Alpha blockers do not increase the risk for falls, fractures, or death in the hemodialysis population, a new observational study concludes.

In phases 4 to 6 of the Japan Dialysis Outcomes and Practice Patterns (J-DOPPS) Study, 5149 patients on hemodialysis (mean age 65 years, 68% men) received anti-hypertensive drugs, including 717 patients (14%) prescribed alpha blockers such as doxazosin, bunazosin, prazosin, or urapidil. During a mean 2 years of follow-up, 247 fractures, 525 falls, and 498 deaths occurred in the overall cohort.

Multivariable analysis of the intent-to-treat population showed that patients prescribed alpha blockers had no higher risks of falls or fractures than patients not prescribed these agents, Ken Iseri, MD, PhD, of Showa University School of Medicine in Tokyo, Japan, and colleagues reported in Kidney Medicine. This result included patients at greater risk for falls due to advanced age, systolic blood pressure less than 140 mmHg, anemia, low body mass index, or large fluid removal volume.

“The face-to-face meeting with nephrologists three times per week may permit avoidance of undesirable events through achievement of optimal blood pressure management,” Dr Iseri’s team suggested. Pre-dialysis blood pressure levels were significantly higher in alpha blocker users, indicating that these agents were commonly prescribed for resistant or refractory hypertension.

Alpha blockers also conferred no higher risk for all-cause mortality in the total hemodialysis population, the investigators reported. Alpha blockers were significantly associated with a decreased risk of death among older patients (by 29%), women (32%), patients with a cardiovascular disease history (33%), and those with a pre-dialysis systolic blood pressure of 140 mmHg or greater (31%).

“We could not fully explain why this favorable effect was found only in specific hemodialysis populations, but not in total populations,” Dr Iseri’s team wrote. “However, recent studies have shown that alpha blockers may prevent cardiac remodeling and the development and progression of heart failure and have protective benefits against hyperinflammation and cytokine storm syndrome.”

Since this was an observational study of a single ethnicity and lacked data on patient strength, frailty, history of hypotension, bone mineral density, medication adherence, and other factors, more research is needed.

Alvaiz is indicated for the treatment of:

• Thrombocytopenia in adult and pediatric patients 6 years and older with persistent or chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. It should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.
• Thrombocytopenia in adult patients with chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. It should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy.
• Severe aplastic anemia in adults who have had an insufficient response to immunosuppressive therapy.

The approval was based on efficacy and safety data from clinical studies in adults (ClinicalTrials.gov Identifier: NCT00370331, NCT00102739, NCT00351468) and pediatric patients (ClinicalTrials.gov identifier: NCT01520909, NCT00908037) with persistent and chronic ITP, adults with chronic hepatitis-C associated thrombocytopenia (ClinicalTrials.gov Identifier: NCT00516321), and adults with refractory severe aplastic anemia (ClinicalTrials.gov Identifier: NCT00922883).

Alvaiz is supplied as 9mg, 18mg, 36mg, and 54mg tablets. It is not substitutable with other eltrombopag products on a milligram per milligram basis due to the observed bioavailability in studies conducted on Alvaiz.

Among 13,799 patients with type 2 diabetes and stage 1-3 CKD, the risk for composite anemia outcomes was a significant 19% lower for SGLT2i vs GLP-1 RA users, Shih-Chieh Shao, RPh, PhD, of Keelung Chang Gung Memorial Hospital in Taiwan, and colleagues reported in JAMA Network Open. SGLT2i were significantly associated with a 21% lower risk of anemia events, including hemoglobin levels less than 12g/dL in women and less than 13g/dL in men or a clinical diagnosis of anemia.

The investigators calculated that 1 additional composite anemia outcome may be prevented among every 55 patients treated with an SGLT2i for 1 year.

Follow-up data on changes in hemoglobin levels, hematocrit levels, and red blood cell counts over 3 years supported the primary analyses. Results were consistent across sex, age, HbA1c levels, eGFR levels and specific SGLT2 inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, suggesting a class effect.

Anemia treatment initiation (ie, iron, erythropoiesis-stimulating agents, or blood transfusion) occurred in similar proportions of both groups, however.

According to Dr Shao’s team, “these findings may reinforce the proposed mechanism of anemia improvement from SGLT2 inhibitor use through regulation of the hypoxia-inducible factor system and stimulation of [erythropoietin] secretion.”

Of the cohort, 12,331 patients initiated SGLT2i and 1468 initiated GLP-1 RA. Mean age was 62 years.

The Food and Drug Administration (FDA) has cleared AnemoCheck Home, an at-home hemoglobin test kit for individuals with anemia due to nutritional deficiency (iron deficiency anemia, vitamin B12 deficiency anemia, and folate deficiency anemia), sickle cell disease, and thalassemia. 

