scholarly journals The Potential Benefit of Expedited Development and Approval Programs in Precision Medicine

2021 ◽  
Vol 11 (1) ◽  
pp. 45
Author(s):  
Ariel Kantor ◽  
Susanne B. Haga
Keyword(s):  
Precision Medicine ◽  
Fast Track ◽  
Unmet Needs ◽  
Drug Approval ◽  
Priority Review ◽  
The Us ◽  
Causes Of Disease ◽  
Accelerated Approval ◽  
Legislative Changes ◽  
Innovative Drugs

Background: Increased understanding of the molecular causes of disease has begun to fulfill the promise of precision medicine with the development of targeted drugs, particularly for serious diseases with unmet needs. The drug approval regulatory process is a critical component to the continued growth of precision medicine drugs and devices. To facilitate the development and approval process of drugs for serious unmet needs, four expedited approval programs have been developed in the US: priority review, accelerated approval, fast track, and breakthrough therapy programs. Methods: To determine if expedited approval programs are fulfilling the intended goals, we reviewed drug approvals by the US Food and Drug Administration (FDA) between 2011 and 2017 for new molecular entities (NMEs). Results: From 2011 through 2017, the FDA approved 250 NMEs, ranging from 27 approvals in 2013 to 46 in 2017. The NME approvals spanned 22 different disease classes; almost one-third of all NMEs were for oncology treatments. Conclusions: As these pathways are utilized more, additional legislative changes may be needed to re-align incentives to promote continued development of innovative drugs for serious unmet needs in a safe, efficacious, and affordable manner.

Safety-Related Postmarketing Modifications of Drugs for Hematological Malignancies

2019 ◽  
Vol 143 (1) ◽  
pp. 73-77
Author(s):  
Anat Gafter-Gvili ◽  
Ariadna Tibau ◽  
Pia Raanani ◽  
Daniel Shepshelovich
Keyword(s):  
Hematological Malignancies ◽  
New Drugs ◽  
Priority Review ◽  
Regulatory Review ◽  
Regulatory Pathways ◽  
The Us ◽  
Black Box Warnings ◽  
Accelerated Approval ◽  
Drug Approvals ◽  
Approved Drugs

The prevalence of safety-related postmarketing label modifications of medications for hematological malignancies is unknown. We identified 35 new drugs indicated for hematological malignancies approved by the US Food and Drug Administration between January 1999 and December 2014. Characteristics of supporting trials and safety-related label modifications from approval to December 2017 were collected from drug labels. Regulatory review and approval pathways were also collected. New drug approvals were supported by trials with a median of 167 patients (interquartile range 115–316). All drugs were approved based on surrogate endpoints. Twenty-seven drug approvals (77%) were not supported by randomized controlled trials. All drugs received orphan drug designation, and most were granted fast track designation, priority review, and accelerated approval (83, 74, and 60%, respectively). A total of 28 drugs (80%) had postmarketing safety-related label modifications. Additions to black box warnings, contraindications, warnings and precautions, and common adverse reactions were identified in 31, 11, 77, and 46% of drugs, respectively. Five drugs (14%) were permanently or temporarily withdrawn from the US market. Drugs for hematological malignancies are often approved based on limited evidence through expedited regulatory pathways with incomplete safety profiles. Hematologists should be vigilant for unrecognized side effects when prescribing newly approved drugs.

Trend of Drug Approval on Hematological Malignancies in the U.S. and Japan.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3120-3120
Author(s):  
Fumitaka Nagamura ◽  
Arinobu Tojo ◽  
Tokiko Nagamura-Inoue ◽  
Aikichi Iwamoto
Keyword(s):  
Clinical Trials ◽  
Hematological Malignancies ◽  
Drug Evaluation ◽  
Geographical Location ◽  
Drug Approval ◽  
New Concepts ◽  
The Us ◽  
Accelerated Approval ◽  
Outstanding Result ◽  
The U.S

