Biosimilars/Research

Comparison of the markets for biosimilars and generics

Health is a typical field where the economic theory of market competition does not enjoy the basic conditions to work and the pharmaceutical market is no exception. However, as soon as a patent expires, price competition is opened up.

Patient registry data supports efficacy and safety of Inflectra

US-based injectables specialist Hospira presented data on 19 February 2015 on the use of its biosimilar version of infliximab, Inflectra, at the 10th Congress of the European Crohn’s and Colitis Organisation (ECCO).

Paying physicians to prescribe generics and biosimilars in the US

Healthcare spending on prescription medications comprises 1.6% of gross domestic product (GDP) in the US and continues to rise. Brand-name prescription medications – both small-molecule and biological drugs – are the primary driver of this growth, increasing 15% in price in 2014 alone [1].

Survey among pharmacists shows high confidence for biosimilar substitution when same generic name is used

Approximately 75% of pharmacists indicated that they would be confident or very confident in substituting an interchangeable biosimilar with the reference product if both shared the same active ingredient or non-proprietary name of the reference biological, according to a survey published in JMCP [1]. 

Equivalent safety and efficacy of nephrology subsequent entry biologics in Canada

A review of efficacy and safety data for subsequent entry biologics (SEBs) used in nephrology practice in Canada has found little clinical difference between epoetin SEBs and the reference product. But while the clinical differences are minimal, argue the authors, the financial implications of a possible dose difference between epoetin zeta and the reference product should be considered in future pharmacoeconomic studies [1].

Comparison of non-originator filgrastim with Neupogen finds no difference in neutropenia recovery periods

Results of an observational study found no difference in Biocad’s non-originator filgrastim (Leucostim) compared to Neupogen in the recovery periods for patients with chemotherapy-induced neutropenia [1].

Generics and off-patent biologicals for cancer treatment in developing countries

The understandable focus on infectious diseases, such as human immunodeficiency virus (HIV), malaria and tuberculosis (TB), has meant that an increasing burden of non-communicable diseases (NCDs), notably cancer, now needs urgent attention across developing countries [1]. Generics and biosimilars offer a lower-cost approach to treatment, but these drugs raise challenges of their own.

Positive phase III data for Amgen adalimumab biosimilar

US biopharmaceutical giant Amgen announced on 3 February 2015 positive results from its phase III clinical trial for a biosimilar version of adalimumab in patients suffering from rheumatoid arthritis.

Biosimilars compared to generics in the European market

Once a patent expires, price competition is possible since any manufacturer can copy the originator product. This circumstance justifies the place in the pharmaceutical market for generics and biosimilars, i.e. off-patent medicines to be sold at lower prices than their originators [1].

Impact of nephrology subsequent entry biologics in Canada

Subsequent entry biologics (SEBs) may soon be a reality in Canadian nephrology practice. Along with opportunities to reduce healthcare costs, these agents pose unique challenges to successful implementation. Understanding the experiences around the globe in both regulatory affairs and implementation will be a valuable guide for Canadian clinicians. This review should assist clinicians and policymakers to navigate this complex subject and to make informed decisions in the best interest of their patients [1].

No relevant difference in ADRs from biosimilars and originators

A study of adverse drug reactions reported in Italy has shown no difference between the number and type of side effects reported for biosimilars and their corresponding originators [1].

Filgrastim biosimilar has similar safety and efficacy to Neupogen

A filgrastim biosimilar (EP2006) from Sandoz, the generics division of Swiss pharma giant Novartis, has shown similar safety and efficacy compared to Amgen’s Neupogen (filgrastim) in a pivotal phase III clinical study.

Improved labelling sought for biosimilar acceptance

The terms of approval for every biosimilar and its reference product must be made clearer, argue the European Biopharmaceutical Enterprises (EBE) [1]. The development of biosimilar regulatory pathways worldwide has been led by the European Medicines Agency (EMA) [2], but EMA’s information-driven stepwise approach is only reflected in a single section of the product labelling for healthcare professionals and patients, which so far has followed a generic approach in Europe.

Regulating the safety of biosimilars

Clinical safety is critically important during the development of a biosimilar. An overview of the main aspects of safety assessment of biosimilars has been prepared to assist all those interested in this area of growing importance [1].

Biocomparable has comparable safety and efficacy to originator erythropoietin in haemodialysis patients

A study of the treatment of patients with chronic kidney disease undergoing haemodialysis with ‘biocomparable’ and originator erythropoietin in Mexico has shown comparable efficacy and safety in terms of changes in haemoglobin levels [1].

Phase I study shows darbepoetin alfa biosimilar to be well tolerated

Chong Kun Dang Pharmaceutical (CKD Pharma) announced on 18 November 2014 the successful completion of its phase I pharmacokinetics study for its biosimilar darbepoetin alfa product.

Extrapolation of indications in biosimilars: epoetin

Despite a stringent approval process, acceptance of biosimilars in the medical community continues to be low, and especially in extrapolated* indications. Members of the European Medicines Agency's (EMA) Biosimilar Medicinal Products Working Party (BMWP) address these concerns using extrapolation of indications in biosimilar epoetin as an example [1].

Non-biological complex drug concept: experiences with iron sucrose and low molecular weight heparin

When the patent of a classical small molecule drug expires, generics may be marketed if their therapeutic equivalence to the originator drug has been established. The therapeutic equivalence of a drug includes both pharmaceutical equivalence and bioequivalence and do not require formal clinical efficacy and safety studies. The demonstration of therapeutic equivalence then allows for the interchangeability of the generic and originator drug. This approach has so far only been applied to products that can be fully characterized. For more complex molecules, which are difficult to characterize, such as proteins, the demonstration of bioequivalence requires an alternative approach.

US biosimilar uptake in the light of Obamacare

A literature review by researchers at Tufts University in the US concludes that market uptake of biosimilars in the US will depend on regulatory policies, including the smoothing out of issues concerning the country’s Food and Drug Administration (FDA) regulatory pathway [1, 2]. The review comes in the light of a new approval pathway for biosimilars established as part of the US Government’s Affordable Care Act, more widely known as Obamacare.

Use of biosimilars in rheumatology

In order to issue a position statement on the use of biosimilars in rheumatic diseases, the Sociedade Portuguesa de Reumatologia (Portuguese Society of Rheumatology) carried out two systematic literature reviews: one on clinical trials and one on international position papers for biosimilars [1].

Rituximab ‘similar biologic’ shows equivalent efficacy and safety

A retrospective analysis of cancer patients who received either originator or ‘similar biologic’ rituximab chemotherapy showed comparable efficacy and safety [1].

