Escenario actual de los medicamentos biocomparables en México: posicionamiento del Colegio Mexicano de Reumatología, 2016

The present document is a position statement of the Mexican College of Rheumatology on the use of biosimilars in rheumatic diseases. This position considers that biosimilars should be considered as interchangeable, that automatic substitution without previous notice in stable patients during follow-up is not ethical, that the approval of a biosimilar should only be given after exhaustive review of preclinical and clinical data marked by Mexican regulations, that it should be clearly stated in the nomenclature of biologic drugs which is the innovator and which is the biosimilar, that it is not correct to choose a biosimilar as treatment based only on economic reasons or extrapolate indications based only on the approval of the innovator and in the absence of safety and efficacy data for the biosimilar.     

Some thoughts on drug interchangeability

Abstract

Current regulation for generic approval is based on the assessment of average bioequivalence. As indicated by the United States Food and Drug Administration (FDA), an approved generic drug can be used as a substitute for the innovative drug. FDA does not indicate that two generic copies of the same innovative drug can be used interchangeably even though they are bioequivalent to the same brand-name drug. In practice, bioequivalence between generic copies of an innovative drug is not required. However, as more generic drug products become available, it is a concern whether the approved generic drug products have the same quality and therapeutic effect as the brand-name drug product and whether they can be used safely and interchangeably. In this article, several criteria including a newly proposed criterion for assessing drug interchangeability are studied. In addition, comments on possible study designs and power calculation for sample size under a specific design are also discussed.     

The therapeutic equivalence of complex drugs

When the patent of a small molecule drug expires generics may be introduced. They are considered therapeutically equivalent once pharmaceutical equivalence (i.e. identical active substances) and bioequivalence (i.e. comparable pharmacokinetics) have been established in a cross-over volunteer study. However this generic paradigm cannot be applied to complex drugs as biologics and a number of other therapeutic modalities. For copies of biologics the European Medicine Agency and other regulatory agencies have introduced a new regulatory biosimilar pathway which mandates clinical trials to show therapeutic equivalence. However for other complex drugs such as the iron-carbohydrate drugs, low molecular weight heparins (LMWHs), liposomal drugs and the glatiramoids regulatory guidance is still mostly lacking. In this paper we will discuss (therapeutic) experience obtained so far with these different classes of 'complex drugs' and their specifics to provide scientific arguments and criteria for consideration for a regulatory framework for the market authorization for these type of drugs.     

Symposium report—Development of safe protein therapeutics: Pre-clinical, clinical and regulatory issues

The key elements of the symposium comprise the fact that for biosimilars--as opposed to generic small molecules--apart from comparable bioavailability also efficacy and safety data are required by registration authorities. Moreover, the importance of transgenic animals in efficacy and safety testing was treated as well as the different forms of immunotoxicity of biopharmaceuticals. Transgenic animals can also be used for the detection of aggregates of a biopharmaceutical. Finally, referral was made to the post-cytokine storm-incident (TGN1412)-developed first-in-human guideline, in which is prescribed that future clinical trials with biopharmaceuticals should start with a low dose, the MABEL.     

A cost-consequence analysis of the preferential use of secukinumab versus adalimumab for the treatment of psoriatic arthritis

ObjectivesTo assess the efficiency of secukinumab compared to adalimumab as first biologic treatment for psoriatic arthritis (PsA) from the Spanish National Health System (SNHS) perspective.MethodsA cost-consequence analysis of the cost and clinical response of two treatment strategies was conducted over a 2-year time horizon. A hypothetical cohort of 10 patients with PsA initiated treatment with secukinumab 150 mg (cohort A) or adalimumab 40 mg (cohort B), respectively. Patients achieving clinical response (ACR20/50/70) at week 24 continued the initial treatment, while patients with inadequate response switched to secukinumab 300 mg. Pharmacological costs were calculated based on SmPC (notified ex-factory price). The lowest cost of adalimumab biosimilar was considered. Data on clinical response were extracted from the two matching-adjusted indirect comparison (MAIC) published comparing secukinumab vs adalimumab. Results were expressed as the cost difference between the two cohorts (€, 2019) and were calculated for each clinical response criteria (ACR20/50/70) and for each MAIC. Sensitivity analysis assessed the impact of potential discounts on the cost of adalimumab while maintaining the cost of secukinumab unchanged.ResultsDepending on the MAIC used, the cost of initiating biologic treatment for PsA with secukinumab 150 mg was 18–33% lower than the one estimated for adalimumab 40 mg, for ACR20, 18–28% for ACR50, and 16–23% for ACR70 response rate. Sensitivity analysis showed that it would be necessary a discount of 40–60%, 40–65% and 50–75% over the adalimumab cost to compensate for the differences in efficacy observed for ACR20/50/70, respectively, depending on the MAIC used.ConclusionIn patients with PsA, secukinumab could be considered a more efficient first-line biologic treatment compared to adalimumab, from the SNHS perspective.     

The comparison of Filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) as a first line peripheral blood stem cell mobilization strategy in autologous hematopoieitic stem cell transplantation: A single center experience from Turkey

Objectives and aimPatients affected by hematological malignancies can often benefit from high dose chemotherapy followed by peripheral blood stem cells (PBSCs) transplantation. Different strategies have been used to mobilize an adequate number of PBSC, including granulocyte colony-stimulating factor (G-CSF) alone or chemotherapy plus G-CSF. In this study, we aimed to compare the efficacy profile of different G-CSF agents including filgrastim (Neupogen®), biosimilar filgrastim (Leucostim®) and Lenograstim (Granocyte®) on CD34⁺ mobilization in patients who underwent autologous hematopoietic stem cell transplantation (autoHSCT).Materials and methodsWe retrospectively analysed data of patients who underwent autoHSCT diagnosed with multiple myeloma (MM), Hodgkin Lymphoma (HL), non-Hodgkin Lymphoma (NHL) and others. Data for stem cell mobilization has been obtained from patients’ files. Patients who received Filgrastim (Neupogen®), biosimilar Filgrastim (Leucostim®, Group) and Lenograstim (Granocyte®) were evaluated mainly for total CD34⁺ cell count at the end of mobilization procedure.ResultsA total of 96 patients who underwent autoHSCT were retrospectively analyzed. 27 (28.2%) of the patients were female, and 69 (71.8%) were male. The diagnosis of the patients were; multiple myeloma (39 patients, 40.6%), Hodgkin Lyphoma (23 patients, 23.9%), non-Hodgkin lymphoma (16 patients, 16.6%), and others (18 patients, 18.9%). The median number of leukapheresis cycle necessary to harvest a minimal count of 3 × 10⁶ CD34⁺/kg was 2 in Neupogen® (min–max: 1–4) and Granocyte® (min–max: 1–3) groups and 1 (min–max: 1–2) in Leucostim® group. The median doses of G-CSF agents (μg/kg/day) in PBSC collection procedure were; 10.00 (min–max: 7.00–12.00) in the Neupogen® group, 8.00 (min–max: 7.25–9.00) in the Leucostim® group and 8.50 (6.00–9.50) in the Granocyte® group. There was no statistical significance among groups (p = 0.067). The number of total collected PB CD34⁺ cells (×10⁶/kg) was 7.64 (min–max: 4.09–13.86) in the Neupogen® group, 13.43 (min–max: 8.15–23.38) in the Leucostim® group and 5.45 (min–max: 4.28–9.40) in the Granocyte® group. The data showed that patients in the leucostim group had significantly higher PB CD34⁺ cells compared to patients in the Granocyte® group (p = 0.013).ConclusionLeucostim® was comparable to Neupogen® for PBSC mobilization in patients who underwent autoHSCT.     

A Consistency Approach for Evaluation of Biosimilar Products

Recently, biosimilars have attracted much attention from sponsors and regulatory authorities, while patents on early biological products will soon expire in the next few years. The European Medicines Agency (EMEA) of the European Union (EU) published a guideline on similar biological medicinal products for approval of these products in 2005 European Medicines Agency . ( 2005 ). Guideline on Similar Biological Medicinal Products. The European Medicines Agency Evaluation of Medicines for Human Use. EMEA/CHMP/437/04. London: EMEA. Available at: http://www.emea.europa.eu/docs/en_GB/document-library/Scientific_guideline/2009/09/WC500003517.pdf  [Google Scholar]. Based on the foundational principles of the EMEA guideline, biosimilars are expected to be similar, not identical, to the innovator biologics they seek to copy. In this article, we develop a consistency approach for assessment of similarity between a biosimilar product and the innovator biologic. A method for sample size determination for conducting a clinical trial to assess the biosimilar product is also proposed. A numerical example is given to illustrate applications of the proposed approach in different scenarios.