DRUDIS 1582 1–4 Drug Discovery Today Volume 00, Number 00 February 2015
PERSPECTIVE
feature An analysis of FDA-approved drugs for inflammation and autoimmune diseases The term ‘inflammation’ captures a variety of disease processes linked with the immune system. An analysis of US Food and Drug Administration (FDA)-approved nuclear molecular entities (NMEs) reveals notable trends in terms of acute and chronic inflammatory indications. The number of NMEs peaked during the 1990s and has since declined by more than 50%. Whereas pharmaceutical companies have dominated the field, biotechnology companies now receive half of new approvals and academia has a relatively large role in terms of pivotal first patents. Another notable trend is that the relative number of NMEs targeting allergy has been decreasing, whereas those targeting autoimmune indications is increasing. Unlike other indications, NMEs for inflammation tend towards nuclear receptors and cytokines, and a disproportionate number of biologics target cytokine pathways.
Introduction Q2 Diseases of the immune and repair systems of
the body comprise a vast array of maladies. Whereas inflammation has been shown to contribute to many indications, ranging from heart disease through to cancer, we focused our analysis reported here on the development of NMEs that directly target acute or chronic inflammation. For example, although aspirin (approved in 1899) is now renown for its antiinflammatory properties, its initial approval was for pain analgesia and, thus, is not included in the analyses herein. The first FDA-approved drug targeting an inflammatory indication, desoxycorticosterone (DOCA), was approved in 1939 for the treatment of Addison’s disease. This form of adrenal insufficiency, first described in 1849, is most
1359-6446/ß 2015 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.drudis.2015.02.006
commonly caused by autoimmune destruction of the adrenal cortex [1,2]. Although rare, Addison’s disease has been popularized in part by its potential links with John F. Kennedy and has also been implicated retrospectively to historical figures ranging from Jane Austen to Osama bin Laden, although both postmortem diagnoses are contentious [3–6]. DOCA itself is notable in that it not only functions to replace hormones lost as a result of this destruction, but also is a steroidal regulator of inflammation and autoimmunity, and has been more widely utilized in this capacity than as hormone replacement [7]. A total of 168 NMEs have received approval from the FDA, with initial indications involving the treatment or prevention of acute or chronic inflammation, including autoimmunity (Fig. 1a).
When evaluated on a decade-by-decade basis, the average number of approvals increased from the 1940s through to the 1990s, declining thereafter (Fig. 1b). In the current decade, the average number of NMEs stands at two per year. In the course of evaluating the sources of innovation for the NMEs, we noted changes in the relative contributions from the pharmaceutical, biotechnology, and academic sectors that are relatively unique to inflammatory diseases and had not been observed previously. To be consistent throughout our ongoing series of articles on FDA-approved drugs, we define herein biotechnology organizations as those founded coincident or after Cetus in 1971 (see [8] for the rationale behind this definition), with the pharmaceutical designation applied to companies formed before the 1970s. Although
www.drugdiscoverytoday.com 1 Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
Features PERSPECTIVE
Q1 Michael S. Kinch, [email protected] and Janie Merkel
DRUDIS 1582 1–4 PERSPECTIVE
Drug Discovery Today Volume 00, Number 00 February 2015
(a) 180
(b) 5 AverageannualNME
CumulativeNMEs
160 140 120 100 80 60 40
4 3 2 1
20 0 1940
0 1960
1980 Year
2000
1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s Decade
80%
80% Patentassignee
(d) 100%
NMEawardee
(c) 100%
60% 40% 20%
60% 40% 20%
0%
0% 1980s
1990s 2000s Decade
2010s
1980s
1990s 2000s Decade
2010s
Drug Discovery Today
FIGURE 1
Overview of new molecular entity (NME) approvals for inflammation. (a) The cumulative number of NMEs approved by the US Food and Drug Administration (FDA) for human use in the USA over time. (b) The average annual rate of NME approvals was determined on a decade-by-decade basis, revealing a peak during the 1990s. The relative proportion of pharmaceutical (red), biotechnology (blue), and academic (green) organizations receiving the final FDA approval (c) or awarded the first patent (d) is compared over time.