Patient access to rituximab in emerging markets

A Pfizer-sponsored study looking at access to the oncology treatment rituximab has revealed that use of this important drug would increase across all therapy types and markets if a biosimilar was available. A rituximab biosimilar would have the greatest impact in Brazil, Mexico and Russia.

Biosimilar trastuzumab candidates in phase III development

The introduction of Herceptin (trastuzumab) revolutionalized the treatment of breast cancer. Prior to its introduction there were few treatment options available to women with human epidermal growth factor receptor 2-positive (HER2+) breast cancer.

Comparison of biosimilar filgrastim versus other G-CSF formulations after autologous stem cell transplantation

Introduction
Only limited data have been so far published about the use of biosimilar filgrastim in haematologic recovery after autologous stem cell transplantation (ASCT). Despite the limitation due to retrospective analysis performed on a limited number of patients, all these studies suggest a substantially similar efficacy of biosimilar products, when compared to originators in the febrile neutropenia prophylaxis of lymphoma and myeloma patients post-ASCT. The aim of this study was to compare the biosimilar filgrastim Zarzio with the other available formulations of granulocyte colony-stimulating factor (G-CSF) in terms of efficacy and safety [1].

Extrapolation of indications in biosimilars: filgrastim

Extrapolation* of indications for biosimilars is a contentious issue and has been met with concern by physicians. Members of the European Medicines Agency's (EMA) Biosimilar Medicinal Products Working Party (BMWP) address these concerns using extrapolation of indications in biosimilar filgrastim as an example [1].

Biosimilars: when indications can be extrapolated

Extrapolation* is already a well-established and accepted scientific and regulatory principle, according to members of the European Medicines Agency's (EMA) Biosimilar Medicinal Products Working Party (BMWP) [1].

Predicting the response of diabetes patients to biosimilar insulin

For patients with type 1 diabetes, the quality of the insulin they take is a matter of life and death. The situation is similar for patients with type 2 diabetes. The question is what will these patients think about switching from their current brand-name insulins to new biosimilar versions? The question is important right now with the imminent arrival of biosimilar insulins on the market.

Biosimilars: similar but not identical

One reason for distrust among physicians over using biosimilars in extrapolated* indications could be the fact that it is frequently cited that biosimilars are ‘similar but not identical’ compared to small molecule generics, which are often referred to as ‘identical’.

Study results show safety of switching to biosimilar infliximab

US-based Epirus Biopharmaceuticals (Epirus) announced on 23 September 2014 positive week 58 follow-up data from its global phase III study for its biosimilar infliximab (BOW015). Results of the open label phase, which was carried out in rheumatoid arthritis patients, demonstrated comparable safety and efficacy compared to the originator product (Remicade).

Extrapolation for biosimilars

Regarding extrapolation* of indications for biosimilars, the European Medicines Agency (EMA) has stated that ‘if clinical similarity can be shown in a key indication, extrapolation of efficacy and safety data to other indication(s) of the reference product may be possible’ under certain conditions [1].

Biosimilar bevacizumab similar to Avastin in preclinical assessments

Preclinical assessments have demonstrated the similarity of biologicals major Amgen’s biosimilar bevacizumab candidate (ABP 215) to Avastin [1].

Mobilization of stem cells by biosimilar Nivestim and Neupogen

Comparison of biosimilar granulocyte colony-stimulating factor (G-CSF), Nivestim and originator G-CSF, Neupogen (filgrastim), showed no statistical differences when used for the mobilization of peripheral blood stem cells in patients treated for haematological malignancies [1].

Phase III study of biosimilar adalimumab meets primary endpoint

Biologicals major Amgen announced on 8 October 2014 the first late-stage data from its biosimilars programme. Primary efficacy analysis from a phase III trial of Amgen’s adalimumab biosimilar (ABP 501) compared with Humira (adalimumab) has demonstrated ‘clinical equivalence’.

Strategy for biosimilars in China

China is one of the largest pharmaceutical markets in the world, and has seen rapid growth in the biopharmaceuticals industry in recent years.  However, it is still lacking guidance when it comes to biosimilars. Authors Li and Tuan from the Shenyang Pharmaceutical University, China, discuss how this affects biologicals companies in China [1].

Biosimilar etanercept demonstrates equivalent efficacy

A phase III trial comparing Hanwha Chemical Corporation (Hanwha)’s biosimilar etanercept, HD203, with Enbrel (etanercept) has demonstrated equivalent efficacy [1].

Adalimumab biosimilar has comparable pharmacokinetics to Humira

An adalimumab biosimilar (CHS-1420) from fledgling biotech company Coherus Biosciences (Coherus) has shown comparable pharmacokinetics in a pivotal clinical study.

The future of biosimilar use and regulation in Latin America

There is a growing uptake of biosimilars in Latin America, but this has not been accompanied by an increase in pharmacovigilance, training or regulation. To address this, an expert panel was put together to discuss the issues involved. The panel’s perspectives on the current status led to six major recommendations drawn up to enhance the safe use of biosimilars across the region [1].

ECCO survey highlights lack of confidence in biosimilar mAbs

In a presentation at the EuropaBio and the Alliance for Safe Biologic Medicines (ASBM) roundtable on naming, transparency and traceability for biosimilars [1], held on 18 March 2014 in Brussels, Belgium, Dr Alessandro Armuzzi presented results of a survey of European Crohn’s and Colitis Organisation (ECCO) members [2]. The results of the survey highlight the lack of confidence ECCO members have in biosimilars and the need for continued education.

Biosimilars in the treatment of chemotherapy-induced anaemia

A study of the use of epoetin biosimilars in the therapeutic management of anaemia secondary to chemotherapy in haematology and oncology has shown the biosimilars to be effective and well tolerated in the management of chemotherapy-induced anaemia in patients with solid tumours, lymphoma and myeloma [1].

Biosimilar trastuzumab similar to Herceptin in non-clinical study

Comparative non-clinical assessments of the proposed trastuzumab biosimilar PF-05280014 and the originator product (Herceptin) sourced in the US and in Europe showed similar structural properties, tumour cell growth inhibition properties and pharmacokinetic profiles, as well as safety profiles [1].

Phase I studies of infliximab and rituximab biosimilars demonstrate pharmacokinetic similarity

Results of phase I trials of pharma giant Pfizer’s biosimilar infliximab and rituximab candidates have demonstrated similar pharmacokinetic properties compared to the originator products [1, 2].

Biosimilar infliximab comparable to Remicade

Results from a phase III trial have demonstrated the comparability of US-based Epirus Biopharmaceuticals (Epirus) biosimilar (BOW015) to Remicade for the treatment of rheumatoid arthritis.

Can the pursuit of biosimilar interchangeability go too far?

The question of biosimilar interchangeability – whether or not a biosimilar can safely be switched with another biosimilar or with the originator product – is a thorny one. In fact, write Hans C Ebbers and Paul Chamberlain [1], striving for some of the standards suggested to certify interchangeability may not be in a patient’s best interests.

