Quicker FDA Approval of Cancer Drugs, Courtesy of COVID-19

Purpose The breakthrough therapy program was established in 2012 to expedite the development and review of new medicines. We evaluated the times to approval, efficacy, and safety of breakthrough-designated versus non–breakthrough-designated cancer drugs approved by the US Food and Drug Administration (FDA). Methods We studied all new cancer drugs approved by the FDA between January 2012 and December 2017. Regulatory and therapeutic characteristics (time to FDA approval, pivotal trial efficacy end point, novelty of mechanism of action) were compared between breakthrough-designated and non–breakthrough-designated cancer drugs. Random-effects meta-regression was used to assess the association between breakthrough therapy designation and hazard ratios for progression-free survival (PFS), response rates (RRs) for solid tumors, serious adverse events, and deaths not attributed to disease progression. Results Between 2012 and 2017, the FDA approved 58 new cancer drugs, 25 (43%) of which received breakthrough therapy designation. The median time to first FDA approval was 5.2 years for breakthrough-designated drugs versus 7.1 years for non–breakthrough-designated drugs (difference, 1.9 years; P = .01). There were no statistically significant differences between breakthrough-designated and non–breakthrough-designated drugs in median PFS gains (8.6 v 4.0 months; P = .11), hazard ratios for PFS (0.43 v 0.51; P = .28), or RRs for solid tumors (37% v 39%; P = .74). Breakthrough therapy–designated drugs were not more likely to act via a novel mechanism of action (36% v 39%; P = 1.00). Rates of deaths (6% v 4%; P = .99) and serious adverse events (38% v 36%; P = 0.93) were also similar in breakthrough-designated and non–breakthrough-designated drugs. Conclusion Breakthrough-designated cancer drugs were associated with faster times to approval, but there was no evidence that these drugs provide improvements in safety or novelty; nor was there a statistically significant efficacy advantage when compared with non–breakthrough-designated drugs.

Download Full-text

Monthly and Median Costs of Cancer Drugs at the Time of FDA Approval 1965-2016

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djx173 ◽

2017 ◽

Vol 109 (8) ◽

Cited By ~ 2

Keyword(s):

Cancer Drugs ◽

Fda Approval

Download Full-text

Timing of US Food and Drug Administration (FDA) cancer drug approvals relative to publication of clinical trial results.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.2071 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 2071-2071 ◽

Cited By ~ 1

Author(s):

Ali Raza Khaki ◽

Aakash Desai ◽

Martin W. Schoen ◽

Bishal Gyawali ◽

Eddy J. Chen ◽

...

Keyword(s):

Clinical Trial ◽

Cancer Drug ◽

Cancer Drugs ◽

Cancer Treatments ◽

Fda Approval ◽

Anti Cancer ◽

Accelerated Approval ◽

Drug Approvals ◽

Clinical Trial Results ◽

Careful Assessment

2071 Background: Publication of clinical trial results in peer reviewed literature is essential to inform clinicians regarding the use of new anti-cancer treatments, which often have a low therapeutic ratio and require careful assessment of risks and benefits. Publication of registration trials should precede FDA approval to facilitate evaluation and implementation of new therapies. The timing of trial publication relative to FDA drug approvals has not been systematically investigated. Methods: We collected all FDA drug approvals for a cancer indication between 2000-19. Trials were identified using FDA labels as well as drugs and publications indexed on HemOnc.org. Approvals for generics/biosimilars, non-oncology indications and label revisions without supportive evidence were excluded. Dates of approval, the approval pathway, approval type (new vs expansion), and the first full publication related to the registration were recorded. Trials and approvals were matched using available metadata. We calculated the proportion of drugs approved prior to publication overall and for those receiving accelerated approval (AA). We used logistic regression to compare rates of pre-publication approval by approval pathway and by new vs expanded approval. Results: Among a total of 378 drug approvals, 139 (37%) had pre-publication approval. Of these, the median overall time from approval to publication was 140 days (IQR 64-281 days). For those with approval after publication, median time from publication to approval was 157 days (IQR 72-359 days). The number of drugs approved pre-publication rose by 27% between the first and last quarters of the study period, though, the proportion decreased as more anti-cancer drugs have been approved in recent years (Table). More drugs were approved pre-publication through AA than regular approval (46% vs 34%, OR 1.66 [95% CI 1.03-2.70], p=0.04) and as new approvals vs. expanded approvals (45% vs 32%, OR 1.76 [95% CI 1.15-2.70], p=0.01). Conclusions: A substantial minority of FDA approvals occur before trial results are published, with the odds being higher for drugs receiving AA and for new approvals. Since clinicians rely upon published results to inform risk/benefit decisions, efforts are needed to ensure trial results are published by the time of FDA approval of new cancer drugs and indications. [Table: see text]

Download Full-text

2006 RADAR Report Card on Conversion Rates from Accelerated FDA Approval to Regular FDA Approval for Drugs Used To Treat Hematologic Malignancies: Policy Changes Continue To Be Needed.