AnemoCheck Home is a single-use, disposable diagnostic test that uses a finger stick blood sample to assess hemoglobin levels. After the blood is mixed with the test solution, the user then matches the color of the sample to a provided color card; each color correlates to a hemoglobin level. 

The FDA clearance was based on studies demonstrating that the sensitivity and specificity of the color-based test were comparable to hematology analyzers used in hospitals, clinics, and commercial laboratories. AnemoCheck was also found to be more accurate than the World Health Organization (WHO) Hemoglobin Color Scale (HCS) in detecting low hemoglobin levels.

“Our team at Sanguina is proud to introduce AnemoCheck Home as a game-changer for at-home anemia testing,” said Erika Tyburski, CEO of Sanguina. “With this FDA clearance, we are excited to provide people who have anemia with a convenient, accurate, and accessible tool to monitor their hemoglobin levels at home.”

AnemoCheck Home will be available by prescription in 2024.

Positive results were announced from a phase 3 study evaluating the efficacy and safety of crovalimab in adult and pediatric patients with paroxysmal nocturnal hemoglobinuria (PNH).

Crovalimab is an investigational, novel anti-complement 5 (C5) recycling monoclonal antibody. The COMMODORE 2 study (ClinicalTrials.gov Identifier: NCT04434092) was designed to evaluate the noninferiority of crovalimab compared with eculizumab in patients with PNH who have not been previously treated with complement inhibitor therapy.

Study participants were randomly assigned 2:1 to receive either crovalimab subcutaneously every 4 weeks or eculizumab intravenously every 2 weeks. Patients who were less than 18 years of age were included in a nonrandomized treatment arm and received crovalimab subcutaneously every 4 weeks.

The coprimary endpoints were the percentage of patients who achieved transfusion avoidance (defined as patients who are packed red blood cell [pRBC] transfusion-free and do not require transfusion per protocol-specified guidelines) and the percentage of patients with hemolysis control (measured by lactate dehydrogenase of ≤1.5 x upper limit of normal), from baseline through week 25.

Findings showed crovalimab was noninferior to eculizumab for both primary endpoints. Treatment with crovalimab demonstrated disease control in PNH patients who had not been previously treated with complement inhibitors.

The favorable benefit-risk profile of crovalimab is also supported by data from the phase 3 COMMODORE 1 study (ClinicalTrials.gov Identifier: NCT04432584), which included PNH patients switching from currently approved C5 inhibitors to crovalimab.

Full study data from both trials will be presented at an upcoming medical meeting.

“People with PNH may benefit from more options to achieve robust disease control with less frequent treatment intervals,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development. “As the first global phase 3 data for crovalimab, these results emphasize its potential to address these needs. We look forward to submitting these data to regulatory authorities, bringing us one step closer to making crovalimab available for people with PNH around the world.”

Reference

Genentech announces positive data from global phase III program for crovalimab in PNH, a rare, life-threatening blood condition. News release. Genentech. Accessed February 7, 2023. https://www.businesswire.com/news/home/20230206005656/en/Genentech-Announces-Positive-Data-From-Global-Phase-III-Program-for-Crovalimab-in-PNH-a-Rare-Life-Threatening-Blood-Condition.

The Food and Drug Administration (FDA) has accepted the Biologics License Application (BLA) for crovalimab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).

Crovalimab is an investigational anti-complement 5 (C5) recycling monoclonal antibody. The BLA is supported by data from the phase 3 COMMODORE 2 study (ClinicalTrials.gov Identifier: NCT04434092), which compared crovalimab to eculizumab in patients with PNH who had not been previously treated with complement inhibitor therapy.

Study participants were randomly assigned 2:1 to receive either crovalimab subcutaneously every 4 weeks or eculizumab intravenously every 2 weeks. Patients who were less than 18 years of age were included in a nonrandomized treatment arm and received crovalimab subcutaneously every 4 weeks.

The coprimary endpoints were the percentage of patients who achieved transfusion avoidance (defined as patients who are packed red blood cell transfusion-free and do not require transfusion per protocol-specified guidelines) and the percentage of patients with hemolysis control (measured by lactate dehydrogenase of ≤1.5 x upper limit of normal), from baseline through week 25.

Crovalimab was found to be noninferior to eculizumab for both primary endpoints. Treatment with crovalimab was associated with disease control in PNH patients who had not been previously treated with complement inhibitors. The safety profile of crovalimab was comparable to eculizumab (78% vs 80% of patients experiencing an adverse event, respectively) with the most common adverse event being an infusion-related reaction.

