Biosimilar Research Articles

Forced Degradation Testing as Complementary Tool for Biosimilarity Assessment.

Oxidation of monoclonal antibodies (mAbs) can impact their efficacy and may therefore represent critical quality attributes (CQA) that require evaluation. To complement classical CQA, bevacizumab and infliximab were subjected to oxidative stress by H2O2 for 24, 48, or 72 h to probe their oxidation susceptibility. For investigation, a middle-up approach was used utilizing liquid chromatography hyphenated with mass spectrometry (LC-QTOF-MS). In both mAbs, the Fc/2 subunit was completely oxidized. Additional oxidations were found in the light chain (LC) and in the Fd’ subunit of infliximab, but not in bevacizumab. By direct comparison of methionine positions, the oxidized residues in infliximab were assigned to M55 in LC and M18 in Fd’. The forced oxidation approach was further exploited for comparison of respective biosimilar products. Both for bevacizumab and infliximab, comparison of posttranslational modification profiles demonstrated high similarity of the unstressed reference product (RP) and the biosimilar (BS). However, for bevacizumab, comparison after forced oxidation revealed a higher susceptibility of the BS compared to the RP. It may thus be considered a useful tool for biopharmaceutical engineering, biosimilarity assessment, as well as for quality control of protein drugs.

Biosimilar for teriparatide safe and effective.

Biosimilar for teriparatide safe and effective.

CT-P13 biosimilar is non-inferior to infliximab.

CT-P13 biosimilar is non-inferior to infliximab.

New & Approved: New approvals, formulations, indications, generics, biosimilar

New & Approved: New approvals, formulations, indications, generics, biosimilar

PMU61 VARIABLE BIOSIMILAR COVERAGE ACROSS US COMMERCIAL PLANS

There are several biosimilar/follow-on biologics available in the US, however the level of coverage by commercial plans, and therefore uptake, has been significantly lower than expected. This research examines their coverage by US commercial healthcare plans. Nine of the largest commercial healthcare plan providers in the US were selected, and their publicly-available coverage of ten biosimilar/follow-on biologics along with the seven reference brands was assessed on 16/01/2019. Biologic copies that underwent approval via the abbreviated biosimilar pathway 351(k) as well as the 505(b)(2) new drug approvals pathway were included. The biosimilar/follow-on biologic with the highest level of commercial plan coverage is Sandoz’s Zarxio® (filgrastim-sndz), with 9/9 plans providing coverage, 6/9 (67%) of which also list Zarxio® as a preferred choice over the originator Neupogen® (preferred by 2/9). In contrast, the Remicade® brand has remained a preferred choice among 4/9 (44%) of plans, with the two available biosimilars Inflectra® and Renflexis® preferred by only 1/9 of the plans each. Interestingly, the two available follow-on insulin products, Admelog® (insulin lispro) and Basaglar® (insulin glargine) are viewed distinctly, with Basaglar® being preferred in 5/9 (56%) of plans compared to the originator Lantus® (4/9, 44%), while Admelog® is preferred by only 1/9 plans, versus 6/9 (67%) for the originator Humalog®. The level of biosimilar/follow-on biologic coverage was variable: some plans preferred to maintain access to the branded biologic despite biosimilar availability, while others were incentivized to switch coverage to a biosimilar. Following biosimilar launch, there are often further price negotiations, confidential discounts, and exclusivity contracts taking place between manufacturers and healthcare providers, which influence and shape formulary access. The distinct experiences of the different insulin follow-on biologics emphasize that this step is critical for their commercial success.

Biosimilar to Infliximab Is Effective for Inducing Remission in Crohn Disease

Because CT-P13, a biosimilar to originator infliximab, was approved for treating Crohn disease based on extrapolation of efficacy in rheumatoid

P071 Supporting extrapolation of indications for ABP 501, the first adalimumab biosimilar: focus on Crohn’s disease

P071 Supporting extrapolation of indications for ABP 501, the first adalimumab biosimilar: focus on Crohn’s disease

The Case for Disclosure of Biologics Manufacturing Information.

Ten years after the enactment of the Biologics Price Competition and Innovation Act (BPCIA), competition in biologics markets remains scant and far from sufficient for lowering prices of biologics to the level of 80-90% price drops seen in generic drug markets. This reality is not a result of one or two cardinal reasons, but many. If lowering the price of biologics is the goal and competition is the means by which we seek to achieve that goal, then there does not seem to be a quick fix to address all of the many impediments to competition that plague biologics markets. Yet, certain changes to how the Food and Drug Administration (FDA) evaluates and approves biologics may go a long way toward the creation of meaningful competition in biologics markets. One such change would be making original biologics' manufacturing information available to follow-on manufacturers. As recognized by several commentators, access to biologics manufacturing information is key to increasing competition in biologics markets. Without access to such information, making follow-on biologics is difficult and expensive, if not outright impossible. This is expected to be especially true for the highly anticipated class of interchangeable biologics, none of which has been approved by the FDA to date. Yet, it has long been the position of the brand-name pharmaceutical industry (Industry) that biologics manufacturing information is proprietary and, thus, may not be shared. Congress has subscribed to the Industry's position, prohibiting the FDA from disclosing regulatory filings submitted by developers of original biologics, including manufacturing information, to third parties. That prohibition not only undermines competition in biologics markets, but is also wasteful, potentially unethical, and poses unnecessary risks to the health and safety of patients. This article makes the case for FDA sharing of original biologics manufacturing information with follow-on biologics developers. It is informed by the similar legal and commercial circumstances in the area of pesticides and the regulatory regime established by Congress in the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA), which is administered by the Environmental Protection Agency (EPA). The article reviews the FIFRA regime, including its upholding as constitutional by the United States Supreme Court, and then examines its applicability to the area of biologics. The article concludes with a proposal for a similar regime to be incorporated into the pathway for approval of follow-on biologics as a means of increasing competition in biologics markets.