Synthon’s SYD985 outperforms Kadcyla in vitro and in vivo

Synthon announced on 2 April 2014 that its antibody-drug conjugate SYD985 had outperformed Roche’s breast cancer blockbuster Kadcyla (trastuzumab emtansine) in a head-to-head comparison.

Biosimilar epoetin shows good safety profile in post-authorization study

US-based generics manufacturer Hospira announced on 28 April 2014 positive results from a post-authorization observational safety study of its biosimilar epoetin product Retacrit/Silapo (epoetin zeta) in patients with renal anaemia [1].

Biosimilars for inflammatory bowel disease in Norway

Europe approved its first biosimilar monoclonal antibody Inflectra/Remsima (infliximab) on 10 September 2013 [1]. The biosimilar is now recommended by the Norwegian Drug Procurement Cooperation (LIS) as the first choice, which carries out the procurement for all medicines financed by public hospitals in Norway. Gastroenterologists, however, are cautious about using the biosimilar ‘until more studies of the new medicine have been completed’ [2].

Biosimilar G-CSF safe for mobilization of stem cells

A study into the use of granulocyte colony-stimulating factor (G-CSF) biosimilars for peripheral blood haematopoietic stem cell (PBSC) mobilization has found them to be equivalent to the reference G-CSF [1].

Challenges for the regulation of biosimilars

The European Medicines Agency (EMA) was the first agency to issue guidelines for the approval of biosimilars via an abbreviated registration process back in 2006. Since then the agency has developed many general and specific guidelines for biosimilars, as well as approved 18 biosimilars to date [1]. Tsiftsoglou and co-authors, however, believe that many challenges still lie ahead for this class of biologicals, some of which are discussed here [2].

Quality by design for biosimilars

A study into the use of quality by design (QbD) has demonstrated how risk management can facilitate the implementation of QbD in the early-stage product development of biosimilars [1].

Cost savings to be made by switching to Zarzio

Since the first filgrastim biosimilar was approved in 2008, there is now five years of data on which to assess the efficacy, safety and cost-effectiveness of biosimilar granulocyte colony-stimulating factors (G-CSFs). A pooled analysis of post-approval studies of one of the most common biosimilar G-CSFs, Zarzio (filgrastim), is presented by Pere Gascón and co-authors [1]. Their findings highlight significant cost savings in health authority regions that have switched from the originator G-CSF to its biosimilar Zarzio. The study overturns early concerns that cost savings would not be so great as hoped [2].

Regulatory principles for biosimilar monoclonal antibodies

It is sometimes argued that there is less clinical evidence for biosimilars. However, Tsiftsoglou and co-authors pointed out that European Medicines Agency (EMA) guidelines for biosimilars are not primarily driven by feasibility considerations or to make it as easy as possible, but to add to the totality of evidence. And it is this that finally drives the regulatory acceptance of a biosimilar [1].

Are biosimilars worth it?

Will off-patent biological medicines offer the same cost savings as those seen with off-patent non-biological (chemically derived) medicines? A group of health economists based in Brussels, Belgium, have begun to address the question in light of increasing numbers of biological medicines going off patent and the new phenomenon of biosimilar competition [1].

Protein aggregation and the generation of immune responses

During a presentation given by Ms Melody Sauerborn (TNO Triskelion, The Netherlands) at an international conference on biowaivers and biosimilars, held in the US in September 2012, the immunological aspects of formation of anti-drug antibodies against aggregated protein drugs were discussed [1].

How safe is Zarzio after five years’ clinical experience?

The first filgrastim biosimilar was approved in Europe in 2008, prompting Dr Pere Gascón and co-authors to review the evidence relating to the efficacy and safety of biosimilar Zarzio (filgrastim) and Filgrastim Hexal (filgrastim) since that time. The authors report a pooled analysis of post-approval studies of Zarzio (Sandoz) used for the prevention of neutropenia in patients with cancer who are undergoing cytotoxic chemotherapy [1].

Biosimilar epoetin-κ equivalent to epoetin-β

In 1989, the first recombinant erythropoietin (rEPO) preparation, epoetin-α, was approved by the US Food and Drug Administration for the treatment of anaemia associated with kidney disease. Since then, several clinically approved rEPO preparations, such as epoetin-β, epoetin-δ and the epoetin-α derivative, darbepoietin-α, have been commercially produced. Since the expiration of patent protection, a number of biosimilars have also been approved on the world market.

Inflammatory arthritis: auditioning for the role of biosimilar

Targeted biological therapies have proven themselves highly effective in the treatment of inflammatory joint diseases, but their benefits are restricted by cost. Biosimilars of these therapies would offer affordable alternatives, but establishing biosimilarity presents many challenges, write Professors Jonathan Kay and Josef Smolen [1].

Guiding principles for biosimilars development

In contrast to chemically synthesized small-molecule drugs, biologicals have complex structures of high molecular weight. Therefore, even small changes in the production processes may lead to differences in the final product. The manufacturers of the originator product are not required to disclose their manufacturing process after the patent expiry. This gap in knowledge increases the probability of introducing changes in the manufacturing process of biosimilars, making producing an identical copy of a biological virtually impossible. Indeed, even different batches of the same originator biological may show a certain level of heterogeneity.

Use of formularies could increase use of biosimilars

Whether or not the US Food and Drug Administration (FDA) permits automatic substitution of biosimilars, healthcare systems can still consider using formularies as a way to increase the use of more affordable biosimilars [1].

The case for improving biosimilar regulatory frameworks worldwide

In developing countries, where the cost benefits of biosimilar drugs would have the greatest impact, the financial investment needed to develop biosimilars renders them inaccessible. The situation requires increased input from international evaluation frameworks, such as those of the World Health Organization (WHO); write Barbara Milani and Sara Gaspani of Médecins Sans Frontières, Geneva, Switzerland [1].

Improving access to HCV treatment in developing countries

Hepatitis C virus (HCV) infection affects 150–180 million people worldwide each year, killing an estimated 350,000. The considerable cost of treatment – US$ 10,000–US$20,000 per patient for a 48-week course – presents an insurmountable barrier in developing countries, where the disease burden is greatest. Barbara Milani and Sara Gaspani of Médecins Sans Frontières, Geneva, Switzerland, have collected information on biosimilars and other alternatives to the current recommended treatment, pegylated interferon alpha (in combination with ribavirin) [1]. With these findings, they hope to accelerate the search for feasible, accessible alternatives to current therapies.

Bioanalytical challenges in the development of biosimilars

Some of the topics presented at an international conference on biowaivers and biosimilars, held in the US in September 2012, were applicable to large-molecule bioanalytical methods. These included assay format, glycosylation and immunogenicity, and how differences in these components can impact the evaluation of biosimilars and their subsequent approval.

Immunogenicity testing in biosimilars

During a presentation given by Dr Kelly Colletti (Laboratory Sciences, USA) at an international conference on biowaivers and biosimilars, held in the US in September 2012, it was discussed whether one or two assays should be employed in order to measure anti-drug antibodies to both the biosimilar and reference biological in a comparative manner [1].

Analysis of carbohydrate containing biosimilars

During a presentation given by Dr Azadi Parastoo, University of Georgia, GA, USA, at the international conference on biowaivers and biosimilars, held in the US in September 2012, the types of analytical techniques that can be utilized in order to characterize differences in glycosylation for analysis of biosimilars were discussed [1].

Establishing mAb biosimilarity before reaching the clinic

Confirming the biosimilarity of monoclonal antibodies (mAbs) is fraught with challenges beyond those faced by currently approved biosimilars, warn Ebbers and co-authors at Utrecht University, The Netherlands [1]. The threat of unexpected immunogenicity has been well reported, but the problems do not start there. The first steps towards establishing the biosimilarity of an anticancer mAb, the preclinical stage, presents challenges of its own.

Challenges and opportunities for anticancer mAbs

Several best-selling monocloncal antibodies (mAbs) are due to lose patent protection; presenting regulatory authorities with a complex set of challenges as they prepare for the arrival of novel biosimilars, note Ebbers and co-authors at Utrecht University, The Netherlands [1].

Phase III QoL assessments show comparability of biosimilar infliximab

The results of phase III quality of life (QoL) assessments of a candidate biosimilar infliximab (CT-P13) have shown the comparability of the biosimilar (CT-P13) and its reference product, Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab).

Phase I study shows equivalence of biosimilar rituximab and MabThera

The results of a randomized, controlled, multicentre, two-arm, parallel-group, double-blind study of CT-P10 (rituximab) in patients with rheumatoid arthritis has shown the equivalence, with respect to pharmacokinetics, efficacy and safety, of the biosimilar (CT-P10) and its reference product, Roche’s rheumatoid arthritis blockbuster MabThera/Rituxan (rituximab).

Non-clinical and phase I clinical assessments show similarity of biosimilar rituximab

The results of non-clinical and phase I clinical assessments of a candidate biosimilar rituximab (PF-05280586) have shown similarity, with respect to in vivo, functional characteristics and pharmacokinetic and pharmacodynamic properties, of the biosimilar (PF-05280586) and its reference product, Roche’s rheumatoid arthritis blockbuster MabThera/Rituxan (rituximab).

Open-label studies show similarity of biosimilar infliximab and Remicade

The results of two open-label extension studies of Inflectra (CT-P13; infliximab), one in patients with rheumatoid arthritis, the other in patients with ankylosing spondylitis, have confirmed the similarity, with respect to efficacy and safety, of the biosimilar infliximab and its reference product, Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab).

Etanercept biosimilar has comparable pharmacokinetics to Enbrel

An etanercept biosimilar (CHS-0214) from fledgling biotech company Coherus Biosciences (Coherus) has shown comparable pharmacokinetics in a pivotal clinical study.

Use of similar biotherapeutic products to treat rheumatoid arthritis in Latin America

Latin America has a significantly lower gross domestic product (GDP) compared to Canada, Europe and the US. Despite this fact, the cost of biologicals is in general very similar to countries with higher GDP, causing problems for patients to gain access to these medications. This problem could possibly be solved by the introduction of lower-cost biosimilars to the region.

Clinical trials for follow-on biological products in Brazil

Unlike for generic drugs, authorizing biosimilars without conducting quality clinical trials represents a real threat to patients, according to Professor Valderílio Feijó Azevedo, Professor of Rheumatology at the Universidade Federal do Paraná in Brazil [1].

Extrapolation of biosimilar infliximab indications to inflammatory bowel disease

Gastroenterologists are wary of using biosimilars of infliximab in the treatment of inflammatory bowel disease. This fact is being evidenced by the publication of position statements from various professional groups.

The future of nanomedicines – nanosimilars

First there were generics, then came biosimilars and soon the European Medicines Agency (EMA) is anticipating the first nanosimilars, or similar versions of originator nanomedicines.

Regulation of similar biotherapeutic products in Latin America

Regulation of similar biotherapeutic products (SBPs) in Latin America varies widely among different countries and, although many countries have yet to introduce guidance for biosimilars, the region is moving towards increasing standards of regulation for these products [1, 2].

Positive phase III data for Epirus infliximab biosimilar

US-based Epirus Biopharmaceuticals (Epirus) announced on 28 August 2013 that its biosimilar infliximab candidate had demonstrated ‘clinical comparability’ to Remicade as measured by the ACR20 response in severe rheumatoid arthritis patients.

Assessment of efficacy and safety of biosimilars in rheumatology

During the last decade, the availability of biological therapies has revolutionized the treatment of rheumatoid arthritis. Biologicals, unlike small-molecule chemical drugs, are extremely complex molecules, making producing biosimilars far from a simple process.

Cost savings from use of biosimilars in rheumatology

The treatment of rheumatoid arthritis provides a clear argument in favour of developing biosimilars and the need to collect sufficient pharmacological data to validate their bioequivalence and interchangeability.

Infliximab biosimilar comparable to Remicade

South Korean biotechnology company Celltrion presented results of its extended trials for its biosimilar infliximab candidate Remsima (CT-P13) at the European League Against Rheumatism (EULAR) 2013 Conference, which was held in Madrid, Spain on 12–15 June 2013.

Erythropoietin biosimilars in bone marrow transplantation and stem cell donation

Combination therapy with granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) has been used with the aim of accelerating the recovery of red blood cells following autologous bone marrow transplantation [1]. Previous studies have shown, however, that this practice has no significant effect on erythroid recovery and transfusional requirements.

Robust data for biosimilar trastuzumab programmes presented

Celltrion and Pfizer have presented robust data from their respective biosimilar trastuzumab programmes at the ASCO (American Society of Clinical Oncology) 2013 Annual Meeting held on 31 May to 4 June 2013.

Use of G-CSF biosimilars for reduction of fever

The American Society of Hematology, the British Society of Haematology, the European Society of Hematology and the European Group of Bone Marrow Transplantation all recommend the use of granulocyte colony-stimulating factor (G-CSF) after transplant in order to reduce the time to neutrophil recovery and the number of days with fever.

Positive post-marketing data for biosimilar epoetin

Injectable generics specialist, Hospira, presented results from a post-marketing study of the company’s European biosimilar epoetin (Retacrit) on 3 June 2013 at the 48th Annual Meeting of the American Society of Clinical Oncology (ASCO) held in Chicago, USA.

