Regulatory Exclusivity Research Articles

Introducing biosimilar competition for cell and gene therapy products.

This article provides an early analysis of the potential for creating future biosimilar competition for cell and gene therapies (CGTs) to lower prices and improve patient access, building on a unique set of interviews with relevant experts. Our discussion addressed regulatory, manufacturing, intellectual property, and market size challenges. Due to CGTs' complexity, meeting the regulatory requirement of 'high similarity with no clinically meaningful differences' will be difficult. Gene therapies are likely better candidates for biosimilar development than cell therapies. Biosimilarity should be met when gene therapy biosimilars contain the same genetic sequence as a reference product, and the variability in the vector meets the high similarity standard. Manufacturing challenges, including the lack of standardized platforms, high production costs, and complexity, pose significant obstacles. It may also be important to demonstrate biosimilarity within the manufacturing process. Intellectual property barriers, specifically patenting, trade secrecy, and regulatory exclusivity, could hinder biosimilars' ability to gain market share, although recent Supreme Court decisions limiting the breadth of patent claims could ease barriers to future CGT competition, including from biosimilars. Finally, inadequate market sizes might create hurdles, especially for curative treatments, as patient pools shrink following treatment by the reference CGT.

The Interface Between Patents and Regulatory Exclusivities and the View on the New EU Proposals Concerning Patent Compulsory Licensing and Regulatory Exclusivities

Abstract Exclusivity rights such as patents have gained special attention in the post-pandemic period. Patents are intended to be a tool to prevent potential market failure in intangible goods and encourage investment in innovation. At the same time, recently they have been accused of blocking access to COVID-19 vaccines and have even fuelled public debate on the introduction of various measures to limit the exclusivity rights arising from the grant of a patent. However, patents are not the only exclusivity available to (bio)pharmaceuticals. Regulatory exclusivities, though less well-known to broader society, are no less important than patents and no less relied on by the pharmaceutical industry. A fortiori, de lege lata regulatory exclusivities have no exceptions, which means they are more robust than patents and can potentially provide even stronger protection than that afforded by patents. This contribution provides a comparative view on patents and the less explored ‘8+2+1’ regulatory exclusivities, outlining common and distinctive features and the interaction between the two regimes. Some preliminary reflections are made on potential legislative adjustments, without which the much-debated compulsory licensing may prove to be of little use. Finally, insights are provided into the European Commission’s proposals of spring 2023 for general pharmaceutical legislation and compulsory licensing. Some preliminary insights into the proposed changes to the regulatory exclusivity system are also provided. Special attention is paid to the proposal aimed to reach compatibility between regulatory exclusivities and compulsory licensing.

Combatting Antibiotic Resistance: Regulatory Exclusivities for New Antibiotic Development in the United States and Europe

Abstract Antimicrobial resistance is a global concern that has led to millions of deaths worldwide. Genetic changes occur naturally in pathogens such as viruses, bacteria, parasites, and fungi. To overcome these concerns, there is a need to develop a new generation of antimicrobials. In an effort to encourage innovation, both the United States (US) and the European Union have introduced exclusivity programs. The US offered 5 years of additional nonpatent exclusivity for Qualified Infectious Disease Products under the Generating Antibiotic Incentives Now Act. In parallel, the European Commission offers a patent extension of 12 months across Europe (EU) countries or the option to sell the vouchers to other pharmaceutical companies through transferable exclusivity extension vouchers. This review focuses on the most important innovative strategies of antibiotic development the drug approvals, their mode of action, spectra of activity, and targeting of microorganisms, in past 5 years were mentioned, and discusses how to overcome the challenges of drug approval under antibiotic exclusivity in the US and EU, which will benefit the companies to develop novel drugs in several nations.

Patents and regulatory exclusivities on FDA-approved insulin products: A longitudinal database study, 1986-2019.

