DRUDIS-1424; No of Pages 4 Drug Discovery Today Volume 00, Number 00 June 2014
PERSPECTIVE
feature Trends in pharmaceutical targeting of clinical indications: 1930–2013 Michael S. Kinch, [email protected], [email protected], Janie Merkel and Sheila Umlauf
Introduction Change in the pharmaceutical industry has been constant and dynamic since its inception in the 1930s. Nowhere is this more apparent than in the therapeutic applications of new medicines. As part of a review of new molecular entities (NMEs), we seek to identify the therapeutic indications targeted by newly approved drugs.
Targeting major indications As part of our overall analysis of NMEs approved by the FDA, the details of which can be found in the first article of this series [1], the indications for each of the 1453 NMEs approved from 1930 through to the end of 2013 were assigned to major categories (e.g. oncology, cardiovascular diseases, etc.). Using this approach, 20 groups of indications captured the majority of NME approvals, with at least ten different NMEs in each category. A minority of NMEs were counted in two categories (e.g. an antibiotic for ocular use
would be found in infectious diseases and ophthalmology) (Fig. 1a). Infectious diseases represented the most common set of indications, with 299 NMEs (or more than one in five NMEs approved) targeting microorganisms. Other leading indications include cardiovascular diseases (211 NMEs; 14.5% of all NMEs), oncology (193; 13.3%) and autoimmunity/inflammation (180; 12.4%). These four indications capture 60.8% of all NMEs approved by the FDA. Beyond these four, the number of NMEs drops precipitously, with the next largest five indications (metabolic, neurological, psychiatric diseases, as well as pain/itch and ophthalmology) ranging from 50 to 80 NMEs each. Having established the major indications targeted by NMEs, we asked if and how the types of indications changed from 1930 to the present day (Fig. 1b and c). In the period spanning 1961 through to 1985 more than one-quarter of NMEs was devoted to infectious diseases. Since that
1359-6446/06/$ - see front matter ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2014.05.021
Features PERSPECTIVE
An analysis of FDA-approved new molecular entities (NMEs) reveals trends in therapeutic applications. Four groupings (infectious diseases, cardiovascular diseases, autoimmune/inflammatory diseases and cancer) capture more than 60% of NMEs. Infectious diseases are the most targeted indications. Near the turn of the new millennium, the rate of new approvals for infectious diseases decreased. The absolute and relative number of NMEs targeting psychiatric, neurological and pain/itch indications also declined. By contrast, NMEs targeting cancer have risen in the past two decades as have NMEs targeting orphan indications. These results suggest the drug development community has largely been responsive to public health and market needs. However, finite resources might indicate emphasis on some unmet needs could come at the cost of others.
time, the relative proportion has shrunk to a current level of 15%. This represents a proportional and absolute decrease. At its peak, more than six new drugs targeting infectious diseases were approved annually. As of the first decade in the new century, this decreased to an average of 4.4 NMEs per year. The causes of the decline in emphasis on infectious disease were not assessed in the present study. These could include the rise of vaccines, increased understanding of pathogens and the disease process as well as business trends such as the relative return on investment as perceived by key decision-makers within the biopharmaceutical industry. NMEs devoted to oncology have gained more prominence. Whereas fewer than 5% of new drugs introduced in the 1930s targeted cancer, the fraction today exceeds one-third. In absolute terms, the number of new oncology drugs has increased from less than one approval every five www.drugdiscoverytoday.com
1
DRUDIS-1424; No of Pages 4 PERSPECTIVE
(b)
Nutrition
40%
Urinary
35%
Bleeding
30% NMEs targeting therapeutic class
(a)
Drug Discovery Today Volume 00, Number 00 June 2014
Bone Ulcer Digestive Reproductive Hormonal
Infection Oncology Metabolic
Cardiovascular Immunology
25% 20% 15% 10%
Sleep disorder
5%
Respiratory 0% 1940
Anaesthesia
1960
1980
2000
Opthamology Pain/itch
(c)
15%
Psychiatric NMEs targeting therapeutic class
Neurological Metabolic Autoimune/inflammation Oncology Cardiovascular Infectious diseases 0
50
Neurological Psychiatry Pain/Itch Opthamology Anaesthesia
12% 9% 6% 3% 0% 1940
100 150 200 250 300 Total NMEs
1960
1980
2000 Drug Discovery Today
Features PERSPECTIVE
FIGURE 1
New molecular entity (NME) targeting of indications. (a) The leading 20 therapeutic applications for NMEs are indicated. Note that the leading four indications encompass more than 60% of all NMEs. (b,c) The top ten indications were assessed over time on a decade-by-decade basis.
Indications targeted (1981–2013)
Pharmaceutical Rank (share of portfolio)
Biotechnology Rank (share of portfolio)
Infectious diseases
1 (21%)
2 (18%)
Cardiovascular
2 (16%)
4 (11%)
Oncology
3 (14%)
1 (29%)
Autoimmune/inflammation
3 (14%)
3 (12%)
Metabolic
5
(6%)
5 (9%)
Neurological
6
(6%)
7 (4%)
Psychiatric
7 (5%)
8 (2%)
Pain/itch
9 (3%)
8 (2%)
Ophthalmology
8 (4%)
6 (6%)
Anesthesia
10 (3%)
None Drug Discovery Today
FIGURE 2
Similarities and differences between pharmaceutical and biotechnology companies. Shown are the relative contributions of pharmaceutical and biotechnology industries to the components of the collective leading ten indications (left column). 2
www.drugdiscoverytoday.com
DRUDIS-1424; No of Pages 4 Drug Discovery Today Volume 00, Number 00 June 2014
(b)
12
40% 35%
10
Fraction of orphan NMEs
Average annual orphan NMEs
(a)
PERSPECTIVE
8 6 4 2
30% 25% 20% 15% 10% 5%
0
0% 1980s
1990s
2000s
2010s
(c)
1980s
Orphan NMEs
Orphan fraction
Biotechnology
88
45%
Pharmaceutical
97
14%
1990s
2000s
2010s
Drug Discovery Today
years (in the 1930s and 1940s) to a current annual rate of 11 NMEs. Perhaps the most dramatic changes are seen with NMEs targeting pain/itch and anesthesia. One in ten drugs targeted these indications in the early years of the pharmaceutical industry. By contrast, the current decade has not yet witnessed a new approval in either indication. NMEs targeting psychiatric indications also peaked in the 1960s but new entries have decreased by 75%. With the exception of psychiatric drugs, many shifts began in the 1980s. This timeframe is coincident with the rise of biotechnology. Thus, we compared indications targeted by conventional pharmaceutical and biotechnology companies (Fig. 2). For the purpose of this analysis, we broadly designate organizations founded before 1971 as pharmaceutical and those after 1971 as biotechnology companies, please see an earlier paper in the series for a discussion of the imperfect definition of biotechnology [2]. We then analyzed all drugs approved during or after 1981 (the first year that a biotechnology company had actively contributed to an NME).
Whereas four indications (infectious, cardiovascular, immunological diseases and cancer) capture two-thirds of all NME approvals for pharmaceutical and biotechnology companies, the portfolios of biotechnology companies placed twice as much emphasis on oncology products as their pharmaceutical peers (29% vs 14%, respectively). Thus, the rise of biotechnology coincides with the increase in oncology approvals over the past three decades. By contrast, biotechnology companies were underrepresented for drugs targeting cardiovascular, psychiatric and/or anesthesia applications.
Rise of orphan indications The Orphan Drug Act (ODA), passed in January 1983 [3], provided marketing and tax incentives for companies that develop drugs targeting disorders that affect fewer than 200 000 people in the USA. Thus, we asked if the ODA impacted drug development and how the two industries responded to these changes. These analyses focused on NMEs where the initial approval qualified as an orphan indication (excluding approved drugs that were subsequently approved for use in orphan diseases).
In the time period immediately following approval of the ODA in 1983, an average of three NMEs targeted orphan indications each year (Fig. 3). In the current decade, on average 12 NMEs targeting orphan indications have been introduced each year. This represented an absolute as well as a proportional increase in NME approvals for orphan indications. For example, the number of NMEs targeting orphan indications has risen threefold from the 1980s to the current decade. Biotechnology companies appear to place particular emphasis on orphan indications. Orphan indications represented 45% of NMEs developed by biotechnology companies as compared with 14% of indications for NMEs approved for pharmaceutical companies.
Concluding remarks and implications A major finding of our present study is that biotechnology companies have placed greater emphasis on certain indications (e.g. oncology) and approval strategies (e.g. orphan diseases) than conventional pharmaceutical companies. Current morbidity and mortality numbers largely reflect the successes of past drug development activities. According to records kept by the www.drugdiscoverytoday.com
3
Features PERSPECTIVE
FIGURE 3
Increasing emphasis on orphan drug approvals. (a) The average annual rate of new molecular entities (NMEs) initially approved for targeting of orphan disease indications is shown. Note the data for the 1980s represent the annual average after 1983 [following passage of the Orphan Drug Act (ODA)]. (b) The relative proportion of orphan indications (compared with all approvals) demonstrates a steady increase in targeting of orphan indications. (c) The proportion of drugs initially approved for orphan indications was compared between pharmaceutical and biotechnology industries. Whereas pharmaceutical companies were granted a higher number of orphan approvals, these indications represented a smaller proportion of total approvals.
DRUDIS-1424; No of Pages 4 PERSPECTIVE
Features PERSPECTIVE
Centers for Disease Control and Prevention (CDC), pneumonia, tuberculosis and influenza infection were leading causes of death from 1900 through to 1940 [4]. Combined age-adjusted rates of death routinely exceeded 400 per 100 000 [5]. However, the introduction of sulfa drugs, later antibiotics and vaccines, reduced influenza- or pneumoniarelated deaths to an age-adjusted rate of 15.1 fatalities per year by 2013 [4]. Heart disease, cancer, stroke and chronic lower respiratory diseases are now the current leading causes of death in the USA [4]. Major causes of morbidity include high prevalence of heart disease, smoking, diabetes and obesity. Heart disease has remained a steady target of new drug approval but underperforms in terms of NMEs targeted against cardiovascular diseases. This might reflect the fact that nonpharmacologic means of intervention (e.g. surgery, changes in lifestyle) can also combat the disease. Likewise, the work herein does not address the complexity of decision-making that guides drug development decisions, including increased understanding of pathophysiology, the roles of payers (e.g. government and insurance companies), as well as general changes in the political and economic climates (e.g. the ongoing debate about healthcare), to name but a few. Two NMEs have been approved targeting cessation of cigarette smoking despite the general understanding that high rates of smoking critically contribute to morbidity and mortality. The rates of NMEs targeting metabolic diseases and obesity likewise have been underrepresented but recent trends suggest these indications are beginning to gain greater attention from the drug development community. The biopharmaceutical industry has been responsive to incentives, such as the ODA of 1983. In the current decade, more than one-third of all NMEs have been approved to target orphan indications. Historically, pharmaceutical
4
www.drugdiscoverytoday.com
Drug Discovery Today Volume 00, Number 00 June 2014
companies sought to develop large, sustainable markets, ideally by coupling high-incidence indications with the need for chronic intervention. Prominent examples include the emphasis on hypertension, ulcers or hypercholesteremia [6]. Treatments for orphan indications are often incentivized by tax advantages and other financial incentives. Drugs targeting orphan indications increasingly have prices that approach or even exceed the costs for new cancer medications (which historically have been among the most lucrative drugs). Although this is a strong current trend, such approaches could be at risk if ceilings in reimbursement were to be imposed by major payers (e.g. insurance companies or Medicaid or Medicare). Although orphan indications are, by definition, limited to a small population, some drugs targeting orphan indications can be more broadly utilized in subsequent applications or approvals. This approach has been widely used for oncology drugs, where an initial approval for an unmet need is followed by a compendium expansion to a broader range of patient populations. Such a strategy can increase sales and mitigate the risks associated with the aforementioned price ceilings. Although not the focus of our present report, future analyses could determine the fate of drugs originally approved for orphan indications to determine whether these were subsequently broadened to nonorphan indications. A recent study demonstrated an increase in the proportion of priority applications [7]. Under the Prescription Drug User Act (PDUFA), priority review is directed to drugs that represent ‘significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications’. According to this study, priority applications currently stand at a 30-year high. Our findings are consistent with this and we find, in particular, that biotechnology
companies have been particularly eager to embrace this approach (data not shown). Altogether, the dynamics reported herein reflect considerable success in terms of the ability of the industry to pivot in response to changing market and public health demands. Yet, the same drivers that increase commercial attraction must be balanced against overall impact on public health. Given the finite resources available to biopharmaceutical companies, future decisions regarding the application of R&D resources (and incentives by regulators guiding these decisions) might need to reflect upon such comments to balance the relative importance of need, severity and incidence. References 1 Kinch, M.S. et al. (2014) An overview of FDA-approved new molecular entities: 1827–2013. Drug Discov. Today http://dx.doi.org/10.1016/j.drudis.2014.03.018 2 Kinch, M.S. (2014) The rise (and decline?) of biotechnology. Drug Discov. Today http://dx.doi.org/ 10.1016/j.drudis.2014.04.006 3 Wellman-Labadie, O. and Zhou, Y. (2010) The US Orphan Drug Act: rare disease research stimulator or commercial opportunity? Health Policy 95, 216–228 4 National Center for Health Statistics. (2013) Health, United States, 2012: With Special Feature on Emergency Care. In: United States Department of Health & Human Services CfDCaP (National Center for Health Statistics, ed), Centers for Disease Control 5 CDC. (2014) Vital Statistics of the United States. Atlanta, GA 6 Hunt, V. et al. (2011) A wake-up call for Big Pharma. McKinsey Quarterly December 7 Kaitin, K.I. and DiMasi, J.A. (2011) Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000–2009. Clin. Pharmacol. Ther. 89, 183–188
Michael S. Kinch, Janie Merkel, Sheila Umlauf Yale Center for Molecular Discovery, Yale University, 600 West Campus Drive, West Haven, CT 06516, USA
PERSPECTIVE
feature Trends in pharmaceutical targeting of clinical indications: 1930–2013 Michael S. Kinch, [email protected], [email protected], Janie Merkel and Sheila Umlauf
Introduction Change in the pharmaceutical industry has been constant and dynamic since its inception in the 1930s. Nowhere is this more apparent than in the therapeutic applications of new medicines. As part of a review of new molecular entities (NMEs), we seek to identify the therapeutic indications targeted by newly approved drugs.
Targeting major indications As part of our overall analysis of NMEs approved by the FDA, the details of which can be found in the first article of this series [1], the indications for each of the 1453 NMEs approved from 1930 through to the end of 2013 were assigned to major categories (e.g. oncology, cardiovascular diseases, etc.). Using this approach, 20 groups of indications captured the majority of NME approvals, with at least ten different NMEs in each category. A minority of NMEs were counted in two categories (e.g. an antibiotic for ocular use
would be found in infectious diseases and ophthalmology) (Fig. 1a). Infectious diseases represented the most common set of indications, with 299 NMEs (or more than one in five NMEs approved) targeting microorganisms. Other leading indications include cardiovascular diseases (211 NMEs; 14.5% of all NMEs), oncology (193; 13.3%) and autoimmunity/inflammation (180; 12.4%). These four indications capture 60.8% of all NMEs approved by the FDA. Beyond these four, the number of NMEs drops precipitously, with the next largest five indications (metabolic, neurological, psychiatric diseases, as well as pain/itch and ophthalmology) ranging from 50 to 80 NMEs each. Having established the major indications targeted by NMEs, we asked if and how the types of indications changed from 1930 to the present day (Fig. 1b and c). In the period spanning 1961 through to 1985 more than one-quarter of NMEs was devoted to infectious diseases. Since that
1359-6446/06/$ - see front matter ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.drudis.2014.05.021
Features PERSPECTIVE
An analysis of FDA-approved new molecular entities (NMEs) reveals trends in therapeutic applications. Four groupings (infectious diseases, cardiovascular diseases, autoimmune/inflammatory diseases and cancer) capture more than 60% of NMEs. Infectious diseases are the most targeted indications. Near the turn of the new millennium, the rate of new approvals for infectious diseases decreased. The absolute and relative number of NMEs targeting psychiatric, neurological and pain/itch indications also declined. By contrast, NMEs targeting cancer have risen in the past two decades as have NMEs targeting orphan indications. These results suggest the drug development community has largely been responsive to public health and market needs. However, finite resources might indicate emphasis on some unmet needs could come at the cost of others.
time, the relative proportion has shrunk to a current level of 15%. This represents a proportional and absolute decrease. At its peak, more than six new drugs targeting infectious diseases were approved annually. As of the first decade in the new century, this decreased to an average of 4.4 NMEs per year. The causes of the decline in emphasis on infectious disease were not assessed in the present study. These could include the rise of vaccines, increased understanding of pathogens and the disease process as well as business trends such as the relative return on investment as perceived by key decision-makers within the biopharmaceutical industry. NMEs devoted to oncology have gained more prominence. Whereas fewer than 5% of new drugs introduced in the 1930s targeted cancer, the fraction today exceeds one-third. In absolute terms, the number of new oncology drugs has increased from less than one approval every five www.drugdiscoverytoday.com
1
DRUDIS-1424; No of Pages 4 PERSPECTIVE
(b)
Nutrition
40%
Urinary
35%
Bleeding
30% NMEs targeting therapeutic class
(a)
Drug Discovery Today Volume 00, Number 00 June 2014
Bone Ulcer Digestive Reproductive Hormonal
Infection Oncology Metabolic
Cardiovascular Immunology
25% 20% 15% 10%
Sleep disorder
5%
Respiratory 0% 1940
Anaesthesia
1960
1980
2000
Opthamology Pain/itch
(c)
15%
Psychiatric NMEs targeting therapeutic class
Neurological Metabolic Autoimune/inflammation Oncology Cardiovascular Infectious diseases 0
50
Neurological Psychiatry Pain/Itch Opthamology Anaesthesia
12% 9% 6% 3% 0% 1940
100 150 200 250 300 Total NMEs
1960
1980
2000 Drug Discovery Today
Features PERSPECTIVE
FIGURE 1
New molecular entity (NME) targeting of indications. (a) The leading 20 therapeutic applications for NMEs are indicated. Note that the leading four indications encompass more than 60% of all NMEs. (b,c) The top ten indications were assessed over time on a decade-by-decade basis.
Indications targeted (1981–2013)
Pharmaceutical Rank (share of portfolio)
Biotechnology Rank (share of portfolio)
Infectious diseases
1 (21%)
2 (18%)
Cardiovascular
2 (16%)
4 (11%)
Oncology
3 (14%)
1 (29%)
Autoimmune/inflammation
3 (14%)
3 (12%)
Metabolic
5
(6%)
5 (9%)
Neurological
6
(6%)
7 (4%)
Psychiatric
7 (5%)
8 (2%)
Pain/itch
9 (3%)
8 (2%)
Ophthalmology
8 (4%)
6 (6%)
Anesthesia
10 (3%)
None Drug Discovery Today
FIGURE 2
Similarities and differences between pharmaceutical and biotechnology companies. Shown are the relative contributions of pharmaceutical and biotechnology industries to the components of the collective leading ten indications (left column). 2
www.drugdiscoverytoday.com
DRUDIS-1424; No of Pages 4 Drug Discovery Today Volume 00, Number 00 June 2014
(b)
12
40% 35%
10
Fraction of orphan NMEs
Average annual orphan NMEs
(a)
PERSPECTIVE
8 6 4 2
30% 25% 20% 15% 10% 5%
0
0% 1980s
1990s
2000s
2010s
(c)
1980s
Orphan NMEs
Orphan fraction
Biotechnology
88
45%
Pharmaceutical
97
14%
1990s
2000s
2010s
Drug Discovery Today
years (in the 1930s and 1940s) to a current annual rate of 11 NMEs. Perhaps the most dramatic changes are seen with NMEs targeting pain/itch and anesthesia. One in ten drugs targeted these indications in the early years of the pharmaceutical industry. By contrast, the current decade has not yet witnessed a new approval in either indication. NMEs targeting psychiatric indications also peaked in the 1960s but new entries have decreased by 75%. With the exception of psychiatric drugs, many shifts began in the 1980s. This timeframe is coincident with the rise of biotechnology. Thus, we compared indications targeted by conventional pharmaceutical and biotechnology companies (Fig. 2). For the purpose of this analysis, we broadly designate organizations founded before 1971 as pharmaceutical and those after 1971 as biotechnology companies, please see an earlier paper in the series for a discussion of the imperfect definition of biotechnology [2]. We then analyzed all drugs approved during or after 1981 (the first year that a biotechnology company had actively contributed to an NME).
Whereas four indications (infectious, cardiovascular, immunological diseases and cancer) capture two-thirds of all NME approvals for pharmaceutical and biotechnology companies, the portfolios of biotechnology companies placed twice as much emphasis on oncology products as their pharmaceutical peers (29% vs 14%, respectively). Thus, the rise of biotechnology coincides with the increase in oncology approvals over the past three decades. By contrast, biotechnology companies were underrepresented for drugs targeting cardiovascular, psychiatric and/or anesthesia applications.
Rise of orphan indications The Orphan Drug Act (ODA), passed in January 1983 [3], provided marketing and tax incentives for companies that develop drugs targeting disorders that affect fewer than 200 000 people in the USA. Thus, we asked if the ODA impacted drug development and how the two industries responded to these changes. These analyses focused on NMEs where the initial approval qualified as an orphan indication (excluding approved drugs that were subsequently approved for use in orphan diseases).
In the time period immediately following approval of the ODA in 1983, an average of three NMEs targeted orphan indications each year (Fig. 3). In the current decade, on average 12 NMEs targeting orphan indications have been introduced each year. This represented an absolute as well as a proportional increase in NME approvals for orphan indications. For example, the number of NMEs targeting orphan indications has risen threefold from the 1980s to the current decade. Biotechnology companies appear to place particular emphasis on orphan indications. Orphan indications represented 45% of NMEs developed by biotechnology companies as compared with 14% of indications for NMEs approved for pharmaceutical companies.
Concluding remarks and implications A major finding of our present study is that biotechnology companies have placed greater emphasis on certain indications (e.g. oncology) and approval strategies (e.g. orphan diseases) than conventional pharmaceutical companies. Current morbidity and mortality numbers largely reflect the successes of past drug development activities. According to records kept by the www.drugdiscoverytoday.com
3
Features PERSPECTIVE
FIGURE 3
Increasing emphasis on orphan drug approvals. (a) The average annual rate of new molecular entities (NMEs) initially approved for targeting of orphan disease indications is shown. Note the data for the 1980s represent the annual average after 1983 [following passage of the Orphan Drug Act (ODA)]. (b) The relative proportion of orphan indications (compared with all approvals) demonstrates a steady increase in targeting of orphan indications. (c) The proportion of drugs initially approved for orphan indications was compared between pharmaceutical and biotechnology industries. Whereas pharmaceutical companies were granted a higher number of orphan approvals, these indications represented a smaller proportion of total approvals.
DRUDIS-1424; No of Pages 4 PERSPECTIVE
Features PERSPECTIVE
Centers for Disease Control and Prevention (CDC), pneumonia, tuberculosis and influenza infection were leading causes of death from 1900 through to 1940 [4]. Combined age-adjusted rates of death routinely exceeded 400 per 100 000 [5]. However, the introduction of sulfa drugs, later antibiotics and vaccines, reduced influenza- or pneumoniarelated deaths to an age-adjusted rate of 15.1 fatalities per year by 2013 [4]. Heart disease, cancer, stroke and chronic lower respiratory diseases are now the current leading causes of death in the USA [4]. Major causes of morbidity include high prevalence of heart disease, smoking, diabetes and obesity. Heart disease has remained a steady target of new drug approval but underperforms in terms of NMEs targeted against cardiovascular diseases. This might reflect the fact that nonpharmacologic means of intervention (e.g. surgery, changes in lifestyle) can also combat the disease. Likewise, the work herein does not address the complexity of decision-making that guides drug development decisions, including increased understanding of pathophysiology, the roles of payers (e.g. government and insurance companies), as well as general changes in the political and economic climates (e.g. the ongoing debate about healthcare), to name but a few. Two NMEs have been approved targeting cessation of cigarette smoking despite the general understanding that high rates of smoking critically contribute to morbidity and mortality. The rates of NMEs targeting metabolic diseases and obesity likewise have been underrepresented but recent trends suggest these indications are beginning to gain greater attention from the drug development community. The biopharmaceutical industry has been responsive to incentives, such as the ODA of 1983. In the current decade, more than one-third of all NMEs have been approved to target orphan indications. Historically, pharmaceutical
4
www.drugdiscoverytoday.com
Drug Discovery Today Volume 00, Number 00 June 2014
companies sought to develop large, sustainable markets, ideally by coupling high-incidence indications with the need for chronic intervention. Prominent examples include the emphasis on hypertension, ulcers or hypercholesteremia [6]. Treatments for orphan indications are often incentivized by tax advantages and other financial incentives. Drugs targeting orphan indications increasingly have prices that approach or even exceed the costs for new cancer medications (which historically have been among the most lucrative drugs). Although this is a strong current trend, such approaches could be at risk if ceilings in reimbursement were to be imposed by major payers (e.g. insurance companies or Medicaid or Medicare). Although orphan indications are, by definition, limited to a small population, some drugs targeting orphan indications can be more broadly utilized in subsequent applications or approvals. This approach has been widely used for oncology drugs, where an initial approval for an unmet need is followed by a compendium expansion to a broader range of patient populations. Such a strategy can increase sales and mitigate the risks associated with the aforementioned price ceilings. Although not the focus of our present report, future analyses could determine the fate of drugs originally approved for orphan indications to determine whether these were subsequently broadened to nonorphan indications. A recent study demonstrated an increase in the proportion of priority applications [7]. Under the Prescription Drug User Act (PDUFA), priority review is directed to drugs that represent ‘significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications’. According to this study, priority applications currently stand at a 30-year high. Our findings are consistent with this and we find, in particular, that biotechnology
companies have been particularly eager to embrace this approach (data not shown). Altogether, the dynamics reported herein reflect considerable success in terms of the ability of the industry to pivot in response to changing market and public health demands. Yet, the same drivers that increase commercial attraction must be balanced against overall impact on public health. Given the finite resources available to biopharmaceutical companies, future decisions regarding the application of R&D resources (and incentives by regulators guiding these decisions) might need to reflect upon such comments to balance the relative importance of need, severity and incidence. References 1 Kinch, M.S. et al. (2014) An overview of FDA-approved new molecular entities: 1827–2013. Drug Discov. Today http://dx.doi.org/10.1016/j.drudis.2014.03.018 2 Kinch, M.S. (2014) The rise (and decline?) of biotechnology. Drug Discov. Today http://dx.doi.org/ 10.1016/j.drudis.2014.04.006 3 Wellman-Labadie, O. and Zhou, Y. (2010) The US Orphan Drug Act: rare disease research stimulator or commercial opportunity? Health Policy 95, 216–228 4 National Center for Health Statistics. (2013) Health, United States, 2012: With Special Feature on Emergency Care. In: United States Department of Health & Human Services CfDCaP (National Center for Health Statistics, ed), Centers for Disease Control 5 CDC. (2014) Vital Statistics of the United States. Atlanta, GA 6 Hunt, V. et al. (2011) A wake-up call for Big Pharma. McKinsey Quarterly December 7 Kaitin, K.I. and DiMasi, J.A. (2011) Pharmaceutical innovation in the 21st century: new drug approvals in the first decade, 2000–2009. Clin. Pharmacol. Ther. 89, 183–188
Michael S. Kinch, Janie Merkel, Sheila Umlauf Yale Center for Molecular Discovery, Yale University, 600 West Campus Drive, West Haven, CT 06516, USA
