Biosimilar Approval Pathway Research Articles

HPR13 Medicare Part B Spending on Biologics Due to Inadequate Biosimilar Uptake

Biologics represent a rapidly growing portion of Medicare drug spending. To lower prices, the United States (US) Congress created a Food and Drug Administration (FDA) approval pathway for biosimilars, which are versions of biologics that are made by competing manufacturers. However, biosimilar uptake has been slow after expiration of the market exclusivity on the original biologic. We sought to estimate Medicare Part B savings in 2020 had biologics with available biosimilars been reimbursed at comparable prices.

Understanding US Physician and Pharmacist Attitudes Toward Biosimilar Products: A Qualitative Study.

Biosimilars account for 30-40% of biologic medications dispensed in the United States (US), yet healthcare providers in relevant medical specialties have limited awareness of biosimilars and their characteristics. Likewise, many providers perceive biosimilars as less safe and effective than original biologics and are more comfortable prescribing original biologics to patients. We conducted in-person focus groups at three clinical sites in California and Texas (n = 49) to explore the reasons behind US healthcare providers' limited understanding of, cautious attitudes toward, and reluctance to prescribe biosimilars. We conducted thematic analysis by having three researchers independently analyze verbatim transcripts and identify patterns in provider responses. Providers' limited knowledge of and cautious attitudes toward biosimilars are driven by uncertainty about how biosimilarity is defined and operationalized as well as negative past experiences with generic drugs that did not perform as well as branded counterparts. Additionally, healthcare providers are unfamiliar with the Food and Drug Administration's (FDA's) approval pathway for biosimilars and are skeptical that an abbreviated approval process is rigorous enough to ensure biosimilars deliver the same efficacy and have the same side effect profiles as original biologics. Physicians also expressed concerns about pharmacy substitution of biosimilars and interchangeables, explaining they would be unaware of which medication was ultimately given to their patients. Educating physicians and pharmacists about biosimilars-including how biosimilarity is defined and operationalized, the structure of the biosimilar approval process, and how analytical data can ensure biosimilar safety and efficacy-will be important for reducing healthcare providers' concerns and increasing biosimilar adoption in the US.

Rising biosimilars in the Indian biopharmaceutical industry: emerging challenges and way forward

ABSTRACT Biopharmaceuticals have the potential to contribute immensely towards improving the health and quality of life of people. However, there is a gap in the availability of medical services in India and inequality in disseminating health benefits to the poor. Several issues are associated with biopharmaceuticals, such as increasing cost of treatments, access, affordability, safety, efficacy, quality, and intellectual property rights. Hence, the present paper addresses the crucial questions on the emerging challenges in the Indian biopharmaceutical industry regarding the patent cliff and biosimilars. What are the technological and institutional challenges faced by the biosimilars producing firms? Whether biosimilars could meet the regulatory requirements of safety, efficacy, and whether they will meet global regulatory standards? This article further analyses the regulatory pathways for commercial approval of biosimilars.