Use of G-CSF biosimilars for stem cell mobilization in autologous transplantation

The first biosimilar granulocyte colony-stimulating factor (G-CSF) was licensed by EMA in 2008, and there are currently six biosimilar G-CSF products licensed for use in the EU [1]. All of these biosimilars are also approved for haematopoietic stem cell transplantation.

Biopharmaceutical products in Iran

Iran will become a leader in biotechnology products (especially copied biopharmaceuticals [1]) in Asia over the next three years, according to a review by Mahboudi et al. [2].

Use of G-CSF biosimilars for stem cell mobilization in healthy donors

Granulocyte colony-stimulating factor (G-CSF) can be used to mobilize peripheral blood stem cells (PBSCs) in healthy donors. Over the last 10 years, the procedure has become the preferred option for donors compared to the donation of bone marrow.

Saving money in the European healthcare system with biosimilars

Biotechnology-derived medicines are increasingly popular for treating a range of conditions from cancer to autoimmunity, and yet they are among the most expensive healthcare products owing to their manufacture using live cell cultures. As healthcare providers become increasingly concerned about rising costs, interest is turning to the idea of substituting reference biological drugs with cheaper but similar biological products, or biosimilars, after patents expire on reference products. The use of biosimilars has the potential to reduce healthcare expenditure, particularly for long-term treatments, which incur high annual treatment costs.

Development of biosimilars for rheumatology

In 2012, worldwide sales for the top three selling tumour necrosis factor (TNF) inhibitors reached US$20 billion. These biological treatments for arthritis are costing patients between US$10,000–US$30,000 per year making the need for lower cost biosimilars clear [1].

Research on clinical trial issues for biosimilars

Period: September to December 2012 

In order to demonstrate comparability between a biosimilar and its reference product, EMA recommends that the clinical trial should make it possible to detect a difference between the biosimilar and reference product. In most cases, this means that a two-arm clinical trial design (reference biological and biosimilar) in a small group of homogenous patients may be used. If the two arms of the trial produce similar results, then the biosimilar can be approved.

Quality, similarity and safety of biosimilars

An abbreviated pathway for the approval of biosimilars was implemented in the EU in 2005. Despite biosimilars being available in Europe for more than seven years, physicians still have concerns about the use of biosimilars. Members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) highlight what physicians need to know to make informed and appropriate treatment choices for their patients [1].

Phase I/IIb trial of CT-P6 shows comparability to trastuzumab

Results of a phase I/IIb trial for South Korean biotechnology company Celltrion’s biosimilar candidate CT‑P6 were presented at the 13th St Gallen International Breast Cancer Conference held in St Gallen, Switzerland, on 13–16 March 2013. The results demonstrated the comparable pharmacokinetics and safety of CT-P6 to the reference drug.

Research on biosimilars in anaemia and diabetes

Period: September to December 2012 

The use of biological medicines has been life-changing for many patients suffering with anaemia and diabetes. With the expiration of patents on these biologicals the possibility of patients gaining access to lower cost biosimilar alternatives to these extremely effective, but costly, medicines becomes a real possibility.

Biosimilars in rheumatology

Patents on key biological medicines used in rheumatology will expire soon. The European Medicines Agency’s (EMA’s) finalized guidelines on biosimilar monoclonal antibodies (mAbs) came into effect on 1 December 2012. Both of these facts mean that rheumatologists can expect to be exposed to biosimilars of the medicines they routinely use in the near future.

How are biosimilars special

Despite biosimilars being around in the EU since 2006 physicians are still often reluctant to prescribe them. Members and experts of the Working Party on Similar Biologic Medicinal Products of the European Medicines Agency (EMA) highlight what physicians need to know to make informed and appropriate treatment choices for their patients [1].

Quality attribute changes for rituximab

Last updated: 4 April 2013 

Sandoz researchers found quality changes in commercially available rituximab (Rituxan/Mabthera) over a period of time. Since the drug remained on the market with an unchanged label, this would indicate that the changes were accepted by the health authorities.

Research on biosimilars in rheumatology

Period: September to December 2012 

Over the past decade, the availability of targeted biological therapies has revolutionized the treatment of rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis. However, the significant cost of these biologicals is often prohibitive and limits universal access to these effective therapeutic agents. Whereas generic drug equivalents are commercially available for many small-molecule medications, such lower cost alternatives to targeted biological therapies are not yet available in the US or the EU.  The first biological therapeutics in rheumatology is now approaching patent expiration and biosimilars are now in randomized controlled trials. This means that cheaper biosimilars for the treatment of rheumatic diseases are likely to enter the market in the near future, increasing patient access to these life-changing treatments.

Prospects for producing follow-on biological products in Brazil

New research shows the need for local production of biologicals in Brazil in order to offset the increasing medicines budget and reduce the trade deficit when it comes to drugs [1].

MS patient dies from immunogenicity to biological drug

A Swedish woman diagnosed with multiple sclerosis (MS) appears to have died after developing unwanted immunogenicity toward the biological drug Tysabri (natalizumab), according to a report in the journal Neurology [1].

Medicines spending in Brazil

The Brazilian pharmaceutical market is the third largest in the Americas region, behind the US and Canada; it ranks first in the Latin American region. Pharmaceutical demand will continue to rise, fuelled by increasing disposable income. Despite this positive outlook, the trade deficit in Brazil grew from US$700 million at the end of the 1980s to a cumulative US$7.13 billion in 2008. In 2008 alone, Brazil imported US$1.4 billion in vaccines, serum and blood products, while exporting US$37 million in medicinal products with low added value [1].

Biologicals boom

Researchers predict that the present list of top 10 blockbuster drugs will change dramatically by 2014. The predictions are that by 2014 biological drugs will topple the present market leaders Pfizer’s Lipitor (atorvastatin) and Sanofi’s Plavix (clopidogrel), both of which are small molecule chemical entities [1].

Mobilization of stem cells in healthy donors by G-CSF biosimilars shows comparable efficacy and safety to Neupogen

Originator human recombinant granulocyte colony-stimulating factor (G-CSF) filgrastim has been widely used for the mobilization of CD34⁺ stem cells in healthy donors. However, there is limited experience with the use of biosimilar G-CSF for the mobilization of peripheral blood stem cells (PBSCs), especially in healthy donors. A recent study by Professor Schmitt and co-authors has addressed this issue and found that biosimilar G-CSF showed comparable efficacy and safety with reference G-CSF (Neupogen) when used for the mobilization of CD34⁺ stem cells, as well as CD3⁺ T-cells and nucleated cells, in healthy donors [1].

