Efficacy and safety of equine anti-thymocyte immunoglobulin (eATG) in three Japanese patients with moderate to very severe aplastic anemia: a case series.

Aplastic anemia results from lymphocyte-mediated destruction of hematopoietic stem cells. Immunosuppressive therapy with anti-thymocyte globulin (ATG) and cyclosporine is the standard front-line treatment for patients with severe aplastic anemia who are not suitable candidates for stem cell transplants. PF-06462700 is a potent equine ATG that targets T-lymphocytes and has been approved as a treatment for aplastic anemia outside of Japan for over 30 years. Due to the high medical need for PF-06462700, the Ministry of Health, Labor and Welfare requested its development for Japanese patients with aplastic anemia. In this case series, the efficacy and safety of PF-06462700, administered intravenously at 40 mg/kg/day for 4 days, were assessed over a 24-week period. This was as an open-label, single-arm, multicenter clinical study designed to enroll a minimum of three Japanese participants with aplastic anemia. Two participants met the primary outcome of hematologic response at week 12 and improvements in disease severity were observed. No deaths or serious adverse events were reported. The efficacy results from this case series suggest that administration of PF-06462700 is generally well-tolerated and produces a hematologic response in Japanese patients with aplastic anemia, which should be further evaluated in real-world studies.ClinicalTrials.gov identifier: NCT04350606.

A phase 2 pharmacodynamic dose-finding, safety, and efficacy study of dalteparin for pediatric venous thromboembolism treatment in children with and without cancer.

Data from registrational trials of pediatric venous thromboembolism (VTE) treatment are sparse, especially among cancer patients. We conducted a prospective, multicenter, open-label trial (NCT00952380) on dose-finding, safety, and efficacy (measured by 90-day risks of clinically relevant bleeding [CRB] and symptomatic recurrent VTE [srVTE]) of twice-daily subcutaneous dalteparin for acute VTE treatment in patients ≤18 years old. Among 38 patients (cancer, n = 26; noncancer, n = 12), median dalteparin dose requirements per kilogram varied with age but not cancer status. Risks of CRB and srVTE were <4% in cancer and noncancer subgroups. Dalteparin is an important FDA-approved treatment for pediatric VTE, particularly with cancer.

Subcutaneous DMPA vs. intramuscular DMPA: a 2-year randomized study of contraceptive efficacy and bone mineral density.

BACKGROUND: A formulation of depot medroxyprogesterone acetate (DMPA) has been developed that allows subcutaneous injection (104 mg/0.65 mL; DMPA-SC) and achieves highly effective contraception with a similar tolerability profile to intramuscular DMPA (150 mg/mL; DMPA-IM). STUDY DESIGN: This randomized, evaluator-blinded study was designed to compare efficacy, safety, and user satisfaction in women receiving DMPA-SC (n=266) or DMPA-IM (n=268) for 2 years with an option to continue for a third year. The primary objectives were to evaluate bone mineral density (BMD) changes and contraceptive efficacy after 2 years. RESULTS: A total of 225 women completed the first 2 years of this study (DMPA-SC, n=116; DMPA-IM, n=109). After 2 years of DMPA use, BMD loss was marginally smaller in the DMPA-SC group than in the DMPA-IM group at both the total hip (-3.3% and -3.6%, respectively) and lumbar spine (-4.3% and -5.0%, respectively). In those women who received DMPA during the third year, there were no statistically significant differences in BMD loss between DMPA-SC and DMPA-IM groups at the end of Year 3. Recovery of BMD was observed in the small subpopulation of women who had discontinued DMPA-SC or DMPA-IM after the second year. The 2-year treatment-failure cumulative pregnancy rate was 0% in the DMPA-SC group and 0.8% (95% confidence interval, 0.00-2.37%) in the DMPA-IM group (life-table method). Adverse events were similar in the two groups except that injection site reactions were more common in the DMPA-SC group. CONCLUSION: DMPA-SC is an effective and well-tolerated contraceptive option, providing comparable efficacy and BMD safety to DMPA-IM.