미국 바이오 시밀러 의약품 허가특허연계제도와 미국 연방대법원 Sandoz 판결

전 세계 의약품 시장에서 바이오 의약품이 차지하는 비중이 급속도로 증가하고 있다. 이에 2010년 미국 의회는 BPCIA 법의 제정을 통하여 바이오 시밀러 의약품 허가특허연계제도를 도입함으로써, 바이오 의약품에 대한 일반대중의 접근성을 향상시키고 미국 바이오 의약품 산업에서의 혁신을 도모하고자 하였다. 2017년 6월 12일 미국연방대법원은 Sandoz 판결을 통하여 바이오 시밀러 의약품 판매허가신청인이 FDA의 판매허가를 받기 이전에도 바이오 의약품 제조사에 대하여 바이오 시밀러 의약품 판매를 통지할 수 있다고 판결함으로써, 바이오 시밀러 의약품의 출시시점이 앞당겨 질 수 있는 법적 환경을 조성하였다. 따라서 Sandoz 판결은 바이오 시밀러 의약품 제조사에게 유리한 판결이다. 나아가 Sandoz 판결은 바이오 의약품 산업의 혁신이라는 “산업적 측면”과 일반대중의 바이오 의약품에 대한 접근성 향상이라는 일반대중이 인간으로서 정당하게 누려야 할 건강과 복지라는 “기본권적 측면”에 대하여 “적절하고도 신중한 균형”을 도모한 판결이라고 평가할 수 있다. 결국 Sandoz 판결에서의 연방대법원의 특허정책은 “좋은 정책”이다.BR 현재 우리나라는 미국 제너릭 의약품 허가특허연계제도와 유사한 의약품 허가특허연계제도를 운영하고 있다. 이 제도는 2007년에 체결된 한-미 FTA 협정문에 대한 이행을 위하여 도입되었다. 그러나 우리나라는 한-미 FTA협정문의 이행사항이 아님에도 불구하고 의약품 허가특허연계제도를 바이오 의약품에 대해서도 적용하고 있다. 우리나라 의약품 허가특허연계제도에 대하여 의약품 산업에 있어서 경쟁력이 낮은 우리나라 제약사에게는 불리한 제도라는 우려가 많이 제기되고 있기 때문에, 의약품 허가특허연계제도를 바이오 의약품에 적용하는 것은 적절하지 않다. 따라서 미국처럼 우리나라도 바이오 의약품을 전통적인 의약품과 분리하여 독자적인 제도에 의하여 규율하는 것이 바람직하다.

Biosimilars of monoclonal antibodies in inflammatory diseases and cancer: current situation, challenges, and opportunities.

The approval pathway for biosimilars of monoclonal antibodies in theEuropeanUnion is aimed at ruling out the presence of significant differenceswith the original biological in quality attributes, efficacy, immunogenicityand safety. It also provides the rationale for extrapolating the evidenceobtained with a biosimilar in at least one indication to the rest of theapproved indications of its original biological, thus simplifying the developmentprogramme of biosimilars. Biosimilars of monoclonal antibodiesavailable in the European Union for the treatment of inflammatory diseasesand cancer have fulfilled all the requirements for approval, and manyof them have additional evidence available. Moreover, real world dataconfirms the safety and efficacy of these drugs in the indications they arebeing used for. In Spain, many scientific societies endorse the regulatorypathway of biosimilars and acknowledge their role in the efficiency of thehealthcare system. Even so, some barriers remain that limit their use. Theimplementation of different measures at the patient, prescriber, institutional, and national levels might increase the penetration of biosimilars, freeing up resources that may be invested in other therapies and, potentially, boost innovation.

Recognizing and addressing challenges to the adoption of trastuzumab biosimilars and HER2-targeted therapies.

Oncology biologics are one of the fastest-growing segments of pharmaceutical development, bringing more options to patients, including those with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. The advent of multiple oncology biosimilars is affecting this patient population, as 5 trastuzumab biosimilars had been FDA approved as of the end of 2019; only 2, however, have been commercially marketed. Trastuzumab serves as the foundation for treatment for patients with HER2-positive breast cancer. HER2-targeted antibody-drug conjugates have been developed to enhance efficacy, improve safety, and/or create more convenient administration. Three biologic drug entities have been approved using trastuzumab, including 2 antibody-drug conjugates and a subcutaneous trastuzumab formulation that includes hyaluronidase. More products are being developed, so biosimilars and other HER2-targeted therapies may further disrupt the biologic market. Many challenging questions surround the adoption of oncology biosimilars, including regulatory pathways, efficacy, safety, cost-benefit, and comparability. The Biologics Price Competition and Innovation Act established an abbreviated regulatory approval pathway for biosimilars to create a catalyst for innovation and competition in the biologics market and to lower the costs of biologics. Challenges to adoption of therapeutic oncology biosimilars continue in the United States and include a lack of directed education to providers and patients, residual concerns regarding efficacy and safety, and practices including "pay-for-delay." The uptake of oncology biosimilars is also affected by multiple issues stemming mainly from cost of care, including drug cost, patient access, formulary inclusion, and treatment management algorithms. Managed care organizations and payers need to be familiar with the biosimilar approval process, the concerns of stakeholders (eg, providers and patients), and factors influencing HER2-directed therapies, including the use of biosimilars and antibody-drug conjugates in today's market.

