2 research outputs found
Characterization and comparability of biosimilars: A filgrastim case of study and regulatory perspectives for Latin America
Background: Developing countries have an estimate of ten times more
approved biosimilars than developed countries. This disparity demands
the need of an objective regulation that incorporates health policies
according to the technological and economical capabilities of each
country. One of the challenges lies on the establishment of
comparability principles based on a physicochemical and biological
characterization that should determine the extent of additional
non-clinical and clinical studies. This is particularly relevant for
licensed biosimilars in developing countries, which have an extensive
clinical experience since their approval as generics, in some cases
more than a decade. To exemplify the current status of biosimilars in
Mexico, a characterization exercise was conducted on licensed
filgrastim biosimilars using pharmacopeial and extended
characterization methodologies. Results: Most of the evaluated products
complied with the pharmacopeial criteria and showed comparability in
their Critical Quality Attributes (CQAs) towards the reference product.
These results were expected in accordance with their equivalent
performance during their licensing as generics. Accordingly, a rational
approval and registration renewal scheme for biosimilars is proposed,
that considers the proper identification of CQAs and its thoroughly
evaluation using selected techniques. Conclusions: This approach
provides support to diminish uncertainty of exhibiting different
pharmacological profiles and narrows or even avoids the necessity of
comparative clinical studies. Ultimately, this proposal is intended to
improve the accessibility to high quality biosimilars in Latin America
and other developing countries
Second asymptomatic carotid surgery trial (ACST-2) : a randomised comparison of carotid artery stenting versus carotid endarterectomy
Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence.
Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362.
Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21).
Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable