The present and future of bispecific antibodies for cancer therapy.

Bispecific antibodies (bsAbs) enable novel mechanisms of action and/or therapeutic applications that cannot be achieved using conventional IgG-based antibodies. Consequently, development of these molecules has garnered substantial interest in the past decade and, as of the end of 2023, 14 bsAbs have been approved: 11 for the treatment of cancer and 3 for non-oncology indications. bsAbs are available in different formats, address different targets and mediate anticancer function via different molecular mechanisms. Here, we provide an overview of recent developments in the field of bsAbs for cancer therapy. We focus on bsAbs that are approved or in clinical development, including bsAb-mediated dual modulators of signalling pathways, tumour-targeted receptor agonists, bsAb-drug conjugates, bispecific T cell, natural killer cell and innate immune cell engagers, and bispecific checkpoint inhibitors and co-stimulators. Finally, we provide an outlook into next-generation bsAbs in earlier stages of development, including trispecifics, bsAb prodrugs, bsAbs that induce degradation of tumour targets and bsAbs acting as cytokine mimetics.

Antibodies to watch in 2024.

The 'Antibodies to Watch' article series provides an annual summary of commercially sponsored monoclonal antibody therapeutics currently in late-stage clinical development, regulatory review, and those recently granted a first approval in any country. In this installment, we discuss key details for 16 antibody therapeutics granted a first approval in 2023, as of November 17 (lecanemab (Leqembi), rozanolixizumab (RYSTIGGO), pozelimab (VEOPOZ), mirikizumab (Omvoh), talquetamab (Talvey), elranatamab (Elrexfio), epcoritamab (EPKINLY), glofitamab (COLUMVI), retifanlimab (Zynyz), concizumab (Alhemo), lebrikizumab (EBGLYSS), tafolecimab (SINTBILO), narlumosbart (Jinlitai), zuberitamab (Enrexib), adebrelimab (Arelili), and divozilimab (Ivlizi)). We briefly review 26 product candidates for which marketing applications are under consideration in at least one country or region, and 23 investigational antibody therapeutics that are forecast to enter regulatory review by the end of 2024 based on company disclosures. These nearly 50 product candidates include numerous innovative bispecific antibodies, such as odronextamab, ivonescimab, linvoseltamab, zenocutuzumab, and erfonrilimab, and antibody-drug conjugates, such as trastuzumab botidotin, patritumab deruxtecan, datopotamab deruxtecan, and MRG002, as well as a mixture of two immunocytokines (bifikafusp alfa and onfekafusp alfa). We also discuss clinical phase transition and overall approval success rates for antibody therapeutics, which are crucial to the biopharmaceutical industry because these rates inform decisions about resource allocation. Our analyses indicate that these molecules have approval success rates in the range of 14-32%, with higher rates associated with antibodies developed for non-cancer indications. Overall, our data suggest that antibody therapeutic development efforts by the biopharmaceutical industry are robust and increasingly successful.

Antibodies to watch in 2023.

In this 14th installment of the annual Antibodies to Watch article series, we discuss key events in commercial monoclonal antibody therapeutics development that occurred in 2022 and forecast events that might occur in 2023. As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevimab (Beyfortus), mirvetuximab soravtansine (ELAHERE™), and teplizumab (TZIELD)), including 4 bispecific antibodies and 1 ADC. Based on FDA action dates, several additional product candidates could be approved by the end of 2022. An additional seven were first approved in China or Japan in 2022, including two bispecific antibodies (cadonilimab and ozoralizumab). Globally, at least 24 investigational antibody therapeutics are undergoing review by regulatory agencies as of mid-November 2022. Our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline grew by ~20% in the past year to include nearly 140 investigational antibody therapeutics that were designed using a wide variety of formats and engineering techniques. Of those in late-stage development, marketing application submissions for at least 23 may occur by the end of 2023, of which 5 are bispecific (odronextamab, erfonrilimab, linvoseltamab, zanidatamab, and talquetamab) and 2 are ADCs (datopotamab deruxtecan, and tusamitamab ravtansine).

Antibody-drug conjugates come of age in oncology.