Why Are Biosimilars Not Living up to Their Promise in the US?

Biologics are among the most expensive prescription drugs in the United States, posing significant barriers to patient access to necessary treatments. An abbreviated approval pathway for biosimilars, near-identical versions of biologics made by different manufacturers, was created by Congress in 2010 to stimulate competition in hopes of driving down costs and expanding access. However, as of February 2019, only 17 biosimilars have been approved, with only 7 currently on the market. Of the few biosimilars currently available to patients, overall utilization has been limited. This article examines the current landscape of the biosimilar market, characterizes tactics employed by biologics manufacturers to delay market entry and deter prescribing of biosimilars, and assesses ethical issues related to increasing the adoption of biosimilars.

Adalimumab Biosimilars in Europe: An Overview of the Clinical Evidence.

Adalimumab, the first fully humanised monoclonal antibody against tumour necrosis factor alpha (TNF-α), has played a leading role in the revolution brought about by the introduction of biologics, and has received the widest range of indications among TNF-α inhibitors. Post-registration, observational and registry studies of real-life use have largely supported the outcomes seen in registrational clinical trials. With the recent loss of exclusivity for the originator medicinal product in Europe, a number of biosimilar adalimumab molecules have been licensed for use in the same indications as the originator molecule across rheumatology, dermatology, gastroenterology and ophthalmology. Clinicians in these areas first gained experience with biosimilar infliximab, followed by etanercept and rituximab. However, adalimumab is likely to present unique challenges given the numbers of patients treated and the range of biosimilar adalimumab products available. The biosimilar approval pathway has an emphasis on the pre-clinical analytic data in combination with clinical studies conducted to confirm therapeutic equivalence. To date, several adalimumab biosimilars have entered the EU market following successful marketing authorisation applications and recent expiration of originator patent protection. This overview covers the extent of use of adalimumab and summarises the regulatory process involved in the development of biosimilars as well as their use in clinical practice. The authors also discuss clinical data available so far on adalimumab biosimilars and their envisaged impact in the field of immune-mediated inflammatory diseases.

From bioequivalence to biosimilars: How much do regulators dare?

The main advantage of an abbreviated licensing pathway is the possibility of extrapolating efficacy and safety data from an original medicinal product to a subsequent "copy" version, thereby reducing the clinical development programme in particular. For small-molecule chemically synthesized generics, such an abbreviated licensing pathway was established decades ago, whereas it was only more recently implemented for similar biological medicinal products, so-called biosimilars. Clinicians and patients have repeatedly expressed concerns about the efficacy and safety of biosimilars, especially in 'extrapolated' indications for which no own clinical data have been generated. Generic drugs usually contain well-defined active ingredients whose "identity" with that of the originator, the so-called reference product, is easily verifiable. Biological substances are generally more complex and difficult to characterize. They are produced in living organisms and therefore naturally exhibit some intrinsic variability, i.e. microheterogeneity. Since the chosen expression system and the manufacturing conditions influence the quality characteristics of a biological substance, mostly its posttranslational modifications such as the glycosylation pattern, it is unlikely that two independent manufacturing processes can achieve completely identical biologicals. A biosimilar, especially if it is a glycoprotein, can therefore, at best, be highly similar to the reference product. It seems that the not-identical-but-(highly)-similar-paradigm for biosimilars is often not well understood and causes confusion. However, while at first glance an abridged approval pathway for biosimilars appears to be daring, it is in fact based on sound scientific reasoning. A biosimilar applicant has to provide a considerably larger package of comparative data than a generic applicant to ensure that the biosimilar can indeed rely, for the purpose of licensing, on the efficacy and safety experience gained with the reference product. While for a generic, the demonstration of similar in vitro dissolution and in vivo bioavailability (so-called 'bioequivalence') is sufficient to conclude therapeutic equivalence with the reference product, for a biosimilar, comparable physicochemical, biological and functional characteristics as well as efficacy and safety/immunogenicity with the reference product must be demonstrated. In addition, unlike generics, any extrapolation to other indications of the reference product must be scientifically justified. More than 10 years of successful clinical experience with biosimilars in the EU support the credibility of the scientific principles guiding the biosimilar concept. So far, there has been no need for either withdrawal of an approved biosimilar or for additional labelling because of efficacy or safety concerns.

Real-world comparison of biosimilar filgrastim and reference filgrastim in cancer patients receiving chemotherapy.

85 Background: The approval pathway for biosimilars was established in 2010 to facilitate drug competition and generate cost savings. Biosimilar filgrastim products (filgrastim-sndz or tbo-filgrastim) were the first approved biosimilars in the US. This study examined study outcomes (incidence of febrile neutropenia (FN), growth factor related adverse events (AE) and filgrastim treatment cost) between users of biosimilar and reference filgrastim drugs among the commercially-insured US population. Methods: A retrospective observational design was used to analyze administrative claims data on adults with cancer treated with chemotherapy between 09/01/2012 - 4/30/2017. The population was grouped into biosimilar filgrastim users (B) and filgrastim users (F) according to the earliest filgrastim use (index date). FN risk factors were assessed within 6 months prior to the index date. Study outcomes were assessed within 21 days post index date using multivariable regression modelling. Results: Among 1,694 biosimilar users and 10,460 filgrastim users, no meaningful differences in baseline FN risk factors were observed. In adjusted results, no difference in incidence of FN was observed between the two groups (B: 13.3%; F: 11.0%; odds ratio [OR]: 1.17; 95% confidence intervals [CI] 0.99-1.38; p = 0.06). Rates of AE were similar between the two groups (B: 6.9%; F: 6.4%; OR: 1.04; 95% CI: 0.84-1.29, p = 0.72). The mean number of filgrastim doses administered was 3.4 in both groups (Relative difference: 0.01; 95% CI: -0.02-0.04; p = 0.53). The mean filgrastim drug costs were similar between the two groups (B: $2,491; F: $2,510, Cost Ratio [CR]: 0.96; 95% CI: 0.91-1.01; p = 0.12). However, the mean filgrastim drug cost was 6.7% less for filgrastim-sndz when compared to reference filgrastim (sndz: $2,342; CR: 0.91; 95% CI: 0.84-0.99; p = 0.04); but not for tbo ($2,549; CR: 0.97; 95% CI: 0.91-1.04; p = 0.40). Conclusions: Biosimilar filgrastim is similar to the reference filgrastim in drug safety and effectiveness. The early adoption and saving impact of biosimilar filgrastim has been modest, which highlights the structural and regulatory challenges to biosimilar uptake.

Perspectives on the Current State of the Biosimilar Regulatory Pathway in the United States.

The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) created an abbreviated licensure pathway in the United States that allows for the development and approval of biologic products shown to be biosimilar to or interchangeable with a US Food and Drug Administration (FDA)-licensed reference product (Table 1). Here we discuss implementation of the US biosimilar approval pathway and the role of various types of data, including clinical pharmacology data, in biosimilar development.

Improving Access to Cancer Treatments: The Role of Biosimilars.

Biologics play a key role in cancer treatment and are principal components of many therapeutic regimens. However, they require complex manufacturing processes, resulting in high cost and occasional shortages in supply. The cost of biologics limits accessibility of cancer treatment for many patients. Effective and affordable cancer therapies are needed globally, more so in developing countries, where health care resources can be limited. Biosimilars, which have biologic activity comparable to their corresponding reference drugs and are often more cost effective, have the potential to enhance treatment accessibility for patients and provide alternatives for decision makers (ie, prescribers, regulators, payers, policymakers, and drug developers). Impending patent expirations of several oncology biologics have opened up a vista for the development of corresponding biosimilars. Several countries have implemented abbreviated pathways for approval of biosimilars; however, challenges to their effective use persist. Some of these include designing appropriate clinical trials for assessing biosimilarity, extrapolation of indications, immunogenicity, interchangeability with the reference drug, lack of awareness and possibly acceptance among health care providers, and potential political barriers. In this review, we discuss the potential role and impact of biosimilars in oncology and the challenges related to their adoption and use. We also review the safety and efficacy of some of the widely used biosimilars in oncology and other therapeutic areas (eg, bevacizumab, darbepoetin, filgrastim, rituximab, and trastuzumab).