Insulin is the primary treatment for type 1 and some type 2 diabetes but remains costly in the United States, even though it was discovered more than a century ago. High prices can lead to nonadherence and are often sustained by patents and regulatory exclusivities that limit competition on brand-name products. We sought to examine how manufacturers have used patents and regulatory exclusivities on insulin products approved from 1986 to 2019 to extend periods of market exclusivity. We used the publicly available Food and Drug Administration (FDA) Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) to identify all approved biosynthetic insulin products. Individual products approved under the same New Drug Application (NDA)-e.g., a vial and pen-were considered as separate products for the purposes of analysis. We recorded all patents and regulatory exclusivities listed in the Orange Book on each product and used Google Patents to extract the timing of patent application and whether patents were obtained on delivery devices or others aspects of the product. The primary outcome was the duration of expected protection, which was determined by subtracting the FDA approval date for each product from its last-to-expire patent or regulatory exclusivity (whichever occurred later). We performed a secondary analysis that considered overall protection on insulin lines-defined as groups of products approved under the same NDA with the same active ingredients manufactured by the same company. We also examined competition from follow-on insulin products-defined as products approved with the same active ingredients as originators but manufactured by different companies (approved via a specific drug approval pathway under section 505(b)(2) of the Food, Drug, and Cosmetic Act). During the study period, the FDA approved 56 individual products across 25 different insulin lines and 5 follow-ons across 3 different insulin lines. Thirty-three (59%) of the 56 products were drug-device combinations. Manufacturers of 9 products approved during the study period obtained patents filed after FDA approval that extended their duration of expected protection (by a median of 6 years). Approximately 63% of all patents on drug-device combinations approved during the study period were related to delivery devices. The median duration of expected protection on insulin products was 16.0 years, and the median protection on insulin lines was 17.6 years. An important limitation of our analysis is that manufacturers may continue to add patents on existing insulin products while competitors may challenge patents; therefore, periods of protection may change over time. Among several strategies that insulin manufacturers have employed to extend periods of market exclusivity on brand-name insulin products are filing patents after FDA approval and obtaining a large number of patents on delivery devices. Policy reforms are needed to promote timely competition in the pharmaceutical market and ensure that patients have access to low-cost drugs.

EE537 Quantifying Annual Medical Economic Burden of Patents and Regulatory Exclusivities on Ics/Laba Inhalers Among End-Stage COPD Patients

In the United States (US), COPD imposes a substantial societal health and economic burden. High prices of inhalers, the mainstay treatment, due to patent protection and limited generic availability, can lead to high out-of-pocket (OOP) costs. This study aims to model one-year economic burden of market exclusivity for inhaled corticosteroids (ICS) combined with long-acting beta2 agonists (LABA) among end-stage COPD patients.

Recent Developments in FDA Regulatory Exclusivities

Biotechnology Law ReportVol. 42, No. 3 The Holman ReportRecent Developments in FDA Regulatory ExclusivitiesBy CHRISTOPHER M. HOLMANBy CHRISTOPHER M. HOLMANChristopher M. Holman is a Professor of Law at the University of Missouri-Kansas City School of Law; a Senior Scholar at the Center for the Protection of Intellectual Property at the Antonin Scalia Law School, George Mason University; and the Executive Editor of Biotechnology Law Report.Search for more papers by this authorPublished Online:9 Jun 2023https://doi.org/10.1089/blr.2023.29314.cmhAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetails Volume 42Issue 3Jun 2023 InformationCopyright 2023, Mary Ann Liebert, Inc., publishersTo cite this article:By CHRISTOPHER M. HOLMAN.Recent Developments in FDA Regulatory Exclusivities.Biotechnology Law Report.Jun 2023.118-131.http://doi.org/10.1089/blr.2023.29314.cmhPublished in Volume: 42 Issue 3: June 9, 2023Online Ahead of Print:May 26, 2023PDF download

The NBER Orange Book Dataset: A user’s guide

This paper introduces a newly digitized, open-access version of the Food and Drug Administration’s “Orange Book”—a linkage between approved small-molecule drugs and the patents that protect them. The Orange Book also reports any applicable regulatory exclusivity that prevents competitive entry. We summarize the Orange Book’s coverage and discuss the opportunities and challenges associated with using these data for research. Empirical validations against various administrative datasets suggest that Orange Book records are, largely, complete and accurate. We conclude with a specific use case—calculating legal exclusivity periods for drugs—to highlight the types of choices that researchers must make when using this resource.

Clinical Trial Data Transparency in the EU: Is the New Clinical Trials Regulation a Game-Changer?

The benefits of access to clinical trial data are related to their inestimable value from the perspective of clinical trial participants, society as a whole, public health systems and scientific progress. In light of the development of innovative data analysis technologies, access to raw clinical trial data opens up an ever-widening array of possibilities: it can profoundly facilitate machine data analysis for, inter alia, hypothesis generation, risk modelling, counterfactual simulation and – finally – drug repurposing and development. The enactment of the new Clinical Trials Regulation (EU) No. 536/2014 (CTR) and introduction of the Clinical Trials Information System (CTIS) were heralded as ensuring a level of transparency in clinical trials that is sufficient to contribute to protecting public health and fostering the innovation capacity of European medical research, while recognizing the legitimate economic interests of sponsors. This paper presents the hitherto binding rules for the disclosure of clinical trial data and, against this background, their new framework, introduced by the CTR. In addition to assessing whether the CTR’s objectives are fulfilled, this paper examines whether the latest changes impact the hitherto existing rules on protection of regulatory data via regulatory exclusivities. Finally, it points out concerns regarding whether data gathered in the CTIS can be efficiently used by innovative data analysis technologies for further processing for both commercial and non-commercial purposes.

The Quest for Secondary Pharmaceuticals: Drug Repurposing/Chiral-Switches Combination Strategy.

Drug repurposing toward new medical uses and chiral switches are elements of secondary pharmaceuticals. The drug repurposing and chiral-switches strategies have mostly been applied independently in drug discovery. Drug repurposing has peaked in the search for therapeutic treatments of the Coronavirus Disease 2019 pandemic, whereas chiral switches have been overlooked. The current Perspective introduces the drug repurposing/chiral-switches combination strategy, overviewing representative cases of chiral drugs that have undergone this combination: ketamine, flurbiprofen, fenfluramine, and milnacipran. The deuterium-enabled chiral switches of racemic thalidomide analogs, a variation of the repurposing/chiral-switch combination strategy, is also included. Patenting and regulatory-exclusivity considerations of the combination strategy in the discovery of new medical uses are considered. The proposed combination creates a new synergy of its two elements, overcoming arguments against chiral switches, with better prospects for validation of patents and regulatory exclusivities. The combination strategy may be applied to chiral switches to paired enantiomers. Repurposing/chiral-switch drugs may be 'obvious-to-try'; however, their inventions may be unexpected and their patents nonobvious. Patenting repurposing/chiral-switch combination drugs is not 'evergreening', 'product hopping', and 'me-too'. The expected benefits and opportunities of the combined repurposing/chiral-switch strategy vis-à-vis its two elements are superior pharmacological properties, overcoming arguments against patent validities, challenges of chiral-switch patents, reduced expenses, shortened approval procedures, and higher expectations of regulatory exclusivities.

The Interface between Patents and Regulatory Exclusivities and the View on the New EU Proposals Concerning Patent Compulsory Licensing and Regulatory Exclusivities

The Interface between Patents and Regulatory Exclusivities and the View on the New EU Proposals Concerning Patent Compulsory Licensing and Regulatory Exclusivities

PP152 The Assessment Of The Price Of A Medicine: The Possible Application Of Cost-Based Pricing Methods

IntroductionBefore admission to the insured package, the price of a medicine is usually assessed on the basis of the value of the medicine for the patient: the effect size on health and survival must be in line with the costs. That seems like a fair starting point, but the use of such ‘value-driven’ models sometimes results in unrealistic prices. These prices in turn lead to discussions about limitations within the healthcare budget and may result in delays in the accessibility of medicines. The aim of this study was to review several alternative pricing models and propose possible applications of the models.MethodsSix pricing models were selected that encompassed cost-based or cost- and value-based aspects. The models were reviewed within the context of the published group of medicines, followed by a discussion on their potential to aid in creating benchmarks for pricing negotiations.ResultsFive cost-based pricing models and one value-based model with a cost-based aspect were found with potential applications. (i) The AIM-model for innovative medicines. (ii) The adjusted AIM-model for repurposed medicines. (iii) The Cancer drug pricing model for innovative oncolytics with information about health benefit. (iv) The discounted cash flow model for orphan medicines with information about health benefit. (v) The value-based rate of return pricing for innovative orphan medicines with information about health benefit. (vi) The P-quad model for drugs with a high budget impact for which there is no generic competition after intellectual property an regulatory exclusivity end.ConclusionsWe argue that it would be more logical for different categories of medicines to base prices on average costs, possibly combined with a bonus for innovation: the cost-based pricing method. The next step is to discuss the possible application of cost-plus methods with stakeholders including patients, industry, payers, and healthcare professionals.

Analysis of Patent and Regulatory Exclusivity for Novel Agents in China and the United States: A Cohort Study of Drugs Approved Between 2018 and 2021

Patent and regulatory exclusivity shall constitute incentives for pharmaceutical companies to develop new drugs. This study aims to investigate the differences in the patent term extension (PTE) and regulatory exclusivity between China and the United States, and to evaluate their potential impact on the market exclusivity period of novel drugs. Small-molecule novel drugs with their first indication approved in China and the United States between 2018 and 2021 were evaluated regarding their PTE and regulatory exclusivity. The PTE length of the China-approved drugs was calculated by simulation, whereas that of the US-approved drugs was extracted from the United States Patent and Trademark Office. Thirty-two and 107 novel drugs approved in China and the United States, respectively, were included in the study. The PTE length of the US-approved drugs calculated by the China-PTE method was significantly longer than that calculated by the US-PTE method. Patent extensions should be granted for 91% of new drugs in China and 82% in the United States. The simulated median PTE length of novel drugs approved in China was significantly higher than that of the United States (5.0 vs. 2.9years, P<0.05). It can be expected that the implementation of the PTE policy in China would significantly extend the period of market exclusivity for novel drugs similar to that of the United States. China should fully evaluate the potential impact of the PTE policy on the market exclusivity of novel drugs and provide better incentives to the development of novel drugs in addressing unmet clinical needs when developing its regulatory exclusivity policy.

Patents And Regulatory Exclusivities On Inhalers For Asthma And COPD, 1986-2020.

Inhalers are the mainstay of treatment for asthma and chronic obstructive pulmonary disease (COPD). These products face limited generic competition in the US and remain expensive. To better understand the strategies that brand-name inhaler manufacturers have employed to preserve their market dominance, we analyzed all patents and regulatory exclusivities granted to inhalers approved by the Food and Drug Administration between 1986 and 2020. Of the sixty-two inhalers approved, fifty-three were brand-name products, and these brand-name products had a median of sixteen years of protection from generic competition. Only one inhaler contained an ingredient with a new mechanism of action. More than half of all patents were on the inhaler devices, not the active ingredients or other aspects of these drug-device combinations. Manufacturers augmented periods of brand-name market exclusivity by moving active ingredients from one inhaler device into another ("device hops"). The median time from approval of an originator product to the last-to-expire patent or regulatory exclusivity of branded follow-ons was twenty-eight years (across device hops on fourteen originator products). Regulatory and patent reform is critical to ensure that the rewards bestowed on brand-name inhaler manufacturers better reflect the added clinical benefit of new products.

Reimagining Pharmaceutical Market Exclusivities: Should the Duration of Guaranteed Monopoly Periods Be Value Based?

ObjectivesTo describe the main features of a pharmaceutical market in which the duration of guaranteed monopoly periods would correspond to a new pharmaceutical product’s value. MethodsAfter reviewing patent and regulatory exclusivity-based mechanisms for protecting prescription drug markets from competition to incentivize drug innovation in developed countries, we model market protection mechanisms within the current framework to give the longest-lasting market protections to drug developers that bring the most affordable products to market with highest public health and clinical value. ResultsAn approach tying pharmaceutical market exclusivity to value would have 3 main features. First, it would be based on regulatory exclusivity (ie, the drug regulator refrains from authorizing generic entry for a certain amount of time), rather than patents. Second, the duration of exclusivity period would be pegged to the magnitude of a product’s anticipated health impact and its proposed price by using modified methods from the field of health technology assessment. Third, the duration of the value-based exclusivity period would be reassessed routinely 3 years after the product’s launch to account for its real-world effectiveness. ConclusionsLinking a drug’s proposed price to the duration of its regulatory-based exclusivities would both incentivize the development of high impact, low-cost products and motivate drug developers to introduce these products at lower prices.

Transparency and accountability in the negotiation of the US-Mexico-Canada trade agreement: the case of pharmaceuticals

BackgroundTransparency and accountability are essential components at all stages of the trade negotiation process. This study reports on the findings of an evaluation of the United States' public consultation process during the re-negotiation of the North American Free Trade Agreement (NAFTA)/United States-Mexico-Canada Agreement (USMCA) with respect to medicines and the pharmaceutical sector. MethodsA desk review was conducted to map the US negotiation rounds of the USMCA. Then, opportunities for the public to receive information and provide feedback about the proposed agreement provisions were identified. Finally, the written comments submitted by stakeholders during this public consultation process to the Federal Register (Regulations.gov) were queried and analysed using qualitative data analysis software NVivo for language related to pharmaceuticals and medicine. FindingsThe public consultation process occurred before the start of official negotiations. It was overseen by the Office of the US Trade Representative (USTR) and included both written comments and oral testimony about US negotiation objectives. There were no further official opportunities for the public to engage with the negotiation process. Of the 1458 comments publicly available through the Federal Register, 75 specifically discussed issues related to pharmaceuticals for human use. More than 50% of submissions received from members or affiliates of the pharmaceutical industry advocated for strengthened pharmaceutical intellectual property rights, greater regulatory data protection, or both. Nearly all submissions from non-industry groups indicated that access to, or the affordability of, medicines was a priority issue area in the renegotiated agreement. Most submissions that directly discussed transparency and accountability were authored by industry groups and emphasised the importance of predictability and transparency in the areas of pharmaceutical intellectual property, regulatory affairs, pricing, and reimbursement to facilitate greater innovation. InterpretationUSMCA increased regulatory data protection for innovator drugs, increased the period of regulatory exclusivity for biologics, and granted patent term restoration provisions for regulatory delays, undermining public access to medicines. Although industry comments only constitute 26% of the comments submitted during the US public consultation period related to pharmaceuticals, they reflect the dominant position adopted in the USMCA. FundingConnaught Fund Global Health Challenge Award.

Modalities, Challenges, and Possibilities

On October 25, 2019, the Texas A&amp;M Journal of Property Law and the Center for Law and Intellectual Property at Texas A&amp;M University School of Law jointly organized the “Pharmaceutical Innovation, Patent Protection, and Regulatory Exclusivities” Symposium. Although none of the organizers and participants could predict what was to come in the next few months, there was a wide consensus that the rapid changes in the pharmaceutical landscape and our continuous struggle to strike a proper balance between proprietary protection and public access in the public health arena deserves scholarly, policy, and regulatory attention. To help contextualize the articles included in this special issue and to inform readers about the inspirations and motivations behind the Symposium, Part II of this Introductory Article explores the different modalities of protection—in particular the role of patents and regulatory exclusivities in providing the needed incentives to pharmaceutical developers. Part III identifies three sets of challenges that affect the future of pharmaceutical innovation at both the domestic and international levels. Part IV utilizes a very recent event—the COVID-19 pandemic—to illustrate the wide array of policy options and possibilities both within and outside the intellectual property system. This Part makes salient the nexus between the domestic and international debates on pharmaceutical innovation.

Addressing Exclusivity Issues During the COVID-19 Pandemic and Beyond

Almost every aspect of the COVID-19 response, from vaccines, diagnostics, and therapeutics to medical equipment, tracking systems, software, and other innovations, are or will become subject to some form of exclusive rights. Many of these involve intellectual property rights (IPRs). By offering innovators the exclusive right to exploit their innovations while recouping the costs of research, development, and other expenditures, IPRs may incentivize the development of new technologies. But IPRs may also preclude others from important research, manufacturing, and distribution. In the same vein, these exclusionary rights allow right holders to set prices in the absence of competition. Since this may limit access to innovations that are crucial for tackling pandemics, IPRs are a key factor in pandemic response and preparedness. Consequently, they have generated much controversy around the globe. Many of these debates have concentrated on traditional IPRs, particularly patent rights. Numerous existing patent claims cover new chemical or molecular entities. Patents are also filed for repurposed drugs and vaccine platforms (e.g., COVID-19 mRNA platforms), with separate patent protection for the vaccine and its elements, including viral particles, adjuvants, and vaccine boosters. Even in situations where no patent protection is available, many COVID-19 therapeutics and vaccines will also obtain regulatory, data, and market exclusivities. Consequently, the specific design and new areas of application for regulatory exclusivities have become an increasingly important issue in general innovation policy debates. This chapter addresses exclusivity issues, with a particular emphasis on regulatory exclusivities for vaccines and therapeutics. We begin with a basic overview of the current regulatory exclusivity landscape in Europe and the US, followed by a discussion of current developments in COVID-19 vaccines and therapeutics. Next, we describe the influence of these technological developments on debates surrounding regulatory exclusivities while describing their relationship to other forms of exclusivities. From these assessments, we draw some lessons for market exclusivity, innovation, and access during the COVID-19 pandemic and beyond.

Why a COVID IP Waiver Is not a Good Strategy

The COVID-19 pandemic has a profound influence on all aspects of society. The development of successful vaccines in record speed is almost a miracle. But despite the successful development and approval of multiple vaccines, many people still die of this terrible disease, and there is an urgent need to see more vaccines manufactured and distributed across the globe. The proposed COVID-19 IP waiver has been touted by some to be the perfect solution to a terrible problem. We all agree that there is a terrible problem of insufficient vaccines to inoculate the world population. An IP waiver is not a good strategy however, to tackle this crisis. There are multiple more effective solution conceivable which do not require a very disruptive IP waiver. The problem of insufficient supply is much more complicated than a simple IP waiver suggests. This is a complex ecosystem, and there are many moving parts. Moreover, IP rights are only part of the problem relating to more supply of vaccine or therapeutics. In view of the complexities, it will probably take many months to negotiate any kind of IP waiver system that would be acceptable to all WTO member states, if consensus could be reached at all. And the end result is likely to satisfy very few if any countries. The legality of an IP waiver can be doubted, and it would require retro-active effect, a concept that should be extremely sparingly used. A multitude of complex issues needs to be sorted out. There are hundreds of patents to navigate. A waiver to the equally patented vaccine platform technology (covering many patents), which may be used to develop any other vaccine, will make those companies who have invested heavily into developing it very nervous indeed, to say the least. Crucial manufacturing know-how is often not protected by IP rights, but is kept secret, and it will be difficult to force companies to disclose that information, also because one does not know what to ask for. The present IP waiver proposal also provides for a disclosure of commercially very sensitive information. Companies did not have a chance to adapt their regulatory disclosure strategies to this new reality, which means that information which will be disclosed under the waiver could very well have a major negative impact on future innovation strategies, and may also hamper competitive advantage or leverage. Market exclusivity is arguably not covered by the IP waiver, which means that separate national statutory intervention will be required to ensure that this market exclusivity is set aside, absent of which the IP waiver cannot have any practical effect. A quick and determined use of compulsory licensing could be a better way forward, as they have the potential to be a powerful tool. There are inefficiencies in using the instrument however, and invoking them when the need is high will require a relatively long lead time before they sort practical effect. They also require additional statutory intervention to ensure that regulatory exclusivities do not block their practical effect. And they might not necessarily work as well with low and middle-income countries, who would have less leverage in the negotiations. More efficient solutions can be arrived at by introducing hard clauses into contracts in the context of push and pull mechanisms. Those obligations are much more likely to result in more supply in the shorter to medium term if they are agreed upon long before the vaccine enters the market. It is obviously too late for the contracts that have been concluded in the past, but it should be a template for the future.