Overview of research on G-CSF biosimilars in 2012

Period: January to August 2012 

A life-threatening complication for patients undergoing chemotherapy is febrile neutropenia, involving a loss of neutrophils (white blood cells) and fever [1]. Granulocyte colony-stimulating factors (G-CSFs) are growth factors, which stimulate the bone marrow to produce white blood cells and restore neutrophil production. In oncology and haematology, G-CSF is used with certain cancer patients to accelerate recovery from neutropenia after chemotherapy, allowing higher-intensity treatment regimens.

Positive phase I data for infliximab biosimilar

US-based Epirus Biopharmaceuticals (Epirus) announced on 4 January 2013 that its biosimilar infliximab candidate had ‘achieved bioequivalence’ to Remicade (infliximab) in a single dose comparator trial.

Overview of research on analytical techniques in the manufacturing of biosimilars in 2012

Period: January to August 2012 

Biologicals are large, complex and heterogeneous proteins with variable molecular weights, typically ranging from 18,000 to 45,000 Da. The active substance of a biological is a collection of large protein isoforms and not a single molecular entity. This fact makes manufacturing of biosimilars much more of a challenge than when producing traditional small molecule generics. It also makes it highly unlikely that the active substances between two products are identical and makes it extremely difficult to establish biopharmaceutical equivalence using analytical techniques.

Biosimilar monoclonal antibodies on the horizon in Europe

European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use adopted the final guideline on biosimilar monoclonal antibody (mAb) and it came into effect in December 2012. The agency is also currently reviewing two marketing authorization applications (MAAs) for the biosimilar mAb infliximab.

Significance of locally produced biosimilars in Iran

Biopharmaceuticals, drugs produced by live cell culture, have a fast growing market for the treatment of a range of conditions. Despite their clinical importance, however, their cost could impose an increasing burden on either national healthcare systems or patients’ out-of-pocket expenses. The potential for reducing the costs of biopharmaceuticals is therefore attracting the attention of policymakers in the health sector.

History of biosimilar monoclonal antibodies regulation in EU

Monoclonal antibodies (mAbs) are high molecular weight proteins (~150 kDa), with highly complex secondary and tertiary structures, subject to post-translational modifications, such as glycosylation.

Overview of research on manufacturing statistics and innovations of biosimilars in 2012

Period: January to August 2012 

Manufacturing of biosimilars is much more challenging than producing traditional small molecule generics. Reasons for this include, in the first place, the huge costs associated with manufacturing of biosimilars, along with the fact that the risk of failure for biosimilars is significantly higher than that for small molecule generics. Secondly, biosimilars are larger and more complex molecules to manufacture. Finally, minor changes in the manufacturing process can cause significant changes in efficacy or immunogenicity.

Comparison of EPARs for G-CSF biosimilars approved in Europe

EMA approved its first biosimilar granulocyte colony-stimulating factor (G-CSF, filgrastim) for use in Europe back in 2008, since then, several biosimilar G-CSFs have been approved, including Biograstim, Filgrastim ratiopharm, Ratiograstim, Tevagrastim, Filgrastim Hexal, Zarzio and Nivestim. All biosimilar G-CSFs were approved using Amgen’s Neupogen as the reference product. Filgrastim ratiopharm was withdrawn on 20 April 2011.

Overview of research on regulatory issues surrounding biosimilars in 2012

Period: January to August 2012 

In the area of regulation of biosimilars Europe has by far the best-established framework for approval and EMA has already issued both general and product specific guidelines for biosimilar applications to the EU [1]. The first biosimilar was approved in the EU in 2006 for Omnitrope (somatropin). There are now 14 biosimilars approved for use in Europe for three reference products: erythropoietin, granulocyte-colony stimulating factor and somatropin [2].

Overview of research on US regulatory issues surrounding biosimilars in 2012

Period: January to August 2012 

The US is somewhat behind Europe in the biosimilars race, but has issued draft guidance and is expected to have a practical biosimilar approval pathway in place in the near future.

Dialogue needed to build confidence in biosimilars

Concerns about the safety and efficacy of biosimilars have led many healthcare professionals to become reluctant to prescribe these products for their patients [1]. According to a commentary by Dr Hans C Ebbers and co-authors, these concerns could be addressed through more engagements taking place between regulatory authorities and the medical community over the drafting of regulatory guidelines [2]. This would result in greater confidence in the regulatory process and trust in the products that gain approval.

Positive results from phase III study with biosimilar human insulin

One of Asia’s leading biotechnology companies, Biocon, announced on 31 October 2012 positive results from its global phase III study for its recombinant human insulin (Insugen). The study, which was carried out in type 1 diabetes mellitus (T1DM) patients, demonstrated comparable safety and efficacy compared to the originator product.

Sandoz starts phase III US trial for biosimilar epoetin alfa

Sandoz, the generic drug division of Swiss drug giant Novartis, announced on 25 October 2012 that it had started patient enrolment in a phase III clinical trial in the US for biosimilar epoetin alfa (Amgen/Johnson & Johnson’s Epogen/Procrit).

Pfizer carrying out biosimilar trastuzumab trial in US

Pharma giant Pfizer is carrying out a phase I trial in the US for a biosimilar version of trastuzumab.

Overview of research on biosimilarity/comparability and interchangeability of biosimilars 2012

Period: January to August 2012 

After the patent on a biological medicine expires ‘similar’ versions of the originator biological can be produced. These biosimilars or ‘similar biological medicinal products’ are similar (but not identical) in terms of quality, safety and efficacy to an authorised reference biological medicine.

Boehringer Ingelheim completes biosimilar adalimumab trial

Biopharmaceutical specialist Boehringer Ingelheim Pharmaceuticals (Boehringer Ingelheim) has completed its phase I trial for a biosimilar version of adalimumab.

Overview of research on safety and immunogenicity of biosimilars in 2012

Period: January to August 2012 

Biosimilars or ‘biosimilar medicinal products’ are medicinal products that are similar (but not identical) in terms of quality, safety and efficacy to an authorised biological reference medicine. Manufacturing of biologicals is complex, and the quality of the resulting biological is dependent on careful control of manufacturing processes and conditions. Unlike traditional small molecule (chemical) drugs, the development of biologicals is different and variable with respect to the manufacturing process and environmental factors, such as light and temperature. The complexity and heterogeneity of the molecular structure, complicated manufacturing processes, different analytical methods and possibility of immunogenicity reactions make quantitative evaluation of biosimilars a challenge to both the scientific community and regulatory agencies.

Boehringer Ingelheim starts biosimilar rituximab trial

Germany-based Boehringer Ingelheim Pharmaceuticals (Boehringer Ingelheim) is starting a Phase III trial for a biosimilar version of rituximab.