Comparative effectiveness and safety of erythropoiesis-stimulating agents (biosimilars vs originators) in clinical practice: a population-based cohort study in Italy

ObjectivesTo evaluate the benefit/risk profile of epoetin α biosimilar with the erythropoiesis-stimulating agents (ESAs) originators when administered to naïve patients from clinical practice.DesignPopulation-based observational cohort study.SettingAll residents in the Lazio...

Biosimilars: Opportunities and Challenges for Nurse Practitioners

The science, regulatory, and pharmacovigilance processes for biosimilars are evolving. The Biologics Price Competition and Innovation Act created an abridged approval pathway for biosimilars. The first biosimilar was Food and Drug Administration approved in 2015 with others currently pending approval. As biosimilars become marketed, nurse practitioners will be faced with many challenges, including patient questions regarding them. Nurse practitioners have an important role in the identification of possible safety profile differences between biosimilars and innovator biologicals, especially for immunogenicity. A number of practical considerations need to be addressed including substitutability; off-label prescribing; patient-specific record keeping; and computerized prescriber order entry, education, and reimbursement.

A Randomized Trial of Tbo-Filgrastim Versus Filgrastim for Autologous Stem Cell Mobilization in Patients with Multiple Myeloma or Non-Hodgkin Lymphoma

Background: Tbo-filgrastim, biosimilar to filgrastim, was approved by the FDA in 2012 as a new drug due to the lack of a biosimilar approval pathway at time of submission. Like filgrastim, tbo-filgrastim is currently indicated for the treatment of neutropenia following chemotherapy; however, filgrastim is also indicated for mobilization of hematopoietic progenitor cells for autologous stem cell transplantation (ASCT) while tbo-filgrastim is not. In Europe, tbo-filgrastim carries all the indications that filgrastim does, however, no prospective studies have been completed comparing tbo-filgrastim and filgrastim for ASCT mobilization. Therefore, we conducted a single-institution randomized phase 2 trial.Objectives: 1) To compare peripheral blood (PB) CD34+ counts, CD34+ apheresis yield, toxicity, and post-ASCT engraftment in patients mobilized with tbo-filgrastim versus filgrastim.Methods: Participants were at least 18-years-old and had multiple myeloma (MM) or non-Hodgkin's Lymphoma (NHL). Those with impaired hematologic function and those who had undergone a previous ASCT mobilization were excluded. Participants were randomized (1:1) to tbo-filgrastim or filgrastim. Tbo-filgrastim/filgrastim (10mcg/kg) was administered daily for 5 days. On the evening of Day 4, plerixafor (0.24 mg/kg) was administered; apheresis (20L) was performed on Day 5. If a participant failed to achieve the target collection goal (5.0x106 cells/kg) on Day 5, he/she continued to receive daily tbo-filgrastim/filgrastim, plerixafor, and apheresis for a maximum of 3 additional days. Participants who subsequently underwent ASCT were followed for platelet and neutrophil engraftment.Statistics: PB CD34+ counts and CD34+ apheresis yields were compared using Mann-Whitney U, engraftment using log-rank.Results: At the time of abstract submission, corresponding with interim analysis 1, 51 participants were enrolled and 49 were evaluable for analysis; 24 received tbo-filgrastim, 25 filgrastim. The median age was 60 years (range 40-77); 63% (31) were male; 86% (42) had MM, 14% (7) NHL. Both treatment arms were similar in demographics and baseline blood counts.Post-mobilization PB CD34+ counts were similar between both arms. The median PB CD34+ count on day 4 (pre-plerixafor) was 20/mcL for tbo-filgrastim and 22/mcL for filgrastim (p=0.647); on Day 5 pre-apheresis it was for 94/mcL for tbo-filgrastim and 92/mcL for filgrastim (p=0.726). CD34+ apheresis yield was also similar; the median Day 5 CD34+/kg apheresis yield was 10.9x106 for tbo-filgrastim and 12.0x106 for filgrastim (p=0.889).Seventy-five percent of the tbo-filgrastim arm reached the collection goal after one day of apheresis, 76% of the filgrastim arm did (p=0.935). Ninety-six percent of patients on the tbo-filgrastim arm reached the goal in 4 or less days of apheresis, 92% of the filgrastim arm did (p=0.576). All patients treated collected > 2.0x106 cells/kg, the minimum required for ASCT, following < 2 days of apheresis. Both treatment arms had similar toxicity.Thirty-nine patients have subsequently undergone ASCT and evaluable for engraftment, 18 on the tbo-filgrastim arm and 21 on the filgrastim arm. The median interval of neutrophil engraftment for tbo-filgrastim was 12 days compared to 11 for filgrastim (p=0.178); the median interval of platelet engraftment was 17 days for both arms (p=0.238).Mobilization, collection, toxicity, and engraftment data are summarized in Table 1.Conclusion: Tbo-filgrastim appears to be similar to filgrastim for ASCT mobilization in patients with MM or NHL. Planned study enrollment is 100 evaluable patients; updated study results will be presented.Table 1Tbo-FilgrastimFilgrastimPB CD34+/mcl on Day 41(median & range)20 (4-68)22 (1-115)PB CD34+/mcl on Day 5 (median & range)94 (18-187)92 (11-314)CD34+/kg x106 yield on Day 5 (median & range)10.9 (1.4-21.2)12.0 (1.3-28.4)CD34+/kg yield >2.0 on Day 596%92%CD34+/kg yield >5.0 on Day 575%76%CD34+/kg yield >2.0 in < 4 days100%100%CD34+/kg Yield >5.0 in < 4 days96%92%Post-ASCT EngraftmentDays to Neutrophil Engraftment (median & range)12 (10-20)11 (10-13)Days to Platelet Engraftment (median & range)17 (13-23)17 (13-22)1-Prior to plerixafor dose DisclosuresVij:Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy; Takeda, Onyx: Research Funding. Abboud:Teva Phamaceutical: Research Funding.

Development of biosimilars in an era of oncologic drug shortages.

Acute and chronic shortages of various pharmaceuticals and particularly of sterile injectable products are being reported on a global scale, prompting evaluation of more effective strategies to manage current shortages and development of new, high-quality pharmaceutical products to mitigate the risk of potential future shortages. Oncology drugs such as liposomal doxorubicin and 5-fluorouracil represent examples of first-choice drugs critically affected by shortages. Survey results indicate that the majority of hospitals and practicing oncologists have experienced drug shortages, which may have compromised patient safety and clinical outcomes, and increased health care costs, due to delays or changes in treatment regimens. Clinical trials evaluating novel agents in combination with standard-of-care drugs are also being affected by drug shortages. Clinical and ethical considerations on treatment objectives, drug indication, and availability of alternative options may help in prioritizing cancer patients involved in active drug shortages. The United States Food and Drug Administration and the European Medicines Agency have identified manufacturing problems, delays in supply, and lack of available active ingredients as the most frequent causes of recent or ongoing drug shortages, and have released specific guidance to monitor, manage, and reduce the risk of shortages. The upcoming loss of exclusivity for a number of anticancer biologics, together with the introduction of an abbreviated approval pathway for biosimilars, raises the question of whether these products will be vulnerable to shortages. Future supply by reliable manufacturers of well characterized biosimilar monoclonal antibodies, developed in compliance with regulatory and manufacturing guidelines and with substantial investments, may contribute to prevent future biologics shortages and ensure access to effective and safe treatment options for patients with cancer. Preclinical and clinical characterization is ongoing for potential biosimilars of trastuzumab, rituximab, and bevacizumab, with promising results.

Do low- to middle-income countries need a biosimilar approval pathway based on a full comparability exercise?

Do low- to middle-income countries need a biosimilar approval pathway based on a full comparability exercise?