Features PERSPECTIVE
imperfect, these designations revealed that pharmaceutical companies dominated all activities in the research and development of NMEs targeting inflammation, from the inception of the field during the 1930s (data not shown; Fig. 1c). Beginning with the start of the new millennium, biotechnology companies became more prominent in terms of NMEs approved by the FDA (Fig. 1c) and comparable findings were observed when analyzing investigational new drug (IND) submissions and clinical trial participation (data not shown). Academia (defined herein as university and governmental laboratories) has had a larger role in terms of patent submissions in inflammatory diseases. As will be profiled in a later article in this series, academic institutions have consistently contributed to drug research and development, but inflammation stands out for the relative role of academia during early-stage research. For example, one-third of the key first patents for inflammation NMEs in the current decade were filed by academic organizations. This might reflect the growth in understanding of the immune system (which began in earnest during the mid-1950s) and/or an increasing trend towards newer technologies. We also considered that changes in the indications for which an NME is first approved might represent another potential reason for the relatively large role of academia during early-stage 2
(a)
Allergy 28% Autoimmune 37%
Inflammation 15%
Transplant 6%
Asthma 14%
(b) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s
Decade Drug Discovery Today
FIGURE 2
Disease types targeted by new molecular entity (NME) initial approvals (a) The overall and relative number of NMEs targeting each disease type. (b) The relative proportion of NMEs targeting each indication over time, using the same color scheme as in (a).
www.drugdiscoverytoday.com Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
DRUDIS 1582 1–4 Drug Discovery Today Volume 00, Number 00 February 2015
(b) 6% 8%
13% Cytokine 7%
Dehydrogenase GPCR
27%
NuclearReceptor Oxygenase 39%
Average annual NME
(a)
PERSPECTIVE
Other
4
3
2
1
0 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s
Decade (c)
(d)
NMEs per decade
4
Noncytokine 7
3
2
Cytokine 17
1
0 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s
Decade
FIGURE 3
Change in cellular targets and the growth of biologics. (a) The relative proportion of cellular proteins targeted by new molecular entities (NMEs) approved for inflammation is shown, as are changes observed on a decade-by-decade basis, using the same color scheme as in (a,b). (c) The recent growth in biologics (blue) versus small molecules (red) on a decade-by-decade basis. (d) Within biologics, the proportion targeting cytokines or their receptors is indicated.
discovery (manifested as patent assignees). An analysis of the clinical indications for each approval revealed that the 63 NMEs targeting autoimmune diseases represent more than onethird of all inflammation approvals, followed by allergy (47; 28%), asthma (24; 14%), general inflammation (23; 14%), and transplantation medicines (10; 6%) (Fig. 2a). The emergence of autoimmune diseases is relatively recent. Whereas allergy indications dominated the first decades of modern drug development, NMEs targeting these indications have retreated, whereas autoimmune indications now dominate the field (Fig. 2b). The changes in indications also reflect a dynamic nature in molecular targeting. Similar to most other major categories of indications, G-protein-coupled receptors (GPCRs) are the largest source of cellular targets for inflammatory diseases, encompassing almost two of five NMEs. Inflammatory diseases stand out for a relative abundance of nuclear receptor (27%) and cytokine (13%) targets. Unsurprisingly, the nuclear receptor targets largely encompass
corticosteroid receptors, through which small molecule mimics of glucocorticoid agonists increase anti-inflammatory gene expression changes. By contrast, cytokine targets stood out in part because they are disproportionately targeted by biologics in general and monoclonal antibodies in particular. The past three decades have witnessed a rise in biologics-based medicines, with an annual average of one NME targeting inflammatory disease (Fig. 3c). Notably, a disproportionate number of biologics (17 of 24; 71%) target cytokines or their receptors (Fig. 3d).