Biosimilar comparability debate continues

Authors Schellekens and Moors comment on the response from EMA’s Biosimilar Medicinal Products Working Party to questions that they raised regarding EMA’s comprehensive biosimilar regulatory pathway [1]. While the authors express their appreciation of the openness of EMA in the way it has pioneered the biosimilars pathway in Europe, they still argue that EMA has failed to show the scientific need for biosimilar comparability [2].

EMA responds to questions over biosimilar comparability

EMA has responded to questions regarding its comprehensive biosimilar regulatory pathway. The pathway, which includes the need for new clinical trials and comparability studies that demonstrate quality, efficacy, and safety, has been accused of proving to be a barrier for the development of clinically superior compounds [1].

Patients and biosimilar interchangeability

Biopharmaceuticals or biologicals are complex medicines produced by living cells. Copies of approved biologicals have been introduced recently. Because of their intrinsic complexity such copies are similar but not identical to the reference medicine and are therefore called ‘biosimilars’. Approval of biosimilars requires a full quality analysis including a detailed comparison to the reference whereas non-clinical and clinical evaluations are less extensive.

Investigating G-CSF biosimilars approved in Europe

A life-threatening complication for patients undergoing chemotherapy is febrile neutropenia, involving a loss of neutrophils (white blood cells) and fever. Granulocyte colony-stimulating factors (G-CSFs) are growth factors which are used to restore neutrophil production.

Is pegfilgrastim superior to filgrastim for the treatment of febrile neutropenia?

A study to compare the cost-efficiency of three different recombinant granulocyte colony-stimulating factors (G-CSFs) for the treatment of chemotherapy-induced febrile neutropenia assumes that they are of comparable efficacy. But how solid is the evidence for this assumption? A study by Professor Matti Aapro and co-authors explores the available evidence regarding efficacy for the three G-CSFs, filgrastim (Neupogen, Amgen), pegfilgrastim (Neulasta, Amgen) and a filgrastim biosimilar (Zarzio, Sandoz/Novartis) and concludes that evidence behind previous claims of superiority for pegfilgrastim is ‘similar’ and ‘open to question’ [1]. Thus, originator and biosimilar filgrastim appear to be holding ground in the efficacy stakes.

Immunogenicity of biologicals

This article discusses the issue of immunogenicity with respect to originator biologicals and biosimilars [1].

Pricing of biosimilars

For small molecule generics, reductions in price of around 80% have been observed after the first six months to a year of generics entry to the market in countries such as Germany, UK and the US [1, 2]. Biosimilars, however, are an entirely different entity.

Factors affecting market access of biosimilars

Growth in the use of biosimilars is being driven by the need to reduce healthcare costs, patent expiries on blockbuster originator biologicals and better-defined regulatory pathways.

Testing for unwanted immunogenicity from biologicals

Immunogenicity caused by biologicals, both originator and biosimilar, is an important issue that was raised by Dr Wadhwa from the National Institute for Biological Standards and Control [1].

Positive results from phase I study with biosimilar insulin glargine

Leading biotech company Biocon announced on 25 July 2012 positive results from a phase I comparative study conducted in Germany of its biosimilar insulin glargine in type 1 diabetes mellitus (T1DM) patients.

Biosimilar infliximab equivalence proven in phase III trial

Results from a phase III trial of biosimilar infliximab have proven the equivalence of South Korean biotechnology company Celltrion’s biosimilar (CT-P13) and the reference product – Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab) in terms of safety and efficacy in patients with active rheumatoid arthritis [1].

Small molecule versus biological drugs

Biological drugs are large and complex, often consisting of heterogeneous mixtures. They are generally made in genetically engineered cells that impose their own variabilities–in post-translation modifications such as glycosylation–on the processes used to make such drugs.

Phase I trial of biosimilar infliximab proves biosimilarity

Results from a phase I trial of biosimilar infliximab have proven the equivalence of South Korean biotechnology company Celltrion’s biosimilar (CT-P13) and the reference product – Johnson & Johnson’s rheumatoid arthritis blockbuster Remicade (infliximab) in terms of pharmacokinetic parameters, as well as in safety and efficacy in patients with active ankylosing spondylitis [1].

Prescriber caution is likely over biosimilars

The experience with generic medicines is a sign that prescribers are likely to be cautious, and in some cases concerned, about the use of biosimilars as alternatives to brand-name drugs.

Biosimilar filgrastim provides cost savings for treating febrile neutropenia

Professor Aapro and co-authors have performed a cost-efficiency analysis for the three most common granulocyte colony-stimulating factors (G-CSF) products used to treat febrile neutropenia: filgrastim (Neupogen, Amgen) and its biosimilar (Zarzio, Sandoz/Novartis) and the pegylated form of filgrastim, pegfilgrastim (Neulasta, Amgen) [1]. Filgrastim is more cost-efficient than pegfilgrastim for up to 12 days of treatment: beyond 12 days, pegfilgrastim becomes the most cost-efficient of the two. But above all, biosimilar filgrastim is the most cost saving compared to both originator filgrastim and pegfilgrastim.

Bioavailability comparison of brand-name and generic acetylcysteine in China

A study comparing brand-name and generic acetylcysteine in China by Liu et al has shown that the generics test formulation was bioequivalent to the originator drug [1].

Oncologists urged to embrace biosimilars to help control spiraling costs of cancer care

Oncologists have been urged to embrace biosimilar drug substitution to help control the spiraling costs of cancer care. However, they have been warned that the optimal realisation of such a programme requires successful educational initiatives and the development of effective working partnerships with pharmacists and patients [1].

The controversies surrounding biosimilars

It is well known that the introduction of similar biological medicinal products, or biosimilars, has caused not a little controversy in the medical world. The aim of healthcare providers/payers, either healthcare authorities or insurance companies, is to reduce the healthcare budget has risen in recent years through the introduction of expensive companion diagnostics, devices, and drugs. At the present moment this can only be achieved in two general ways: either the availability of therapies must be restricted from the patients who would benefit from them, or otherwise the costs of the procedures and drugs must be reduced to within affordable limits so that the majority of patients can benefit from them.

Study of biosimilar enoxaparins in Brazil

Analysis of biosimilar enoxaparins available for clinical use in Brazil by the Laboratório de Tecido Conjuntivo in Brazil have shown that the biosimilar preparations of enoxaprain are similar to the originator drug [1].

Biosimilars dilemma over reference products

Global manufacturers of biosimilars have a dilemma on their hands concerning reference products. What to do to reduce the burden of data required in different countries and regions of the world to get their biosimilars onto the market?

Current and future issues surrounding biosimilars

Biological medicines are already becoming an increasingly important part of health care. With patent expiries on originator biological products, biosimilars are also increasingly become a part of this future [1]. In fact, by 2020 twelve of the top-selling biologicals will have lost patent protection, opening up an estimated US$24 billion in EU sales and US$30 billion in US sales [2].

