Oncology drug lag in Japan: has it improved over the last decade?

BACKGROUND: Existing studies and statistics on the drug lag between Japan and the United States (US) for anti-cancer drugs indicate that it has decreased, whereas more drugs are left unapproved in Japan. This study aimed to quantify the impact of unapproved drugs on the drug lag. METHODS: Information on 136 anti-cancer drugs approved in the US between 2011 and 2022 was collected. The approval lag, defined as the number of days from the date of approval in the US to the date of approval in Japan, was calculated for all selected drugs, and the median was calculated using the Kaplan-Meier method. The approval lag for drugs not approved in Japan was treated as censored data. Factors potentially associated with the approval lag were explored using Cox regression analysis. RESULTS: The median approval lags for the first half-period (2011-2016) and the last half-period (2017-2022) were 961 days (2.6 years) and 1547 days (4.2 years), respectively (Log-rank test: p = 0.0687). The participation of Japan in the global pivotal trial was associated with a shorter approval lag, and new drug applications by non-Japanese companies that did not rank in the global sales top 20 were associated with a longer approval lag. CONCLUSIONS: Drug lag has not decreased over the last decade. The percentage of pivotal trials for US approval that included Japan has increased but should be further increased in the future. Japan may require a scheme to encourage smaller non-Japanese companies to include Japan in their global clinical development plan.

Volasertib as a monotherapy or in combination with azacitidine in patients with myelodysplastic syndrome, chronic myelomonocytic leukemia, or acute myeloid leukemia: summary of three phase I studies.

BACKGROUND: This report summarizes three phase I studies evaluating volasertib, a polo-like kinase inhibitor, plus azacitidine in adults with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia, or acute myeloid leukemia. METHODS: Patients received intravenous volasertib in 28-day cycles (dose-escalation schedules). In Part 1 of 1230.33 (Study 1; NCT01957644), patients received 250-350 mg volasertib on day (D)1 and D15; in Part 2, patients received different schedules [A, D1: 170 mg/m2; B, D7: 170 mg/m2; C, D1 and D7: 110 mg/m2]. In 1230.35 (Study 2; NCT02201329), patients received 200-300 mg volasertib on D1 and D15. In 1230.43 (Study 3; NCT02721875), patients received 110 mg/m2 volasertib on D1 and D8. All patients in Studies 1 and 2, and approximately half of the patients in Study 3, were scheduled to receive subcutaneous azacitidine 75 mg/m2 on D1-7. RESULTS: Overall, 22 patients were treated (17 with MDS; 12 previously untreated). Across Studies 1 and 2 (n = 21), the most common drug-related adverse events were hematological (thrombocytopenia [n = 11]; neutropenia [n = 8]). All dose-limiting toxicities were grade 4 thrombocytopenia. The only treated patient in Study 3 experienced 18 adverse events following volasertib monotherapy. Studies 1 and 2 showed preliminary activity (objective response rates: 25 and 40%). CONCLUSIONS: The safety of volasertib with azacitidine in patients with MDS was consistent with other volasertib studies. All studies were terminated prematurely following the discontinuation of volasertib for non-clinical reasons by Boehringer Ingelheim; however, safety information on volasertib plus azacitidine are of interest for future studies in other diseases.

Efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes: A randomized, double-blind, placebo-controlled trial.

AIM: To assess the efficacy and safety of empagliflozin as add-on to insulin in Japanese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: This multicentre, double-blind, parallel-group study randomized Japanese patients with T2D insufficiently controlled with insulin (1:1:1) to empagliflozin 10 mg (n=89), empagliflozin 25 mg (n=90) or placebo (n=90) for 52 weeks. The primary endpoint was change from baseline in glycated haemoglobin (HbA1c) at 16 weeks. RESULTS: At 16 weeks, empagliflozin 10 mg and 25 mg significantly decreased HbA1c: adjusted mean difference -0.92% (95% confidence interval [CI] -1.11, -0.73) and -1.00% (95% CI -1.18, -0.82; both P<0.0001) compared with placebo. This difference was maintained up to 52 weeks: adjusted mean difference at 52 weeks -0.90% (95% CI -1.09, -0.70) and -0.96% (95% CI -1.15, -0.77; both P<0.0001). At 52 weeks, significant improvements in fasting plasma glucose (adjusted mean difference -27.62 mg/dL [95% CI -36.15, -19.08] and -31.99 mg/dL [95% CI -40.35, -23.62]) and in body weight (-1.78 kg [95% CI -2.46, -1.10] and -1.92 kg [95% CI -2.58, -1.25]) were also seen with empagliflozin 10 mg and 25 mg compared with placebo (all P<0.0001). At 52 weeks, the frequency of adverse events (AEs) and serious AEs was similar in the three treatment groups; confirmed hypoglycaemia was reported slightly more in participants in the empagliflozin 10 mg and 25 mg groups (23.3% and 22.2% vs 14.4%). All hypoglycaemic events were mild in severity; no episodes required assistance. CONCLUSIONS: In Japanese patients with insufficiently controlled T2D, adding empagliflozin 10 mg or 25 mg to insulin treatment was associated with clinically meaningful reductions in HbA1c at 16 weeks and was generally well tolerated.