Concluding remarks: findings and implications The major finding of the present study focused on inflammation and autoimmune disease is that progress towards the development of new medicines has been particularly dynamic since the birth of the modern biopharmaceutical industry during the 1930s. Notable changes include evidence that the average annual rate of NME introduction now stands at a level that is less than half of its peak during the 1990s and at
a level seen previously during the 1970s. Another interesting observation is that the types of indication targeted have progressively moved away from allergy and general inflammation and towards indications linked to autoimmunity. These changes reflect a transition in the types of molecular target, which were dominated by two types of cellular protein (GPCRs and steroid receptors) from the inception of the field until the past two decades. Recent approvals encompass new types of target and coincide in part with the rise of biotechnology in general and in biologics-based therapies in particular. With regard to biologics, a disproportionate fraction target cytokine pathways. Although the overall rate of new FDA approvals peaked during the 1990s and is currently less than approximately 10% from that peak [9], the negative trend in inflammationbased NMEs (a drop of 53%) is particularly prominent. The magnitude of the decrease is particularly puzzling given the dramatic rise in knowledge of the immune system over the past few decades. One possibility is that the relative
www.drugdiscoverytoday.com 3 Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
Features PERSPECTIVE
Drug Discovery Today
DRUDIS 1582 1–4 PERSPECTIVE
burst of approvals appropriately reflects the burst in fundamental knowledge of the immune system that started during the late 1950s (following the clonal selection theory and the discovery of human leukocyte antigens). Alternatively, the clearance of the proverbial ‘low-hanging fruit’ could be invoked. A third possibility is that the expertise that led to the peak approval rate of the 1990s has been deployed elsewhere. For example, and as cited in an earlier paper in this series [10], the recent increase in the number of NMEs targeting cancer largely encompasses immune cell targets (e.g. leukemia and/or lymphoma) and immunologically based therapies (e.g. monoclonal antibodies). Indeed, many NMEs originally approved for oncology were subsequently approved, or prescribed off-label, for autoimmune indications. A prominent example of this practice is the use of rituximab in rheumatoid arthritis (where it is licensed) and in multiple sclerosis, lupus, and other autoimmune indications (where it is used off-patent) [11–13]. Given the more lucrative pricing associated with oncology drugs [14], it seems likely that the decreased rate of NME
Drug Discovery Today Volume 00, Number 00 February 2015
approvals for inflammation is not as dramatic as Fig. 1 might indicate.
Acknowledgments This work was conducted as part of a project at the Yale Center for Molecular Discovery (ycmd.yale.edu) to develop a collection of all FDA-approved small molecules as a resource for screening to emphasize drug repurposing. Please contact the authors if you or your organization would be interested in potential participation in this project. References 1 Ten, S. et al. (2001) Addison’s disease 2001. J. Clin. Endocrinol. Metabol. 86, 2909–2922 2 Pearce, J.M. (2004) Thomas Addison (1793–1860). J. R. Soc. Med. 97, 297–300 3 Hoenig, L.J. and Burgdorf, W.H. (2013) President Kennedy’s White House tan. JAMA Dermatol. 149, 597 4 White, K.G. (2009) Jane Austen and Addison’s disease: an unconvincing diagnosis. Med. Hum. 35, 98–100 5 Cope, Z. (1964) Jane Austen’s last illness. Br. Med. J. 2, 182–183 6 Wright, L. (2006) The Looming Tower. Knopf Doubleday 7 Biglieri, E.G. (1995) My engagement with steroids: a review. Steroids 60, 52–58
8 Kinch, M.S. (2014) The rise (and decline?) of biotechnology. Drug Discov. Today 19, 1686–1690 9 Kinch, M.S. et al. (2014) An overview of FDA-approved new molecular entities: 1827–2013. Drug Discov. Today 19, 1033–1039 10 Kinch, M.S. (2014) An analysis of FDA-approved drugs for oncology. Drug Discov. Today 19, 1831–1835 11 Edwards, J.C.W. et al. (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572–2581 12 Silverman, G.J. and Weisman, S. (2003) Rituximab therapy and autoimmune disorders: prospects for antiB cell therapy. Arthritis Rheum. 48, 1484–1492 13 Abdulla, N.E. et al. (2012) Rituximab: current status as therapy for malignant and benign hematologic disorders. BioDrugs 26, 71–82 14 Abraham, J. (2013) Developing oncology biosimilars: an essential approach for the future. Semin. Oncol. 40 (Suppl. 1), S5–S24
Michael S. Kinch, Janie Merkel Yale Center for Molecular Discovery, Yale University, West Haven, CT 06516, USA
Features PERSPECTIVE 4
www.drugdiscoverytoday.com Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
PERSPECTIVE
feature An analysis of FDA-approved drugs for inflammation and autoimmune diseases The term ‘inflammation’ captures a variety of disease processes linked with the immune system. An analysis of US Food and Drug Administration (FDA)-approved nuclear molecular entities (NMEs) reveals notable trends in terms of acute and chronic inflammatory indications. The number of NMEs peaked during the 1990s and has since declined by more than 50%. Whereas pharmaceutical companies have dominated the field, biotechnology companies now receive half of new approvals and academia has a relatively large role in terms of pivotal first patents. Another notable trend is that the relative number of NMEs targeting allergy has been decreasing, whereas those targeting autoimmune indications is increasing. Unlike other indications, NMEs for inflammation tend towards nuclear receptors and cytokines, and a disproportionate number of biologics target cytokine pathways.