Reimbursement of biosimilars

The evidence required to obtain marketing authorisation for a biosimilar by the regulatory authority is not always the same as that required by the reimbursement authority [1]. This can cause problems for biosimilars manufacturers when planning clinical trials in order to obtain both marketing and reimbursement approval.

Comparability studies and substitution of biosimilars

In order to demonstrate similarity between the biosimilar and the biological reference product, both products must be compared to satisfy quality, safety and efficacy requirements [1].

Biosimilars: demonstrating ‘similarity’

Most biological drugs are mixtures of closely related compounds, some of which are probably more active than others. Today, the state-of-the-art manufacturing struggles to deliver material that is similar to the prior batch from the same facility and team [1]. Identical is currently not possible, therefore ‘similar’ is the route that authorities in Europe and the US are going down.

Registration of biosimilars in Europe and the US

Europe is way ahead of the US in terms of biosimilars regulation. A legal framework for approving biosimilars in the EU was established in 2003 and guidelines for an abbreviated registration process were issued in 2006 [1].

EMA risk management plans may increase prescriber confidence in biosimilars

In the absence of observational (phase IV) data, EMA’s stipulation that all marketing applications for new generation biosimilars contain individual risk management plans may help to increase prescriber confidence in the compounds [1].

The cost-effectiveness of biosimilars

The biotechnology market is growing rapidly, driven by the imminent patent expiry of several major biologicals and enabled by the establishment of regulatory frameworks. The key driver for the biosimilars market is likely to be cost containment pressures in healthcare systems in the context of aging populations and of the current financial and economic crisis [1]. Because the medicines involved are so expensive, even a modest price reduction in percentage terms generates savings in the billions of euros over the EU as a whole [2].

Physician perceptions of generics substitution

How do physicians perceive generics substitution? Many patients do not communicate with their physicians regarding out-of-pocket expenses or medication choices. Therefore, understanding physicians’ perceptions about the quality and efficacy of generics could help to identify potential barriers to increasing the use of generic drugs [1].

Biosimilar epoetins: how similar are they?

As the patent expiry dates of the original erythropoietins drew near, much concern was expressed in 2004 about possible biosimilar competitors. Product quality, safety and efficacy of biopharmaceuticals are highly dependent on the processes of production, purification and formulation. How have these genuine concerns been answered by the EMA in granting marketing approval, and have any other problems come to light?

Relative effectiveness and cost minimisation for biosimilars

The second of two articles on the use of economic evaluations to guide the use of expensive treatment.

Economic evaluation of biosimilars

Biological drugs represent a fast-growing segment of the pharmaceutical market. They make up 32% of drugs in the development pipeline and 7.5% of marketed medicines and account for around 10% of pharmaceutical expenditure [1].

India at the biotech crossroads

‘Indian biotech is at a crossroads. It must not only address the significant health needs of its domestic population, but also position itself to take advantage of the often more profitable global marketplace.’ [1]

Interchangeability (switching and alternating) of biosimilars

The Biologics Price Competition and Innovation (BPCI) Act of 2009 established an abbreviated Biologic License Application (aBLA) pathway for the approval of biosimilars in the US. This act also established the principles of interchangeability (along with switching and alternating) with the reference product. However, the concept of biosimilarity and interchangeability for biosimilars is very different from that of bioequivalence and drug interchangeability for generics [1].

Quantitative evaluation of bioequivalence

Generics
For approval of small molecule generics, FDA requires that evidence of average bioequivalence in drug absorption in terms of pharmacokinetic (PK) parameters be provided through the conduct of bioequivalence studies. This may be done using the area under the blood and/or plasma concentration-time curve and peak concentration (Cmax) [1].

US cancer researcher calls for additional biosimilar trials

One of the leading cancer researchers in the US has called for biosimilars manufacturers to undertake additional research. In an interview with The ASCO Post, Professor Mark Pegram, MD, Professor of Medicine and Associate Director for Clinical Research, Sylvester Comprehensive Cancer Center at the University of Miami Health System, Florida, USA, said, ‘Oncologists will be concerned about the safety of biosimilars. They will want to ensure that the chemistry, manufacturing, and composition are on par with the labelled product.’

US biosimilars: many barriers to overcome

EMA has been successful in devising a system for authorising the marketing of biosimilar products and 14 biosimilars are currently on the market in the major countries of the EU [1]. Generally, biosimilars are priced about 30% less than the originator product. This seems to be sufficient to gain significant (~ 30%) market share in a year or two though it keeps biosimilars very expensive. This is in dramatic contrast to the situation in America. In 2010 the ‘biosimilars statute’ (BLA) eventually came into force as the result of the Patient Protection and Affordable Care Act. The proposed rule involves two particularly onerous requirements that the EU process avoids.

The first is the question of degree of similarity.

Can biosimilar manufacturers learn from generic substitution issues

The substitution of generic prescription medicines for branded medicines is practiced in most Westernised countries, mainly because of its clear economic benefits. Patient experiences of generic substitution are mixed however, with many patients left confused or suspicious [1]. Given that a number of second-generation biosimilar compounds are expected to be approved within the next few years, and that biosimilar manufacturing costs are much higher than those of a simple generic, it is crucial for biosimilar manufacturers to avoid the uncertainty and mistrust that often accompanies generic substitution. Several recommendations have been made to help ensure that substitution pathways are streamlined and successful [1] but can any of these recommendations be applied to biosimilars?

US biosimilars: a report on FDA progress

This article reviews the steps being taken by FDA to implement the Biologics Price Competition and Innovation (BPCI) Act of 2009, enshrined in law in 2010 as the ‘biosimilars statute’.

Development of biosimilars is not an easy matter

By 2020 biological products with sales of around US$23 billion in the EU and US$29 billion in the US will be exposed to biosimilar competition [1]. As more and more biologicals lose their patent protection, it is no wonder that Big Pharma, the biotechnology industry and generics manufacturers, as well as regulatory agencies, are becoming increasingly interested in biosimilars [2].

US biosimilars law may prove a barrier to entry for biosimilars

One of the main barriers to biosimilar entry in the US is the US biosimilars law [1]. While some have questioned whether the biosimilars pathway in the US will ever be used [2, 3], others believe that, although flawed, the US biosimilars pathway is likely to become a functioning legal pathway [4].

Brand-name statins costing healthcare system US$6.7 billion

Researchers at Mount Sinai School of Medicine, New York, USA, found that physicians prescribing unnecessary treatments or diagnostic tests, spanning a broad range of clinical conditions, costs the US healthcare system an extra US$6.7 billion annually. The findings, published in Archives of Internal Medicine, attributed prescribing of brand-name statins instead of generic statins as accounting for most of the excess cost [1].