Antibody-drug conjugates (ADCs) combine the specificity of monoclonal antibodies with the potency of highly cytotoxic agents, potentially reducing the severity of side effects by preferentially targeting their payload to the tumour site. ADCs are being increasingly used in combination with other agents, including as first-line cancer therapies. As the technology to produce these complex therapeutics has matured, many more ADCs have been approved or are in late-phase clinical trials. The diversification of antigenic targets as well as bioactive payloads is rapidly broadening the scope of tumour indications for ADCs. Moreover, novel vector protein formats as well as warheads targeting the tumour microenvironment are expected to improve the intratumour distribution or activation of ADCs, and consequently their anticancer activity for difficult-to-treat tumour types. However, toxicity remains a key issue in the development of these agents, and better understanding and management of ADC-related toxicities will be essential for further optimization. This Review provides a broad overview of the recent advances and challenges in ADC development for cancer treatment.

Antibodies to watch in 2022.

In this 13th annual installment of the annual 'Antibodies to Watch' article series, we discuss key events in commercial antibody therapeutics development that occurred in 2021 and forecast events that might occur in 2022. Regulatory review of antibody therapeutics that target the SARS-CoV-2 coronavirus proceeded at an unprecedented pace in 2021, resulting in both emergency use authorizations and full approvals for sotrovimab, regdanvimab, REGEN-COV2, as well as others, in numerous countries. As of November 1, a total of 11 antibody therapeutics had been granted first approvals in either the United States or European Union in 2021 (evinacumab, dostarlimab loncastuximab tesirine, amivantamab, aducanumab, tralokinumab, anifrolumab, bimekizumab, tisotumab vedotin, regdanvimab, REGEN-COV2). The first global approvals of seven products, however, were granted elsewhere, including Japan (pabinafusp alfa), China (disitamab vedotin, penpulimab, zimberelimab), Australia (sotrovimab, REGEN-COV2), or the Republic of Korea (regdanvimab). Globally, at least 27 novel antibody therapeutics are undergoing review by regulatory agencies. First actions by the Food and Drug Administration on the biologics license applications for faricimab, sutimlimab, tebentafusp, relatlimab, sintilimab, ublituximab and tezepelumab are expected in the first quarter of 2022. Finally, our data show that, with antibodies for COVID-19 excluded, the late-stage commercial clinical pipeline of antibody therapeutics grew by over 30% in the past year. Of those in late-stage development, marketing applications for at least 22 may occur by the end of 2022.

Antibodies to watch in 2021.

In this 12th annual installment of the Antibodies to Watch article series, we discuss key events in antibody therapeutics development that occurred in 2020 and forecast events that might occur in 2021. The coronavirus disease 2019 (COVID-19) pandemic posed an array of challenges and opportunities to the healthcare system in 2020, and it will continue to do so in 2021. Remarkably, by late November 2020, two anti-SARS-CoV antibody products, bamlanivimab and the casirivimab and imdevimab cocktail, were authorized for emergency use by the US Food and Drug Administration (FDA) and the repurposed antibodies levilimab and itolizumab had been registered for emergency use as treatments for COVID-19 in Russia and India, respectively. Despite the pandemic, 10 antibody therapeutics had been granted the first approval in the US or EU in 2020, as of November, and 2 more (tanezumab and margetuximab) may be granted approvals in December 2020.* In addition, prolgolimab and olokizumab had been granted first approvals in Russia and cetuximab saratolacan sodium was first approved in Japan. The number of approvals in 2021 may set a record, as marketing applications for 16 investigational antibody therapeutics are already undergoing regulatory review by either the FDA or the European Medicines Agency. Of these 16 mAbs, 11 are possible treatments for non-cancer indications and 5 are potential treatments for cancer. Based on the information publicly available as of November 2020, 44 antibody therapeutics are in late-stage clinical studies for non-cancer indications, including 6 for COVID-19, and marketing applications for at least 6 (leronlimab, tezepelumab, faricimab, ligelizumab, garetosmab, and fasinumab) are planned in 2021. In addition, 44 antibody therapeutics are in late-stage clinical studies for cancer indications. Of these 44, marketing application submissions for 13 may be submitted by the end of 2021. *Note added in proof on key events announced during December 1-21, 2020: margetuximab-cmkb and ansuvimab-zykl were approved by FDA on December 16 and 21, 2020, respectively; biologics license applications were submitted for ublituximab and amivantamab.

Development trends for monoclonal antibody cancer therapeutics.

Monoclonal antibodies are now established as a key therapeutic modality for a range of diseases. Owing to the ability of these agents to selectively target tumour cells, cancer has been a major focus of development programmes for monoclonal antibodies so far. Here, we overview trends in the clinical development and regulatory approval of monoclonal antibodies for cancer since 1980, with the aim of informing future research and development for this class of therapeutics.

Antibodies to watch in 2020.

This 2020 installment of the annual 'Antibodies to Watch' series documents the antibody therapeutics approved in 2019 and in regulatory review in the United States or European Union, as well as those in late-stage clinical studies, as of November 2019*. At this time, a total of 5 novel antibody therapeutics (romosozumab, risankizumab, polatuzumab vedotin, brolucizumab, and crizanlizumab) had been granted a first approval in either the US or EU, and marketing applications for 13 novel antibody therapeutics (eptinezumab, teprotumumab, enfortumab vedotin, isatuximab, [fam-]trastuzumab deruxtecan, inebilizumab, leronlimab, sacituzumab govitecan, satralizumab, narsoplimab, tafasitamab, REGNEB3 and naxituximab) were undergoing review in these regions, which represent the major markets for antibody therapeutics. Also as of November 2019, 79 novel antibodies were undergoing evaluation in late-stage clinical studies. Of the 79 antibodies, 39 were undergoing evaluation in late-stage studies for non-cancer indications, with 2 of these (ublituximab, pamrevlumab) also in late-stage studies for cancer indications. Companies developing 7 (tanezumab, aducanumab, evinacumab, etrolizumab, sutimlimab, anifrolumab, and teplizumab) of the 39 drugs have indicated that they may submit a marketing application in either the US or EU in 2020. Of the 79 antibodies in late-stage studies, 40 were undergoing evaluation as treatments for cancer, and potentially 9 of these (belantamab mafodotin, oportuzumab monatox, margetuximab, dostarlimab, spartalizumab, 131I-omburtamab, loncastuximab tesirine, balstilimab, and zalifrelimab) may enter regulatory review in late 2019 or in 2020. Overall, the biopharmaceutical industry's clinical pipeline of antibody therapeutics is robust, and should provide a continuous supply of innovative products for patients in the future. *Note on key updates through December 18, 2019: 1) the US Food and Drug Administration granted accelerated approval to enfortumab vedotin-ejfv (Padcev) on December 18, 2019, bringing the total number of novel antibody therapeutics granted a first approval in either the US or EU during 2019 to 6; 2) the European Commission approved romosozumab on December 9, 2019; 3) the European Medicines Agency issued a positive opinion for brolucizumab; 4) Sesen Bio initiated a rolling biologics license application (BLA) on December 6, 2019; 5) GlaxoSmithKline submitted a BLA for belantamab mafodotin; and 6) the status of the Phase 3 study (NCT04128696) of GSK3359609, a humanized IgG4 anti-ICOS antibody, in patients with head and neck squamous cell carcinoma was updated to recruiting from not yet recruiting.

COVID-19 antibody therapeutics tracker: a global online database of antibody therapeutics for the prevention and treatment of COVID-19.

Facing the COVID-19 global healthcare crisis, scientists worldwide are collaborating to develop prophylactic and therapeutic interventions against the disease. Antibody therapeutics hold enormous promise for the treatment of COVID-19. In March 2020, the Chinese Antibody Society, in collaboration with The Antibody Society, initiated the "COVID-19 Antibody Therapeutics Tracker" ("Tracker") (https://chineseantibody.org/covid-19-track/) program to track the antibody-based COVID-19 interventions in preclinical and clinical development globally. The data are collected from the public domain and verified by volunteers on an ongoing basis. Here, we present exploratory data analyses and visualization to demonstrate the latest trends of COVID-19 antibody development, based on data for over 150 research and development programs and molecules included in the "Tracker" as of 8 August 2020. We categorized the data mainly by their targets, formats, development status, developers and country of origin. Although details are limited in some cases, all of the anti-SARS-CoV-2 antibody candidates appear to target the viral spike protein (S protein), and most are full-length monoclonal antibodies. Most of the current COVID-19 antibody therapeutic candidates in clinical trials are repurposed drugs aimed at targets other than virus-specific proteins, while most of these virus-specific therapeutic antibodies are in discovery or preclinical studies. As of 8 August 2020, eight antibody candidates targeting the SARS-CoV-2 S protein have entered clinical studies, including LY-CoV555, REGN-COV2, JS016, TY027, CT-P59, BRII-196, BRII-198 and SCTA01. Ongoing clinical trials of SARS-CoV-2 neutralizing antibodies will help define the utility of these antibodies as a new class of therapeutics for treating COVID-19 and future coronavirus infections.

Finding value in the U.S. Food and Drug Administration's Fast Track program.

The U.S. Food and Drug Administration's (FDA) Fast Track program, created in 1997, was designed to facilitate the development and expedite the review of drugs and biologics intended to treat serious or life-threatening conditions, and that demonstrate the potential to address unmet medical needs. Although the intent is laudable, the significance of designations and effectiveness of the program have recently come into question. Tufts Center for the Study of Drug Development has collected data on fast track candidates since 1998. We analyzed the current dataset of 344 fast track candidates granted nearly 400 designations, representing approximately 70% of the fast track designations granted by FDA, to address questions regarding common metrics. We found that fast track candidates were widely diverse in characteristics and development histories. The complexity and limitations of the data introduced biases in metrics such as clinical phase lengths and phase transition probabilities, although these could be determined for subsets of the candidates. Our results suggest that evaluation of the Fast Track program requires a nuanced approach, and estimates of the program's value should include assessment of the resulting marketed products.

Anti-infective monoclonal antibodies: perils and promise of development.

So far, most monoclonal antibodies have been developed for treating cancer or immunological diseases. However, the global spread of infections such as West Nile and corona viruses, and the need to address the potential threat of bioterrorism, has boosted public interest in, and government support of, counter-measures for infectious diseases. The attractive features of monoclonal antibodies, such as high specificity and effective recruitment of the immune system, would seem to make them excellent candidates as anti-infective agents. Here, we analyse trends in the development and approval of anti-infective monoclonal antibodies, and discuss factors that influence their success.

Antibodies to watch in 2019.

For the past 10 years, the annual 'Antibodies to watch' articles have provided updates on key events in the late-stage development of antibody therapeutics, such as first regulatory review or approval, that occurred in the year before publication or were anticipated to occur during the year of publication. To commemorate the 10th anniversary of the article series and to celebrate the 2018 Nobel Prizes in Chemistry and in Physiology or Medicine, which were given for work that is highly relevant to antibody therapeutics research and development, we expanded the scope of the data presented to include an overview of all commercial clinical development of antibody therapeutics and approval success rates for this class of molecules. Our data indicate that: 1) antibody therapeutics are entering clinical study, and being approved, in record numbers; 2) the commercial pipeline is robust, with over 570 antibody therapeutics at various clinical phases, including 62 in late-stage clinical studies; and 3) Phase 1 to approval success rates are favorable, ranging from 17-25%, depending on the therapeutic area (cancer vs. non-cancer). In 2018, a record number (12) of antibodies (erenumab (Aimovig), fremanezumab (Ajovy), galcanezumab (Emgality), burosumab (Crysvita), lanadelumab (Takhzyro), caplacizumab (Cablivi), mogamulizumab (Poteligeo), moxetumomab pasudodox (Lumoxiti), cemiplimab (Libtayo), ibalizumab (Trogarzo), tildrakizumab (Ilumetri, Ilumya), emapalumab (Gamifant)) that treat a wide variety of diseases were granted a first approval in either the European Union (EU) or United States (US). As of November 2018, 4 antibody therapeutics (sacituzumab govitecan, ravulizumab, risankizumab, romosozumab) were being considered for their first marketing approval in the EU or US, and an additional 3 antibody therapeutics developed by Chinese companies (tislelizumab, sintilimab, camrelizumab) were in regulatory review in China. In addition, our data show that 3 product candidates (leronlimab, brolucizumab, polatuzumab vedotin) may enter regulatory review by the end of 2018, and at least 12 (eptinezumab, teprotumumab, crizanlizumab, satralizumab, tanezumab, isatuximab, spartalizumab, MOR208, oportuzumab monatox, TSR-042, enfortumab vedotin, ublituximab) may enter regulatory review in 2019. Finally, we found that approximately half (18 of 33) of the late-stage pipeline of antibody therapeutics for cancer are immune checkpoint modulators or antibody-drug conjugates. Of these, 7 (tremelimumab, spartalizumab, BCD-100, omburtamab, mirvetuximab soravtansine, trastuzumab duocarmazine, and depatuxizumab mafodotin) are being evaluated in clinical studies with primary completion dates in late 2018 and in 2019, and are thus 'antibodies to watch'. We look forward to documenting progress made with these and other 'antibodies to watch' in the next installment of this article series.

Bispecific antibodies: a mechanistic review of the pipeline.

The term bispecific antibody (bsAb) is used to describe a large family of molecules designed to recognize two different epitopes or antigens. BsAbs come in many formats, ranging from relatively small proteins, merely consisting of two linked antigen-binding fragments, to large immunoglobulin G (IgG)-like molecules with additional domains attached. An attractive bsAb feature is their potential for novel functionalities - that is, activities that do not exist in mixtures of the parental or reference antibodies. In these so-called obligate bsAbs, the physical linkage of the two binding specificities creates a dependency that can be temporal, with binding events occurring sequentially, or spatial, with binding events occurring simultaneously, such as in linking an effector to a target cell. To date, more than 20 different commercialized technology platforms are available for bsAb creation and development, 2 bsAbs are marketed and over 85 are in clinical development. Here, we review the current bsAb landscape from a mechanistic perspective, including a comprehensive overview of the pipeline.

Development trends for new cancer therapeutics and vaccines.

Global commercial development of cancer treatments has dramatically increased over the past 15 years. To assess trends in the process, we analyzed data for 1111 candidates that entered clinical study during 1990-2006. Our results show that although the average number of therapeutic candidates entering clinical study per year more than doubled, the US approval success rate was low (8%) during the period. The therapeutics took seven years on average to go through the clinical and US approval phases, but cancer vaccines have yet to gain any US approvals. These results indicate that improvement in the efficiency of the development process for innovative cancer treatments is needed.

Monoclonal antibody successes in the clinic.

Most monoclonal antibodies in clinical trials are owned by small biotech companies. But with blockbuster-sized revenues and approval rates higher than those for small-molecule drugs, that all may be set to change.

Antibodies to watch in 2018.

The pace of antibody therapeutics development accelerated in 2017, and this faster pace is projected to continue through 2018. Notably, the annual number of antibody therapeutics granted a first approval in either the European Union (EU) or United States (US) reached double-digits (total of 10) for the first time in 2017. The 10 antibodies granted approvals are: brodalumab, dupilumab, sarilumab, guselkumab, benralizumab, ocrelizumab, inotuzumab ozogamicin, avelumab, duvalumab, and emicizumab. Brodalumab, however, had already been approved in Japan in 2016. As of December 1, 2017, nine antibody therapeutics (ibalizumab, burosumab, tildrakizumab, caplacizumab, erenumab, fremanezumab, galcanezumab, romosozumab, mogamulizumab) were in regulatory review in the EU or US, and regulatory actions on their marketing applications are expected by the end of 2018. Based on company announcements and estimated clinical study primary completion dates, and assuming the study results are positive, marketing applications for at least 12 antibody therapeutics that are now being evaluated in late-stage clinical studies may be submitted by the end of 2018. Of the 12 candidates, 8 are for non-cancer indications (lanadelumab, crizanlizumab, ravulizumab, eptinezumab, risankizumab, satralizumab, brolucizumab, PRO140) and 4 are for cancer (sacituzumab govitecan, moxetumomab pasudotox, cemiplimab, ublituximab). Additional antibody therapeutics to watch in 2018 include 19 mAbs undergoing evaluation in late-stage studies with primary completion dates in late 2017 or during 2018. Of these mAbs, 9 are for non-cancer indications (lampalizumab, roledumab, emapalumab, fasinumab, tanezumab, etrolizumab, NEOD001, gantenerumab, anifrolumab) and 10 are for cancer indications (tremelimumab, isatuximab, BCD-100, carotuximab, camrelizumab, IBI308, glembatumumab vedotin, mirvetuximab soravtansine, oportuzumab monatox, L19IL2/L19TNF). Positive clinical study results may enable marketing application submissions in 2018. Brief summaries of these antibody therapeutics are provided in this installment of the 'Antibodies to watch' article series.

Trends in the development and approval of monoclonal antibodies for viral infections.

Monoclonal antibodies (mAbs) developed for either the prevention or treatment of viral diseases represent a small, but valuable, class of products. Since 1985, commercial firms have initiated clinical studies involving a total of 28 mAbs. To date, one product (palivizumab) has been approved and eight candidates are currently in clinical study. Most commercial mAbs studied as antiviral agents in the clinic have either directly or indirectly targeted human immunodeficiency virus, respiratory syncytial virus, or hepatitis C virus infections. However, the ability of mAbs to bind to specific targets and utilize various anti-infective modes of action would seem to make them well suited for the prevention and/or treatment of a wider variety of viral diseases. A number of factors, including the continuing need for innovative medicines for viral infections, the global spread of viral infections, and increased government funding for the study of pathogen countermeasures, have prompted companies to reconsider mAbs as antiviral agents. Public sector research into the use of mAbs against emerging pathogens, such as severe acute respiratory syndrome coronavirus, may have already provided candidates for further development.

Trends in development and approval times for new therapeutics in the United States.

The process of clinical development and regulatory review of new therapeutics in the United States was significantly changed by a number of legislative acts passed in the 1980s and 1990s. These acts were designed to encourage the development of innovative products, especially for rare, serious or life-threatening diseases, and to ensure that patients had timely access to these treatments. To assess the effects of the various modifications to the process, the Tufts Center for the Study of Drug Development analysed clinical development and approval data for 554 therapeutics (504 small molecules, 40 recombinant proteins and 10 monoclonal antibodies) approved in the United States from 1980-2001. Trends in the number of approved products and the clinical development and approval times indicated that the effects of these changes were generally beneficial as of the mid- to late-1990s, but that the gains have not been sustained in the early 2000s. Current efforts by the FDA, and the pharmaceutical and biopharmaceutical industry, to reverse the recent tendency toward fewer new approvals and longer approval times are discussed.

Antibodies to watch in 2017.

Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US. Brodalumab, was granted a first approval in Japan in July 2016. Regulatory actions on marketing applications for brodalumab in the EU and US are not expected until 2017. In 2017, first EU or US approvals may also be granted for at least nine mAbs (ocrelizumab, avelumab, Xilonix, inotuzumab ozogamicin, dupilumab, sirukumab, sarilumab, guselkumab, romosozumab) that are not yet approved in any country. Based on announcements of company plans for regulatory submissions and the estimated completion dates for late-stage clinical studies, and assuming the study results are positive, marketing applications for at least 6 antibody therapeutics (benralizumab, tildrakizumab, emicizumab, galcanezumab, ibalizumab, PRO-140) that are now being evaluated in late-stage clinical studies may be submitted during December 2016* or 2017. Other 'antibodies to watch' in 2017 include 20 mAbs are undergoing evaluation in pivotal studies that have estimated primary completion dates in late 2016 or during 2017. Of these, 5 mAbs are for cancer (durvalumab, JNJ-56022473, ublituximab, anetumab ravtansine, glembatumumab vedotin) and 15 mAbs are for non-cancer indications (caplacizumab, lanadelumab, roledumab, tralokinumab, risankizumab, SA237, emapalumab, suptavumab, erenumab, eptinezumab, fremanezumab, fasinumab, tanezumab, lampalizumab, brolucizumab). Positive results from these studies may enable submission of marketing applications in 2017 or 2018, or provide justification for additional studies. *See note added in proof for update through December 31, 2016.

Trends in US approvals: new biopharmaceuticals and vaccines.

The efficient development and approval of new therapeutics and vaccines is vital to the health and welfare of patients. Tufts Center for the Study of Drug Development has collected and analyzed data for new protein therapeutics and vaccines approved in the USA during the past decade. Our results suggest trends toward longer clinical and approval phases for the therapeutics, particularly for oncology products. In this Opinion article, we discuss various legislative acts and FDA initiatives that might improve the efficiency of drug development and approval. Furthermore, few new vaccines have been approved in the past 10 years owing, at least in part, to the lack of incentives for the development of the products. We predict that this might change in the future as government and industry respond to the twin threats of the global spread of infectious diseases and potential bioterrorism.