Regulatory exclusivity protection for undisclosed test data in China: an innovative approach to implementing the TRIPS Agreement

Regulatory exclusivity, the TRIPS-plus protection for undisclosed test data, is considered as the principal means to extend market protection for brand-name pharmaceutical companies. When China joined the World Trade Organization in 2001, it promised to enact new laws or regulations that will comply with article 39.3 of the TRIPS Agreement. China's choice of implementing the TRIPS Agreement through regulatory exclusivity resulted mainly from intrinsic demands for China's strategy of innovative-driven development, and partly from the pressure of China-US trade disputes. There are two categories of regulatory exclusivities under China's laws. One is the market exclusivity for New Drugs and Traditional Chinese Medicine. The other is the data exclusivity for Innovative Drugs, Orphan Drugs, Paediatric Drugs, Innovative Biologics; and a ‘Generic Exclusivity’ for the first generic drug company that succeeds in challenging weak patents of pharmaceutical products.

A Review of the Totality of Evidence Supporting the Development of the First Adalimumab Biosimilar ABP 501.

ABP 501 [United States: AMJEVITA™ (adalimumab-atto); European Union: AMGEVITA® (adalimumab)] is the first approved biosimilar to adalimumab [reference product (RP)], a monoclonal antibody (mAb) targeting tumor necrosis factor-alfa (TNF-α). ABP 501 has received approval for use in indications that adalimumab RP is approved for, except those protected by regulatory exclusivity. A systematic step-wise totality of evidence (TOE) approach formed the basis of approval of ABP 501; this involved methodical accumulation of scientifically robust comparative data supporting similarity in analytical, preclinical, and clinical [pharmacokinetics (PK)], efficacy, safety and immunogenicity) evaluations. As a foundational first step, comprehensive analytical assessments demonstrated that ABP 501 is structurally and functionally similar to adalimumab RP in critical quality attributes. Preclinical assessments confirmed similar activity in assessing mechanisms of action and toxicology. Clinical evaluation included a phase 1 PK equivalence study in healthy subjects and two comparative phase 3 studies that evaluated ABP 501 and adalimumab RP in two sensitive patient populations, plaque psoriasis (PsO) and rheumatoid arthritis (RA). The PK profiles of ABP 501 and adalimumab RP were similar in healthy subjects as well as patients with PsO and RA. The pivotal phase 3 study in patients with PsO demonstrated that ABP 501 was clinically similar to adalimumab RP in terms of efficacy, safety and immunogenicity in both the primary and transition phases. The pivotal phase 3 study in patients with RA also established clinical similarity between ABP 501 and adalimumab RP; an open-label extension of this study demonstrated sustained efficacy over an additional 72 weeks, with no new safety or immunogenicity concerns with ABP 501 treatment. Overall, the TOE supported the conclusion that ABP 501 is highly similar to adalimumab RP and provided scientific justification for extrapolation to all the approved indications of adalimumab RP not protected by exclusivities.Funding: Amgen Inc.