Abstract Introduction: Characteristics on hematological malignancies, e.g., many of them arise from one chromosomal abnormality and there are many molecules discriminating malignancies from normal cells, have recently played very important role on the development of novel therapeutic options. Molecular-targeted therapies, such as antibodies and signal inhibitors, are good examples. On the other hand, drug evaluation and approval methods have been suffered from the difficulties in fastening approval periods and evaluating efficacies and safeties more precisely, especially in the case of these entirely new concepts of drugs. In this study, we clarified the trends of drug approval on hematological malignancies in the U.S. and Japan. By the comparison, the trends were made more clearly. Methods: Drugs for hematological malignancies, including CMPDs, which approved by December 2004 in the US or Japan were eligible. Supportive drugs, immunomodulators, biochemical modulators, and “off-label use” were excluded. Package inserts, reviews by agencies, publications on clinical trials were examined. The geographical analysis on clinical trials of oncologic drugs was based on the previous report (Proc ASCO2003; 22:534a). Results: Forty-six drugs were approved in the U.S., and 43 were in Japan. Twenty-seven drugs were approved in both countries. Twenty-two of 27 drugs were approved earlier in the U.S., and the dates of approval were considerably earlier in the U.S. (median: 46.0 Mo, mean: 54.7 Mo). These differences have not been shorten when compared in every 10-year period. Eight drugs were approved as “Accelerated Approval”, which stated in CFRs as “Subpart H”. Seven of eight “accelerated approval” drugs were approved only in the U.S. Furthermore, around one-thirds of drugs (7/19: 36.8%) approved only in the U.S. were based on “accelerated approval”. However, one drug approved as “accelerated approval” could have shown its clinical benefit in the designated clinical trial. Among the drugs approve only in the U.S., the number of drugs for “first line”, “second line or thereafter”, and “not specified” were 2, 13, 4, respectively. The geographical comparison of clinical trials was summarized in the Table below. The ratio of non-U.S. studies was considerably low in hematological malignancies. In Japan, the data on clinical trials exclusively performed in Japan was generally stated. Five drugs approved only in Japan were approved in the US for diseases other than hematological malignancies, while no drug was approved in the reverse case. Conclusion: “Accelerated approval” is useful for fastening the period until the approval, although the problem whether “surrogate markers” leads to “survival and/or QOL benefit” has not been clarified, yet. The outstanding result that most of pivotal/supportive studies were not “non-U.S.” studies may be caused by the superiority of drug development, especially in new concepts of drugs for hematological malignancies and the ability to conduct appropriate clinical trials in the U.S. On the contrary, the expansion of the indication would be the problem in the U.S. to be considered. Geographical Location of Studies U.S. only U.S. & Canada U.S. & Europe Non-U.S. Total All oncology drugs (1986.1–2002.9) 77 (43.5%) 23 (13.0%) 35 (19.8%) 42 (23.7%) 177 studies Hematological malignancies (1986.1–2004.12) 27 (62.8%) 4 (9.3%) 9 (20.9%) 3 (7.0%) 42 studies

Faster approvals?: Trends in the use of FDA’s expedited approval programs for oncology medications.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18270-e18270
Author(s):  
Lisa Ambrosini Vadola ◽  
Monique A Pond ◽  
Ann Winter-Vann ◽  
Robin Whitsell
Keyword(s):  
Health Care Providers ◽  
Fast Track ◽  
Priority Review ◽  
Pharmaceutical Companies ◽  
Care Providers ◽  
Regulatory Pathways ◽  
Oncology Drug ◽  
Accelerated Approval ◽  
Fast Track Designation ◽  
Speed To Market

e18270 Background: With the importance of speed-to-market and addressing unmet needs, pharmaceutical companies have sought accelerated approvals through the Food and Drug Administration (FDA). Introduced with the FDA Safety and Innovation Act (FDASIA) of 2012, Breakthrough Therapy Designation (BTD) has become an important mechanism for approval of serious and life-threatening conditions that do not have adequate therapies. Notably, these pathways have been ill-understood by both pharmaceutical companies and health care providers. This study assessed how BTD and other FDA designations have played a role in the approval of oncology drug marketing applications and evaluated trends in the use of these regulatory pathways. Methods: We analyzed publicly available data on novel oncology drug approvals by the FDA from 2012-2016, including the 4 expedited programs for serious conditions (BTD, Accelerated Approval, Fast Track, and Priority Review). Results: Of the 43 novel oncology drugs approved by the FDA between 2012-2016, 42 used at least 1 of the expedited approval programs, including 65% that used ≥2 programs and 35% that used ≥3 programs. The BTD has been used by 15 of the 43 (35%) approved novel oncology drugs since 2012. The use of the BTD, Accelerated Approval pathway, and Priority Review designation among approved oncology drugs has generally increased each year from 2012-2016, while the use of the Fast Track designation has decreased over the same time period. Conclusions: Companies seeking oncology approvals often use more than one expediting strategy. Alone or in combinations, the BTD, Accelerated Approval, and Priority Review have been shown to play an increasingly important role in oncology drug development. Data collected between 2012-2016 suggest that use of BTD is growing more common, while use of the Fast Track designation has decreased among approved oncology drugs. Additional expedited approval programs have remained steady or increased since the FDA introduced BTD. Based on these observations, we anticipate use of the BTD, Accelerated Approval, and Priority Review designation will grow in future oncology drug applications.