Introduction Q2 Diseases of the immune and repair systems of
the body comprise a vast array of maladies. Whereas inflammation has been shown to contribute to many indications, ranging from heart disease through to cancer, we focused our analysis reported here on the development of NMEs that directly target acute or chronic inflammation. For example, although aspirin (approved in 1899) is now renown for its antiinflammatory properties, its initial approval was for pain analgesia and, thus, is not included in the analyses herein. The first FDA-approved drug targeting an inflammatory indication, desoxycorticosterone (DOCA), was approved in 1939 for the treatment of Addison’s disease. This form of adrenal insufficiency, first described in 1849, is most
1359-6446/ß 2015 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.drudis.2015.02.006
commonly caused by autoimmune destruction of the adrenal cortex [1,2]. Although rare, Addison’s disease has been popularized in part by its potential links with John F. Kennedy and has also been implicated retrospectively to historical figures ranging from Jane Austen to Osama bin Laden, although both postmortem diagnoses are contentious [3–6]. DOCA itself is notable in that it not only functions to replace hormones lost as a result of this destruction, but also is a steroidal regulator of inflammation and autoimmunity, and has been more widely utilized in this capacity than as hormone replacement [7]. A total of 168 NMEs have received approval from the FDA, with initial indications involving the treatment or prevention of acute or chronic inflammation, including autoimmunity (Fig. 1a).
When evaluated on a decade-by-decade basis, the average number of approvals increased from the 1940s through to the 1990s, declining thereafter (Fig. 1b). In the current decade, the average number of NMEs stands at two per year. In the course of evaluating the sources of innovation for the NMEs, we noted changes in the relative contributions from the pharmaceutical, biotechnology, and academic sectors that are relatively unique to inflammatory diseases and had not been observed previously. To be consistent throughout our ongoing series of articles on FDA-approved drugs, we define herein biotechnology organizations as those founded coincident or after Cetus in 1971 (see [8] for the rationale behind this definition), with the pharmaceutical designation applied to companies formed before the 1970s. Although
www.drugdiscoverytoday.com 1 Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
Features PERSPECTIVE
Q1 Michael S. Kinch, [email protected] and Janie Merkel
DRUDIS 1582 1–4 PERSPECTIVE
Drug Discovery Today Volume 00, Number 00 February 2015
(a) 180
(b) 5 AverageannualNME
CumulativeNMEs
160 140 120 100 80 60 40
4 3 2 1
20 0 1940
0 1960
1980 Year
2000
1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s Decade
80%
80% Patentassignee
(d) 100%
NMEawardee
(c) 100%
60% 40% 20%
60% 40% 20%
0%
0% 1980s
1990s 2000s Decade
2010s
1980s
1990s 2000s Decade
2010s
Drug Discovery Today
FIGURE 1
Overview of new molecular entity (NME) approvals for inflammation. (a) The cumulative number of NMEs approved by the US Food and Drug Administration (FDA) for human use in the USA over time. (b) The average annual rate of NME approvals was determined on a decade-by-decade basis, revealing a peak during the 1990s. The relative proportion of pharmaceutical (red), biotechnology (blue), and academic (green) organizations receiving the final FDA approval (c) or awarded the first patent (d) is compared over time.
Features PERSPECTIVE
imperfect, these designations revealed that pharmaceutical companies dominated all activities in the research and development of NMEs targeting inflammation, from the inception of the field during the 1930s (data not shown; Fig. 1c). Beginning with the start of the new millennium, biotechnology companies became more prominent in terms of NMEs approved by the FDA (Fig. 1c) and comparable findings were observed when analyzing investigational new drug (IND) submissions and clinical trial participation (data not shown). Academia (defined herein as university and governmental laboratories) has had a larger role in terms of patent submissions in inflammatory diseases. As will be profiled in a later article in this series, academic institutions have consistently contributed to drug research and development, but inflammation stands out for the relative role of academia during early-stage research. For example, one-third of the key first patents for inflammation NMEs in the current decade were filed by academic organizations. This might reflect the growth in understanding of the immune system (which began in earnest during the mid-1950s) and/or an increasing trend towards newer technologies. We also considered that changes in the indications for which an NME is first approved might represent another potential reason for the relatively large role of academia during early-stage 2
(a)
Allergy 28% Autoimmune 37%
Inflammation 15%
Transplant 6%
Asthma 14%
(b) 100% 90% 80% 70% 60% 50% 40% 30% 20% 10% 0%
1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s
Decade Drug Discovery Today
FIGURE 2
Disease types targeted by new molecular entity (NME) initial approvals (a) The overall and relative number of NMEs targeting each disease type. (b) The relative proportion of NMEs targeting each indication over time, using the same color scheme as in (a).
www.drugdiscoverytoday.com Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
DRUDIS 1582 1–4 Drug Discovery Today Volume 00, Number 00 February 2015
(b) 6% 8%
13% Cytokine 7%
Dehydrogenase GPCR
27%
NuclearReceptor Oxygenase 39%
Average annual NME
(a)
PERSPECTIVE
Other
4
3
2
1
0 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s
Decade (c)
(d)
NMEs per decade
4
Noncytokine 7
3
2
Cytokine 17
1
0 1940s 1950s 1960s 1970s 1980s 1990s 2000s 2010s
Decade
FIGURE 3
Change in cellular targets and the growth of biologics. (a) The relative proportion of cellular proteins targeted by new molecular entities (NMEs) approved for inflammation is shown, as are changes observed on a decade-by-decade basis, using the same color scheme as in (a,b). (c) The recent growth in biologics (blue) versus small molecules (red) on a decade-by-decade basis. (d) Within biologics, the proportion targeting cytokines or their receptors is indicated.
discovery (manifested as patent assignees). An analysis of the clinical indications for each approval revealed that the 63 NMEs targeting autoimmune diseases represent more than onethird of all inflammation approvals, followed by allergy (47; 28%), asthma (24; 14%), general inflammation (23; 14%), and transplantation medicines (10; 6%) (Fig. 2a). The emergence of autoimmune diseases is relatively recent. Whereas allergy indications dominated the first decades of modern drug development, NMEs targeting these indications have retreated, whereas autoimmune indications now dominate the field (Fig. 2b). The changes in indications also reflect a dynamic nature in molecular targeting. Similar to most other major categories of indications, G-protein-coupled receptors (GPCRs) are the largest source of cellular targets for inflammatory diseases, encompassing almost two of five NMEs. Inflammatory diseases stand out for a relative abundance of nuclear receptor (27%) and cytokine (13%) targets. Unsurprisingly, the nuclear receptor targets largely encompass
corticosteroid receptors, through which small molecule mimics of glucocorticoid agonists increase anti-inflammatory gene expression changes. By contrast, cytokine targets stood out in part because they are disproportionately targeted by biologics in general and monoclonal antibodies in particular. The past three decades have witnessed a rise in biologics-based medicines, with an annual average of one NME targeting inflammatory disease (Fig. 3c). Notably, a disproportionate number of biologics (17 of 24; 71%) target cytokines or their receptors (Fig. 3d).
Concluding remarks: findings and implications The major finding of the present study focused on inflammation and autoimmune disease is that progress towards the development of new medicines has been particularly dynamic since the birth of the modern biopharmaceutical industry during the 1930s. Notable changes include evidence that the average annual rate of NME introduction now stands at a level that is less than half of its peak during the 1990s and at
a level seen previously during the 1970s. Another interesting observation is that the types of indication targeted have progressively moved away from allergy and general inflammation and towards indications linked to autoimmunity. These changes reflect a transition in the types of molecular target, which were dominated by two types of cellular protein (GPCRs and steroid receptors) from the inception of the field until the past two decades. Recent approvals encompass new types of target and coincide in part with the rise of biotechnology in general and in biologics-based therapies in particular. With regard to biologics, a disproportionate fraction target cytokine pathways. Although the overall rate of new FDA approvals peaked during the 1990s and is currently less than approximately 10% from that peak [9], the negative trend in inflammationbased NMEs (a drop of 53%) is particularly prominent. The magnitude of the decrease is particularly puzzling given the dramatic rise in knowledge of the immune system over the past few decades. One possibility is that the relative
www.drugdiscoverytoday.com 3 Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
Features PERSPECTIVE
Drug Discovery Today
DRUDIS 1582 1–4 PERSPECTIVE
burst of approvals appropriately reflects the burst in fundamental knowledge of the immune system that started during the late 1950s (following the clonal selection theory and the discovery of human leukocyte antigens). Alternatively, the clearance of the proverbial ‘low-hanging fruit’ could be invoked. A third possibility is that the expertise that led to the peak approval rate of the 1990s has been deployed elsewhere. For example, and as cited in an earlier paper in this series [10], the recent increase in the number of NMEs targeting cancer largely encompasses immune cell targets (e.g. leukemia and/or lymphoma) and immunologically based therapies (e.g. monoclonal antibodies). Indeed, many NMEs originally approved for oncology were subsequently approved, or prescribed off-label, for autoimmune indications. A prominent example of this practice is the use of rituximab in rheumatoid arthritis (where it is licensed) and in multiple sclerosis, lupus, and other autoimmune indications (where it is used off-patent) [11–13]. Given the more lucrative pricing associated with oncology drugs [14], it seems likely that the decreased rate of NME
Drug Discovery Today Volume 00, Number 00 February 2015
approvals for inflammation is not as dramatic as Fig. 1 might indicate.
Acknowledgments This work was conducted as part of a project at the Yale Center for Molecular Discovery (ycmd.yale.edu) to develop a collection of all FDA-approved small molecules as a resource for screening to emphasize drug repurposing. Please contact the authors if you or your organization would be interested in potential participation in this project. References 1 Ten, S. et al. (2001) Addison’s disease 2001. J. Clin. Endocrinol. Metabol. 86, 2909–2922 2 Pearce, J.M. (2004) Thomas Addison (1793–1860). J. R. Soc. Med. 97, 297–300 3 Hoenig, L.J. and Burgdorf, W.H. (2013) President Kennedy’s White House tan. JAMA Dermatol. 149, 597 4 White, K.G. (2009) Jane Austen and Addison’s disease: an unconvincing diagnosis. Med. Hum. 35, 98–100 5 Cope, Z. (1964) Jane Austen’s last illness. Br. Med. J. 2, 182–183 6 Wright, L. (2006) The Looming Tower. Knopf Doubleday 7 Biglieri, E.G. (1995) My engagement with steroids: a review. Steroids 60, 52–58
8 Kinch, M.S. (2014) The rise (and decline?) of biotechnology. Drug Discov. Today 19, 1686–1690 9 Kinch, M.S. et al. (2014) An overview of FDA-approved new molecular entities: 1827–2013. Drug Discov. Today 19, 1033–1039 10 Kinch, M.S. (2014) An analysis of FDA-approved drugs for oncology. Drug Discov. Today 19, 1831–1835 11 Edwards, J.C.W. et al. (2004) Efficacy of B-cell-targeted therapy with rituximab in patients with rheumatoid arthritis. N. Engl. J. Med. 350, 2572–2581 12 Silverman, G.J. and Weisman, S. (2003) Rituximab therapy and autoimmune disorders: prospects for antiB cell therapy. Arthritis Rheum. 48, 1484–1492 13 Abdulla, N.E. et al. (2012) Rituximab: current status as therapy for malignant and benign hematologic disorders. BioDrugs 26, 71–82 14 Abraham, J. (2013) Developing oncology biosimilars: an essential approach for the future. Semin. Oncol. 40 (Suppl. 1), S5–S24
Michael S. Kinch, Janie Merkel Yale Center for Molecular Discovery, Yale University, West Haven, CT 06516, USA
Features PERSPECTIVE 4
www.drugdiscoverytoday.com Please cite this article in press as: Kinch, M.S., Merkel, J. An analysis of FDA-approved drugs for inflammation and autoimmune diseases, Drug Discov Today (2015), http://dx.doi.org/ 10.1016/j.drudis.2015.02.006