Biosimilars: An Emerging Category of Biologic Drugs for Emergency Medicine Practitioners

Biologics are the fastest growing segment of annual United States (US) drug expenditure. Biologics are complex proteins derived from living sources that are important therapy for a variety of diseases. The US is now poised to introduce biosimilars, which are copies of biologics that are not manufactured by the innovator company and are approved under an abbreviated regulatory process. Biosimilars are intended to offer comparable safety and efficacy to the reference biologic at a lower cost. Because of the complexity of producing biologics, the manufacturing process for biosimilars may differ from that of the reference biologic, which may result in subtle changes in biological characteristics and clinical activity. Questions exist regarding whether these slight differences allow the products to be interchanged with the reference product and if unique adverse events will occur with use. While the Biologics Price Competition and Innovation Act outlined the abbreviated approval pathway for biosimilars, guidance from the US Food and Drug Administration (FDA) is needed on specific details of the approval process. The FDA has recently provided guidance about the scientific and quality requirements for demonstrating biosimilarity, but a number of unanswered questions still remain, including concerns about immunogenicity, product naming, and the exact cost savings from biosimilars. Emergency Medicine practitioners must have a sound understanding of these issues to ensure patient safety and avoid complications in care.

Destined for Failure? An Analysis of the Biologics Price Competition and Innovation Act of 2009

In 2010, Congress enacted the Biologics Price Competition and Innovation Act (“BPCIA”) as part of the large health care reform bill. The BPCIA creates a statutory pathway for FDA approval of “biosimilars”––which are generic versions of biologic drugs. Congress expects this new approval pathway for biosimilars to help lower biologics prices, just as generic drugs have significantly lowered pharmaceutical prices. This Note argues that, for three main reasons, the BPCIA will not succeed in lowering drug prices to the same degree that generic pharmaceuticals have. First, biosimilars are more expensive to develop than generic pharmaceutical drugs. Manufacturers will be hesitant to enter the biosimilars market, leading to less competition. Second, biosimilars will struggle more than generics to capture market share from the branded drug. Third, lengthy exclusivity periods awarded to the branded biologic and the first interchangeable biosimilar will substantially delay biosimilar market entry. This Note then concludes with suggestions for improving the BPCIA, both through potential amendments and regulatory process.

Differentiating Factors Between Erythropoiesis-Stimulating Agents: An Update to Selection for Anaemia of Chronic Kidney Disease

Erythropoiesis-stimulating agents (ESAs) have become a hallmark of anaemia therapy in patients with chronic kidney disease (CKD). Although different ESAs are available for the treatment of renal anaemia, each nephrologist should select a single ESA for an individual patient. Epoetin alfa and epoetin beta have been used 1-3 times weekly but extended-interval dosing up to every 4weeks is also effective in a substantial majority of CKD patients. However, the epoetin dose necessary to achieve or maintain target haemoglobin (Hb) levels increases substantially as the dosing interval increases. Subcutaneous administration of short-acting ESAs is more effective than the intravenous route of administration. Darbepoetin alfa and the continuous erythropoietin receptor activator (CERA) have been developed as a treatment for anaemia with extended administration intervals (every 2weeks and every 4weeks, respectively). Dose requirements for these long-acting ESAs are independent of the route of administration. Patents of short-acting ESAs have expired, which has opened the field for biosimilars. Epoetin biosimilars approved by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) have been shown to have a comparable efficacy and safety profile to their originators. An alarming increase in pure red cell aplasia (PRCA) in Thailand with follow-on epoetins manufactured in Asia (but also those manufactured in Latin America) indicates that stringent country-specific approval and pharmacovigilance protocols for ESAs manufactured in non-North American and non-EU European countries are urgently needed. Two PRCA cases occurring with subcutaneous HX575 (one certain, one likely) indicate that chances of inducing a more immunogenic product are unpredictable, even with a biosimilar epoetin approved under the EMA biosimilar approval pathway. Phase III clinical trials with peginesatide, a pegylated synthetic peptide-based ESA without any homology to erythropoietin raised safety concerns in non-dialysis CKD patients but not in dialysis patients.