Patient-Reported Outcomes Labeling for Products Approved by the Office of Hematology and Oncology Products of the US Food and Drug Administration (2010-2014)

2016 ◽  
Vol 34 (16) ◽  
pp. 1928-1934 ◽  
Author(s):  
Ari Gnanasakthy ◽  
Carla DeMuro ◽  
Marci Clark ◽  
Emily Haydysch ◽  
Esprit Ma ◽  
...  
Keyword(s):  
Drug Administration ◽  
Study Design ◽  
Fast Track ◽  
Food And Drug Administration ◽  
The United States ◽  
Priority Review ◽  
Product Labeling ◽  
End Points ◽  
Patient Reported ◽  
The Us

Purpose To review the use of patient-reported outcome (PRO) data in medical product labeling granted by the US Food and Drug Administration (FDA) for new molecular entities and biologic license applications by the FDA Office of Hematology and Oncology Products (OHOP) between January 2010 and December 2014, to elucidate challenges faced by OHOP for approving PRO labeling, and to understand challenges faced by drug manufacturers to include PRO end points in oncology clinical trials. Methods FDA Drug Approval Reports by Month were reviewed to obtain the number of new molecular entities and biologic license applications approved from 2010 to 2014. Drugs approved by the FDA OHOP during this period were selected for further review, focusing on brand and generic name; approval date; applicant; indication; PRO labeling describing treatment benefit, measures, end point status, and significant results; FDA reviewer feedback on PRO end points; and study design of registration trials. First in class, priority review, fast track, orphan drug, or accelerated approval status was retrieved for selected oncology drugs from 2011 to 2014. Descriptive analyses were performed by using Microsoft Excel 2010. Results Of 160 drugs approved by the FDA (2010-2014), 40 were approved by OHOP. Three (7.5%) of the 40 received PRO-related labeling (abiraterone acetate, ruxolitinib phosphate, and crizotinib). Compared with nononcology drugs (2011-2014), oncology drugs were more likely to be orphan and first in class. The majority of oncology drug reviews by FDA were fast track, priority, or accelerated. Conclusion Although symptoms and functional decrements are common among patients with cancer, PRO labeling is rare in the United States, likely because of logistical hurdles and oncology study design. Recent developments within the FDA OHOP to capture PROs in oncology studies for the purpose of product labeling are encouraging.

scholarly journals 1235. On the Edge of Tomorrow: Expedited Regulatory Pathways for Anti-Infective Therapies

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S637-S637
Author(s):  
Cem Atillasoy ◽  
Panagiotis Gourlias
Keyword(s):  
Infectious Disease ◽  
Infectious Diseases ◽  
Drug Development ◽  
Orphan Drug ◽  
Fast Track ◽  
Orphan Drug Status ◽  
Priority Review ◽  
Drug Status ◽  
Development Programs ◽  
Accelerated Approval

Abstract Background The FDA has developed expedited review programs and pathways to increase drug development for products that have a major clinical benefit. These programs include: Fast Track, Orphan Drug Status, Accelerated Approval, Priority Review, Breakthrough Therapy (BTD) and Qualified Infectious Disease Products (QIPD). Given the heightened awareness of infectious diseases--and emerging global threats, such as resistant bacteria and Ebola—academia and industry have developed and received approval for 88 new infectious disease agents. The objective of this study was to assess the use of expedited review pathways for the 88 anti-infective agents that were approved between 2001-2020. FDA Expedited Drug Development Programs Methods We analyzed the FDA Drug Approval Database entitled, “Compilation of CDER New Molecular Entity (NME) Drug and New Biologic Approvals” for anti-infective therapies that were approved after 2000. Anti-infective therapies were defined as agents that were used to treat or prevent infectious diseases and include antibiotics, antivirals and antifungals. Our analysis focused on a comparison of the percentage of approved anti-infective agents that used each of the aforementioned designations across 2 decades (2001-2010 & 2011-2020). A drug may have one, none, or multiple of these designations. Results There were significant differences in the percentage of anti-infective agents approved with priority review, fast track and accelerated approval in 2001-2010 compared to 2011-2020 (See Results Figure 1) BTD and QIDP did not exist until 2012, thus preventing comparisons between decades. QIDP • Between 2012-2020, 16 anti-infectives have been approved with QIDP. From 2017-2020, 40% (n=10) of approved anti-infectives had QIDP. Orphan Drug Status: • Between 2017-2020, 32% of anti-infectives approved have the orphan drug designation. Comparison of FDA Expedited Drug Development Programs use between 2001-2010 and 2011-2020 Conclusion Our findings indicate Priority Review and Fast Track use has increased since 2010 among anti-infective products. Additionally, our analyses indicate that since 2017 there has been increased use of Orphan Drug Status and QIDP. However, there has been limited use of Breakthrough Therapy and Accelerated Approvals. These two pathways should be increasingly considered by academia, industry and the FDA to further expedite innovative anti-infective development. Disclosures All Authors: No reported disclosures

scholarly journals Time to inclusion in clinical guidance documents for non-oncological orphan drugs and biologics with expedited FDA designations: a retrospective survival analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e057744
Author(s):  
Ryan Rodriguez ◽  
Rachel Brunner ◽  
Samantha Spencer ◽  
Dima M Qato
Keyword(s):  
Survival Analysis ◽  
Fast Track ◽  
Orphan Drugs ◽  
Priority Review ◽  
Guidance Document ◽  
Entire Cohort ◽  
Fda Approval ◽  
Life Threatening ◽  
Guidance Documents ◽  
Accelerated Approval

ObjectivesDrug and biological products that treat rare, serious or life-threatening conditions can receive US Food and Drug Administration (FDA) orphan designation and expedited programme designations (accelerated approval, breakthrough therapy, fast track or priority review) meant to incentivise development. Timely recommendations from guidance documents may encourage more rapid and appropriate use and access to these medicines for serious conditions. We sought to determine time between FDA approval and inclusion in guidance documents for non-oncological orphan products overall and by number and type of expedited programme designations.Design and settingRetrospective survival analysis of non-oncological orphan products with ≥1 expedited designation approved since 1992. In June 2020, PubMed, Turning Research into Practice and Guideline Central databases were searched to identify guidance documents influencing US practice that included each product.Main outcomes and measuresThe primary outcome was time to guidance inclusion, defined as any recommendation on use provided within the recommendation framework used by the guidance document.ResultsAmong 135 included non-oncological orphan products, 97.0% (n=131) were designated with priority review, 49.6% (n=67) fast track, 16.3% (n=22) breakthrough therapy and 14.1% (n=19) accelerated approval. Sixty per cent of products (n=81) received ≥2 designations. Overall, 74.1% (n=100) were included in a guidance document. The median time to inclusion was 2.87 years (IQR 2.21–4.18) for the entire cohort. In survival analyses, guidance inclusion was more likely to occur earlier for products with ≥2 designations (HR, 1.84; 95% CI 1.21 to 2.79) and for those with fast-track designation compared with priority review (HR 1.40; 95% CI 1.02 to 2.0). Of 35 products not included in a guidance document, 54.3% (n=19) were approved in 2018 or later.ConclusionsAmong non-oncological orphan products with priority designations, nearly 3 years had passed between FDA approval and inclusion in any guidance document. These findings suggest that despite efforts to expedite availability, appropriate access to these treatments may be delayed because of the lack of timely guidance on their use in clinical practice.

scholarly journals Caring for Older Patients With Cancer: Estimates of the Prevalence, Burden, and Unmet Needs of Caregivers in the United States

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 690-690
Author(s):  
Erin Kent
Keyword(s):  
Family Caregivers ◽  
Older Patients ◽  
Unmet Needs ◽  
The United States ◽  
Population Based ◽  
Data Sources ◽  
Behavioral Risk ◽  
Ripple Effect ◽  
The Us ◽  
National Trends

Abstract In 2020, ~1.8 million Americans are expected to be newly diagnosed with cancer, with approximately 70% of cases diagnosed over the age of 65. Cancer can have a ripple effect, impacting not just patients themselves, but their family caregivers. This presentation will provide an overview of the estimates of the number of family caregivers caring for individuals with cancer in the US, focusing on older patients, from several population-based data sources: Caregiving in the US 2020, the Health Information National Trends Survey (HINTS, 2017-2019), the Behavioral Risk Factors Surveillance System (BRFSS, 2015-2019), and the National Health and Aging Trends (NHATS) Survey. The presentation will compare features of the data sources to give a comprehensive picture of the state of cancer caregiving. In addition, the presentation will highlight what is known about the experiences of cancer caregivers, including caregiving characteristics, burden, unmet needs, and ideas for improving support for family caregivers.

Enrollment disparities in cancer clinical trials leading to FDA approvals between 2008 and 2020.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18501-e18501
Author(s):  
Ryan Huu-Tuan Nguyen ◽  
Yomaira Silva ◽  
Vijayakrishna K. Gadi
Keyword(s):  
Prostate Cancer ◽  
United States ◽  
Clinical Trials ◽  
Drug Approval ◽  
The United States ◽  
Cancer Clinical Trials ◽  
Cancer Prevalence ◽  
Fda Approval ◽  
The Us ◽  
Enrollment Data

e18501 Background: Cancer clinical trials based in the United States (US) have lacked adequate representation of racial and ethnic minorities, the elderly, and women. Pivotal clinical trials leading to United States Food and Drug Administration (FDA) approval are often multi-national trials and may also lack generalizability to underrepresented populations in the United States. We determined the racial, ethnic, age, and sex enrollment in pivotal trials relative to the US cancer population. Methods: We reviewed the FDA’s Drug Approvals and Databases for novel and new use drug approvals for breast, colorectal, lung, and prostate cancer indications from 2008 through 2020. Drugs@FDA was searched for drug approval summaries and FDA labels to identify clinical trials used to justify clinical efficacy that led to FDA approval. For eligible trials, enrollment data were obtained from FDA approval summaries, FDA labels, ClinicalTrials.gov, and corresponding journal manuscripts. Enrollment Fraction (EF) was calculated as enrollment in identified clinical trials divided by 2017 SEER cancer prevalence. All data sources were publicly available. Results: From 2008 through 2020, 60 drugs received novel or new use drug approval for breast, colorectal, lung, or prostate cancer indications based on 66 clinical trials with a total enrollment of 36,830. North America accounted for 9,259 (31%) enrollees of the 73% of trials reporting location of enrollment. Racial demographics were reported in 78% of manuscripts, 66% of ClinicalTrials.gov pages, and 98% of FDA labels or approval summaries. Compared with a 0.4% enrollment fraction among White patients, lower enrollment fractions were noted in Hispanic (0.2%, odds ratio [OR] vs White, 0.46; 95% confidence interval [CI], 0.43 to 0.49, P< 0.001) and Black (0.1%, OR 0.29; 95% CI 0.28 to 0.31, P< 0.001) patients. Elderly patients (age ≥ 65 years) were less likely than younger patients to be enrollees (EF 0.3% vs 0.9%, OR 0.27; 95% CI 0.26 to 0.27, P< 0.001) despite accounting for 61.3% of cancer prevalence. For colorectal and lung cancer trials, females were less likely than males (EF 0.7% vs 1.1%, OR 0.66; 95% CI 0.63 to 0.68, P< 0.001) to be enrolled. Conclusions: Black, Hispanic, elderly, and female patients were less likely to enroll in cancer clinical trials leading to FDA approvals from 2008 to 2020. Race and geographic enrollment data were inconsistently reported in journal manuscripts and ClinicalTrials.gov. The lack of appropriate representation of specific patient populations in these key clinical trials limits their generalizability. Future efforts must be made to ensure equitable access, representation, and reporting of enrollees that adequately represent the US population of patients with cancer.

Care and the caravan: the unmet needs of migrants heading for the US

BMJ ◽  
2018 ◽  
pp. k5315 ◽  
Author(s):  
Angelika Albaladejo
Keyword(s):  
Unmet Needs ◽  
The Us

Venture Funders — Are They the Solution?

1998 ◽  
Vol 12 (2) ◽  
pp. 77-83
Author(s):  
Paul M. Kelley
Keyword(s):  
Small Business ◽  
Birth Rate ◽  
Fast Track ◽  
Government Support ◽  
High Tech ◽  
Investment Company ◽  
Business Investment ◽  
The Us ◽  
Us Government ◽  
Financial Climate

The author briefly describes what venture funders do and how they do it to illuminate the process of high-tech business formation and development. By way of illumination, he gives two short histories of successful university spin-outs that his company, Zero Stage Capital, has helped launch. He then examines how this firm's knowledge and experience may apply in the context of the Scottish university and financial climate, and bearing in mind the goals of Scotland's Technology Ventures strategy. Finally, he discusses the US government support initiatives for small business, the Small Business Investment Company (SBIC) Program. He suggests an approach for its application in increasing the birth-rate of fast-track technology-based ventures in Scotland or in other countries that have the infrastructure to support and enhance the process.

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