The benefit-risk profile of crovalimab was also supported by data from the phase 3 COMMODORE 1 study (ClinicalTrials.gov Identifier: NCT04432584), which included PNH patients switching from currently approved C5 inhibitors to crovalimab.

“This filing acceptance reinforces the value of crovalimab, which was engineered to be recycled in the bloodstream with the goal of offering a sustained response while reducing treatment burden,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development. “Crovalimab could provide an option to self-administer as infrequently as every 4 weeks, thereby reducing clinic visits for people with this lifelong condition.”

HealthDay News — Directly providing prenatal iron supplements significantly improves average hematocrit levels throughout pregnancy and reduces anemia in underserved patients, according to a study published online September 1 in JAMA Network Open.

Lisa R. Thiele, MD, MPH, from the University of Texas (UT) Southwestern Medical Center in Dallas, and colleagues evaluated if providing rather than recommending supplements with iron at prenatal visits in a medically underserved community is associated with improved hematologic indices and reduced blood transfusion. The analysis included 13,910 patients who delivered between May 13 and December 13, 2020, and were provided a prenatal supplement with iron throughout pregnancy or who delivered between January 1 and August 1, 2019, before supplements were dispensed.

The researchers found that providing iron-containing prenatal supplements was associated with higher average hematocrit levels at all time points, including a mean difference of 1.27% on admission for delivery versus those who were not directly dispensed iron. Among patients only recommended supplements, 18% had anemia on admission vs 11% with iron-containing supplements dispensed (risk ratio, 0.61). After program implementation, postpartum transfusion for acute blood loss anemia was cut by one-third in patients (from 10 to 6.6 per 1000; risk ratio, 0.62).

“We can make a large impact on our patients’ health and outcomes by implementing simple interventions,” coauthor Catherine Y. Spong, MD, also from UT Southwestern Medical Center, said in a statement. “This study demonstrates the efficacy of a public health initiative to reduce maternal anemia and the most common cause of severe maternal morbidity and gives other institutions data to implement similar programs in their own populations.”

Abstract/Full Text

Elritercept is an activin receptor type IIA-Fc fusion protein designed to increase red blood cell (RBC) and platelet production by inhibiting the signaling of a subset of the transforming growth factor beta (TGF-ß) family of proteins to promote hematopoiesis. The designation is supported by data from an ongoing, open-label, phase 2 trial (ClinicalTrials.gov Identifier: NCT04419649) that is assessing the effects of elritercept in patients with very low-, low-, or intermediate-risk MDS. 

Of the 79 patients who received at least 1 dose of elritercept, 60 had completed at least 24 weeks of treatment or discontinued as of the data cut-off date. Findings showed 50% of these patients (n=30/60) achieved an overall erythroid response, meeting either modified International Working Group 2006 Hematological Improvement-Erythroid response or transfusion independence for at least 8 weeks in transfusion-dependent patients who required at least 2 RBC units transfused at baseline.

The most common treatment-emergent adverse events reported were diarrhea, dyspnea, fatigue, nausea and headache. None of these patients had progressed to acute myeloid leukemia.

“Receiving Fast Track designation for KER-050 underscores the need for novel treatment options to address the serious unmet medical needs of people living with lower-risk MDS,” said Jasbir S. Seehra, PhD, President and CEO. “We look forward to working closely with the FDA as we engage on the design of a phase 3 clinical trial evaluating KER-050 in lower-risk MDS in the first half of this year.”

The FDA’s Fast Track designation allows for expedited review of therapies that are meant to treat serious or life-threatening conditions. Generally, the designation is granted to therapies that are expected to have an impact on factors such as survival and daily functioning.

The Food and Drug Administration (FDA) has approved a single-use, disposable, on-body injector for self-administration of Empaveli^® (pegcetacoplan). Previously, the treatment was only available for subcutaneous administration using an infusion pump.

In May 2021, the FDA approved Empaveli, a complement inhibitor, for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH). The new Empaveli Injector is designed to offer greater mobility for patients during administration; it is for abdominal subcutaneous use only.

The device includes a push button to initiate the injection and a hidden needle which automatically retracts upon dose completion. Injection time is approximately 30 to 60 minutes. 

“Empaveli continues to demonstrate its potential to elevate the standard of care, including rapid and sustained improvements of PNH disease measures,”  said Peter Hillmen, MB ChB, PhD, head, rare disease advisor, Apellis. “Now, we are further enhancing the patient experience with the approval of the Empaveli Injector, an innovative and first-of-its-kind, high-volume injector.”

The Empaveli Injector is expected to be available by the end of October 2023.