Switching to 'best-value' generics and biosimilars saved the NHS £294m in 2018/2019, figures show

Switching to 'best-value' generics and biosimilars saved the NHS £294m in 2018/2019, figures show

A randomized double-blind parallel-group phase III study to compare the efficacy and safety of NI-071 and infliximab reference product in Japanese patients with active rheumatoid arthritis refractory to methotrexate

Objectives: This study aimed to demonstrate the equivalence of NI-071, an infliximab biosimilar (BS), and the infliximab reference product (RP) for treating Japanese patients with active rheumatoid arthritis (RA) refractory to methotrexate.Methods: In this multicenter two-period phase III study, patients were treated with BS or RP for 30 weeks (Period I) in a randomized double-blind manner and then with BS for the following 24 weeks (Period II). The efficacy and safety of BS and RP were compared.Results: The disease activity score in 28-joint count based on erythrocyte sedimentation rate or C-reactive protein and the American College of Rheumatology 20/50/70-based efficacy profiles of BS were similar to those of RP during Period I (30 weeks) including evaluations at week 14, a critical time point. BS efficacy was maintained throughout the 54-week study period. BS efficacy profile matched the RP profile until week 54 after the drug switch from RP to BS at week 30. The safety profiles of BS and RP were comparable and the long-term safety of BS was confirmed.Conclusion: BS demonstrated equivalent efficacy and safety to RP at treatment weeks 14 and 30, and long-term safety until week 54 in Japanese RA patients.

Nomenclature for biosimilars; a continuing thorny issue

Nomenclature for biosimilars; a continuing thorny issue

FDA approves Herzuma as a biosimilar to Herceptin

FDA approves Herzuma as a biosimilar to Herceptin

Substantial savings by boosting biosimilar prescribing in France

Substantial savings by boosting biosimilar prescribing in France

FDA approves Truxima as biosimilar to Rituxan for non-Hodgkin’s lymphoma

FDA approves Truxima as biosimilar to Rituxan for non-Hodgkin’s lymphoma

105P - A China-manufactured bevacizumab biosimilar, HLX04, matches bevacizumab sourced from China, USA and the European Union

105P - A China-manufactured bevacizumab biosimilar, HLX04, matches bevacizumab sourced from China, USA and the European Union

Strengths and weaknesses of the Brazilian regulation on biosimilars: A critical view of the regulatory requirements for biosimilars in Brazil.

Biological products or biopharmaceuticals are medicinal products derived from living systems and manufactured by modern biotechnological methods that differ widely from the traditional synthetic drugs. Monoclonal antibodies are the most rapidly growing type of biologic. They are much larger and more complex molecules with inherent diversity; therefore, different manufacturers cannot produce identical biological products, even with the same type of host expression system and equivalent technologies. Thus, legal follow-on biologics manufactured and marketed after patent expiration are usually referred to as biosimilars. Biosimilarity is based on a comparability exercise whereby unavoidable clinical differences are evaluated and must meet equivalence or non-inferiority criteria. Biosimilars need to comply with different regulatory requirements for market authorization in different sites. There are several other related issues that need to be defined by the national authorities, such as interchangeability, labeling and prescribing information. The Brazilian health surveillance agency follows the key principles established by the World Health Organization for the assessment of biosimilarity, although does not adopt the name ‘biosimilar’. However, the agency also made a compromise on a standalone application pathway that does not require the usual comparability exercise with the reference product, originating nonbiosimilar copies. Interchangeability and the use of nonproprietary names are not regulated, giving rise to pressures on physicians and conflicts of interest in the decision making on biosimilar use. The scope of this article is to present the Brazilian regulation on biosimilars, its strengths and weaknesses, and to discuss it in the face of regulations in the USA and Europe.

Biologics are too complicated to duplicate: should we be worried about biosimilars?

Biologics are too complicated to duplicate: should we be worried about biosimilars?

Characterization of bevacizumab by dynamic light scattering while maintaining its native structure.

Bevacizumab, is a humanized monoclonal antibody and patents on Avastin® (Bevacizumab, Roche) will expire in the US in 2019 and in Europe in 2022. Therefore, bevacizumab is a popular target for biosimilar developers. One of the most common problems in the formulation of antibody drugs is protein aggregation. Dynamic light scattering (DLS) is a well-established method for the determination of hydrodynamic dimensions, aggregates, and aggregation points of proteins. In contradistinction to other techniques that require diluted samples or specific conditions, proteins and aggregates can maintain their native structure during DLS measurements. In recent studies, bevacizumab was characterized by DLS using diluted samples. In this study, we aimed at investigating the hydrodynamic dimensions, aggregates, and aggregation onset of bevacizumab (Altuzan®, Turkey, Roche) by DLS, while maintaining its native structure. The intensity, volume, and number-based particle size distribution profiles of the test samples were evaluated and the aggregation onset of the formulation was successfully determined against increasing temperature. It is shown that the preservation of the native structure of commercial formulations in DLS measurements provides an opportunity to the characterization of commercial products and development of biosimilars.

The LILAC trial and the blooming of anticancer biosimilars

The LILAC trial and the blooming of anticancer biosimilars

FDA approves Retacrit as a biosimilar to Epogen/Procrit

FDA approves Retacrit as a biosimilar to Epogen/Procrit