Use of biosimilars in inflammatory bowel disease: Statements of the Italian Group for Inflammatory Bowel Disease

The introduction of biological therapies, particularly anti-TNFα agents, has revolutionized the management of inflammatory bowel disease in those cases which are refractory to conventional treatment; however these drugs are not risk-free and their use has substantially increased the cost of treatment. As marketing protection expires for original, first-generation biopharmaceuticals, lower-cost “copies” of these drugs produced by competitor companies—referred to as biosimilars—are already entering the market. In September 2013, the European Medicines Agency approved two infliximab biosimilars for treatment of adult and paediatric inflammatory bowel disease patients, a decision based largely on efficacy and safety data generated in studies of patients with ankylosing spondylitis and rheumatoid arthritis. For many clinicians, extrapolation practices and the general question of interchangeability between biosimilars and reference biologics are cause for concern. In the present paper, the Italian Group for inflammatory bowel disease presents its statements on these issues, with emphasis on the peculiar clinical characteristics of inflammatory bowel disease and the importance of providing physicians and patients with adequate information and guarantees on the safety and efficacy of these new drugs in the specific setting of inflammatory bowel disease.     

Comparative subcutaneous repeated toxicity study of enoxaparin products in rats

Enoxaparin is a low-molecular-weight heparin widely used for the prevention and treatment of thromboembolism. With the development of several enoxaparin biosimilars, real medical concerns about their safety and efficacy have been raised. This repeated dose toxicity study consists of preclinical toxicological evaluation of a biosimilar biological version of enoxaparin, the drug product “Enoxa”, compared to the enoxaparin reference drug product, “Lovenox”. Eighty white Wistar rats were treated with “Enoxa” versus the reference product, using subcutaneous therapeutic and toxic doses, varying from 3.5 to 100 mg/kg/day. Dose levels were adjusted and ultimately fixed at 3.5 and 20 mg/kg/day as therapeutic and toxic doses, respectively. A sodium chloride solution (0.9%) was used as the control, and the comparative study was conducted over periods of 14 and 28 days. Comparable effects were observed with few adverse effects at the administration dose of 20 mg/kg/day, for both enoxaparin biosimilar and reference products. Interestingly, mortality started only at high doses of 40 mg/kg/day and reached 25% at 100 mg/kg/day for both products. These results, as part of the recommended biosimilarity monitoring, demonstrated comparable toxicity profiles of “Enoxa” and “Lovenox” products in rats. Continuing investigation of biosimilarity on humans to confirm safety and efficacy is suggested.     

Biosimilars: it's not as simple as cost alone

Background: Biosimilars or follow‐on biologics (FoB) are biopharmaceuticals that, unlike small molecule generic products, are copies of larger, much more complex proteins. As such, data generated from one biopharmaceutical cannot be extrapolated to another. Unlike small molecule generics, FoB require a full developmental programme, albeit smaller than for an originator product. This has been recognized by European regulatory authorities and it is becoming clear that accelerated processes for FoB marketing approval are not feasible. Objective: To determine the balance between costs surrounding FoB (including relatively extensive developmental programmes and subsequent price to the market) and the necessity to ensure efficacy and safety. Principal findings: It is important that FoB are sufficiently tested to ensure patient safety is not compromised. Conducting such a development programme followed by sound pharmacovigilance is very challenging and costly. Conclusions: Cost‐savings associated with FoB may be limited.     

Biosimilar biologic drugs: a new frontier in medical care

Physicians in training are expected to be aware of the newest developments in patient care. Biologic therapies have changed treatment of many diseases by specifically targeting key disease mediators, but patient access to these therapies can be limited. As patents for the first biologic therapies are expiring, the development and approval of products known as biosimilars is rapidly gaining momentum. A biosimilar is a biologic product that is highly similar to a reference product (a licensed biologic product), notwithstanding minor differences in clinically inactive components. Biosimilars undergo a thorough evaluation compared with the licensed biologic and need to demonstrate comparable clinical pharmacokinetics, efficacy, and safety including immunogenicity. Understanding the processes for new drug approvals, the rigorous evaluation of biosimilars, and considerations about their selection and use can help recently trained physicians to make informed treatment decisions and improve patient outcomes.     

Biosimilar filgrastim (leucostim®) have similar efficacy in steady-state hematopoietic progenitor cell mobilization compared to original filgrastim (neupogen®) and lenograstim (granocyte®): A retrospective multicenter study

Biosimilar filgrastim (Leucostim^®) was shown to be similar in terms of efficacy and safety in hematopoietic progenitor cell mobilization (HPCM) compared to originator filgrastim (Neupogen^®) and lenograstim (Granocyte^®) in healthy donors and chemomobilization settings. Here we report our retrospective experience with Leucostim^® (n: 43) compared to Neupogen^® (n: 71) and Granocyte^® (n: 32) in steady-state mobilization of patients presenting with Hodgkin lymphoma, non-Hodgkin lymphoma and multiple myeloma. The median age of patients on Leucostim^® (56) arm was significantly higher compared to patients who received Neupogen^® (50) and Granocyte^® (49) (p: 0.039). Patients who underwent HPCM with Leucostim^® received less chemotherapy lines (p: 0.026) and courses (p: 0.046) compared to others. Otherwise the study cohort was homogenous in terms of gender, primary diagnosis and various risk factors for mobilization failure. Mobilization failure was defined as failure to achieve a minimum threshold (10/μL) for peripheral blood CD34⁺ cell concentration to initiate leukapheresis or 0.5 × 10⁶/kg, 0.8 × 10⁶/kg and 2 × 10⁶/kg CD34⁺ cells in first, second and fourth days of apheresis, respectively. The study groups were similar in terms of median number of CD34⁺ progenitor cell yield ( × 10⁶/kg) (Neupogen^®: 6.18, Granocyte^®: 6.2 and Leucostim^®: 6.2) (p: 0.959) and median number of leukapheresis sessions (p: 0.615). The treatment arms were also similar in terms of mobilization failure (Neupogen^® 11.3% ? Granocyte^® 21.9% ? Leucostim^® 16.3%; p: 0.366). No patient experienced any severe adverse effect during HPCM. Leucostim^® is equally effective and safe in HPCM compared to originator G-CSF (Neupogen^®) and lenograstim (Granocyte^®) in steady-state HPCM setting.     

Use of biosimilars in inflammatory bowel disease: a position update of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD)

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars.