects were similar, with headache, diarrhea, nausea, and rash, usually mild, occurring in about a quarter of patients [ 35 , 36 , 37 , 38 , 42 , 44 ]. Discontinuation of the medication due to side effects was 0–23% of patients taking voxelotor [ 34 , 35 , 36 , 37 , 42 , 43 ].…”

“…In subsequent studies, side effects were similar, with headache, diarrhea, nausea, and rash, usually mild, occurring in about a quarter of patients [ 35 , 36 , 37 , 38 , 42 , 44 ]. Discontinuation of the medication due to side effects was 0–23% of patients taking voxelotor [ 34 , 35 , 36 , 37 , 42 , 43 ]. About 15–29% of patients required dose adjustments due to side effects [ 42 , 43 ].…”

“…The literature search retrieved 236 citations, with two further articles added through bibliographies review. A total of thirty-one articles [ 12 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 ] met all inclusion criteria: six for L-glutamine [ 12 , 17 , 18 , 19 , 20 , 21 ], nine for crizanlizumab [ 14 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ], and sixteen for voxelotor [ 16 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ,…”

“…Two Phase 2a studies evaluating increases in hemoglobin in adolescents were included at both 900 mg ( n = 25) and 1500 mg ( n = 15) per day [ 36 , 37 ]. Two single-center retrospective analyses were included investigating increases in hemoglobin ( n = 17) and real-world experience of barriers to use and health outcomes ( n = 54) [ 38 , 42 ]. Two multicenter retrospective chart reviews ( n = 60 and n = 300) evaluated prescribing trends, side effects, and clinical efficacy [ 43 , 44 ].…”

“…Discontinuation of the medication due to side effects was 0–23% of patients taking voxelotor [ 34 , 35 , 36 , 37 , 42 , 43 ]. About 15–29% of patients required dose adjustments due to side effects [ 42 , 43 ]. The most common reasons cited for prescription of voxelotor were reduction in anemia, VOEs, and pain [ 44 ].…”