Another option for patients with CLL or SLL
As part of Project Orbis, an international collaboration for concurrent submission and review of oncology products among international partners, the FDA has granted supplemental approval to acalabrutinib (Calquence) for adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). A kinase inhibitor, acalabrutinib is an oral drug previously approved by the FDA to treat adults with mantle cell lymphoma who have received at least one prior therapy. This additional indication provides a new treatment option for patients with CLL or SLL as an initial or subsequent therapy.
Although CLL and SLL are both cancers of lymphocytes, CLL mainly affects the blood and bone marrow whereas SLL occurs mainly in the lymph nodes. Signs and symptoms of CLL and SLL include anemia, thrombocytopenia, fatigue, lymphadenopathy, and a higher risk of infection.
The supplemental approval of acalabrutinib for patients with CLL or SLL was based on two randomized clinical trials that compared acalabrutinib to other standard treatments. In both trials, patients taking acalabrutinib experienced longer progression-free survival.
The most common adverse reactions to acalabrutinib are anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain. Teach patients to recognize and report signs and symptoms of potentially serious adverse reactions such as cardiac dysrhythmias, bleeding, and solid tumor cancers. To reduce the risk of skin cancer, which has developed in some patients taking acalabrutinib, instruct them to avoid sun exposure and use sun protection when outdoors.
Sources: US Food and Drug Administration. FDA takes second action under international collaboration, approves new treatment option for patients with chronic lymphocytic leukemia. News release. November 21, 2019. Project Orbis. www.fda.gov/about-fda/oncology-center-excellence/project-orbis.
New therapy for sickle cell disease
Voxelotor (Oxbryta) has been granted accelerated approval for treatment of sickle cell disease (SCD) in adults and children age 12 and older. A chronic, hereditary blood disorder, SCD is characterized by abnormally shaped red blood cells (RBCs) that restrict blood flow, reducing oxygen delivery to organs and tissues. During episodes of vasoocclusive crisis, patients experience extreme pain and organ damage. An estimated 100,000 people in the US have SCD.
Administered orally, voxelotor is a hemoglobin S polymerization inhibitor that helps prevent RBCs from binding together and deforming into a sickle shape. In a clinical trial involving 274 patients with SCD, the hemoglobin response rate in patients who received 1,500 mg of voxelotor was 51.1% compared with 6.5% for patients in the placebo group. Common adverse reactions were headache, diarrhea, abdominal pain, nausea, fatigue, rash, and pyrexia.
The accelerated approval program allows the FDA to approve medication for a serious condition based on evidence that it is reasonably likely to provide a clinical benefit. Further clinical trials are required to verify and describe the drug's clinical benefit.
Source: US Food and Drug Administration. FDA approves novel treatment to target abnormality in sickle cell disease. News release. November 25, 2019.
Abatacept granted breakthrough designation
The FDA has granted breakthrough therapy designation for abatacept (Orencia) for the prevention of moderate-to-severe acute graft-versus-host disease (GvHD) in patients receiving hematopoietic stem cell transplants from unrelated donors. Severe acute GvHD impacts up to 40% of patients receiving stem cell transplants from unrelated donors with a human leukocyte antigen mismatch. The breakthrough therapy designation program is intended to expedite the development and review of drugs for serious or life-threatening diseases based on preliminary clinical evidence.
Classified as a selective T-cell costimulation modulator, abatacept inhibits T-cell activation. If approved for use by the FDA, it will be the first therapy for prevention of acute GvHD. It is currently approved to treat certain arthritic conditions.
Source: Bristol-Myers Squibb. Bristol-Myers Squibb announces US FDA breakthrough therapy designation for Orencia (abatacept) to help prevent acute graft-versus-host disease, a potentially life-threatening complication after stem cell transplant. News release. December 4, 2019.
Certain antidepressants may raise the risk
To investigate the association between antidepressant (AD) use during pregnancy and the risk of gestational diabetes mellitus (GDM), researchers conducted a nested case–control study within a database that includes data on all pregnancies and children in Quebec from January 1998 to December 2015. The primary outcome measure was GDM. The researchers identified cases of GDM after week 20 of pregnancy and randomly matched them 1:10 to controls on gestational age at index date (calendar date of GDM) and year of pregnancy. AD exposure was assessed by filled prescriptions between the beginning of pregnancy and index date.
Among 20,905 cases of GDM and 209,050 matched controls, the researchers found that about 4% had been exposed to ADs. Overall, they concluded that using ADs increased the risk of developing GDM and the risk increased with duration of AD use. However, the highest risk was associated with certain ADs, specifically the serotonin norepinephrine reuptake inhibitor venlafaxine and the tricyclic AD amitriptyline. No statistically significant association was found between GDM and selective serotonin reuptake inhibitors.
Source: Dandjinou M, Sheehy O, Bérard A. Antidepressant use during pregnancy and the risk of gestational diabetes mellitus: a nested case-control study. BMJ Open. 2019;9(9):e025908.
Take drugs at bedtime to lower CVD risks
Patients are typically advised to take antihypertensive medication upon rising in the morning. Conducted within the clinical primary care setting, the Hygia Chronotherapy Trial was designed to test whether taking medication at bedtime instead would be more effective.
More than 19,000 adults with hypertension were assigned to ingest their entire daily dose of one or more antihypertension medications at bedtime (n = 9,552) or upon awakening (n = 9,532). At inclusion and at every scheduled clinic visit (at least annually) throughout the follow-up period (median, 6.3 years), ambulatory BP (ABP) monitoring was performed for 48 hours.
Over the study period, 1,752 participants experienced the primary cardiovascular disease (CVD) outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). After adjusting for significant influential characteristics, such as older age, type 2 diabetes, chronic kidney disease, smoking, and previous CVD event, researchers concluded that “routine ingestion by hypertensive patients of [one or more] prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control...and, most importantly, markedly diminished occurrence of major CVD events.”
Source: Hermida RC, Crespo JJ, Domínguez-Sarsdiña M, et al. Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial. Eur Heart J. [e-pub ahead of print Oct. 22, 2019]