Blood ◽

10.1182/blood.v108.11.3318.3318 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3318-3318

Author(s):

Andrew J. Lurie ◽

Mark V. Mai ◽

Martin S. Tallman ◽

June McCoy ◽

Charles L. Bennett

Keyword(s):

Imatinib Mesylate ◽

Solid Tumors ◽

Trial Design ◽

Liposomal Doxorubicin ◽

Hematologic Malignancies ◽

Lymphocytic Leukemia ◽

Current Status ◽

Cancer Drugs ◽

Fda Approval ◽

Conversion Rates

Abstract Background: At ASH 2004 and 2005, we reported < 20% rates of from accelerated approval (AA) to regular approval (RA) for drugs used to treat hematologic malignancies (HMs). The FDA convened Oncologic Drug Advisory Committee (ODAC) meetings with sponsors of these drugs in 2003 and 2005 outlining recommendations for completion of subpart H trials. Congressmen Markey and Hinchey have raised concern over low rates of completion of subpart H studies for all AA drugs. The Research on Adverse Drug Events and Reports (RADAR) project reviewed the current status of subpart H commitments for all cancer drugs that received AA prior to 2005. Methods: NDAs and supplements for new uses from the FDA, package inserts, and literature reviews were reviewed. Results: Of 19 cancer drugs receiving AA prior to 2005, conversion to RA has occurred for 2 of 9 drugs for HMs and 8 of 11 drugs for solid tumors (STs) (22% vs 73%, p<0.05). Subpart H studies have been ongoing for a median of 5 years for AA drugs for HMs; however, for ST drugs, these studies were completed in a median of 2.5 years. Of 7 subpart H studies reviewed at the 2005 ODAC meeting on AA, subpart H evaluations continue for all 4 for HMs versus 1 of 3 for STs. HMs are characterized by lower rates of target populations, most having > 25,000 newly diagnosed patients annually (25% vs 78%). Recruitment targets are smaller for AA studies for HMs (median, 82 vs 295 patients) and subpart H studies (median, 295 vs 535). Conclusions: Rates of conversion from AA to RA remain poor for drugs for hematologic malignancies but not for solid tumors drugs. In spite of ODAC meetings and two congressional inquiries, little progress ahs been made towards completing these trials. RADAR continues to urge policy makers to modify the AA process for drugs used to treat hematologic malignancies. Hematologic malignancy drugs receiving AA prior to 2005 and current status of subpart studies Drug AA Indication Pts in AA trial design AA year Target # of pts in Subpart H study RA Year Imatinib mesylate CML 1027 2001 1027 2003 Bortezomib MM 202 2003 669 2005 Denileukin difitox* CTCL** 71 1999 195 Pending Liposomal cytarabine* Lymphomatous meningitis** 33 1999 195 Pending Gemtuzumab ozogamicin* AML** 142 2000 342 Pending Alemtuzumab* B-Cell Chronic lymphocytic leukemia** 93 2001 197 Pending Ibritumomab tiuxetan Certain NHLs ** 230 2002 293 Pending Imatinib mesylate CML (pedatrics)** 39 2003 35 Pending Tositumomab Certain NHLs** 60 2003 N/A Pending Solid tumor cancer drugs receiving AA prior to 2005 and current status of subpart studies Drug AA Indication Pts in AA trial design AA year Target # of pts in Subpart H study RA year * Recommendations for completing trials were made at recent ODAC meetings ** Indications with >25,000 new diagnosis annually Irinotecan Colorectal 304 1996 535 1998 Docetaxel Breast 134 1996 326 1998 Capecitabine Breast 163 1998 511 2001 Temozolomide Brain 162 1999 573 2005 Liposomal Doxorubicin* Ovarian 85 1999 474 2005 Oxaliplatin Colorectal 463 2002 795 2004 Anastrozole Breast 9366 2002 6196 2005 Gefitinib Lung 221 2003 1700 2005 Liposomal Doxorubicin* Kaposi’s sarcoma** 77 1995 250 Pending Amifostine Non-small cell lung** 25 1996 366 Withdrawn Imatinib mesylate GI stromal tumors** 147 2002 946 Pending

Download Full-text

Assessing Population Diversity in Phase III Trials of Cancer Drugs Supporting FDA Approval in Solid Tumors

International Journal of Cancer ◽

10.1002/ijc.33708 ◽

2021 ◽

Author(s):

Emre Yekedüz ◽

Dario Trapani ◽

Wenxin Xu ◽

Elisabeth GE Vries ◽

Chris Labaki ◽

...

Keyword(s):

Solid Tumors ◽

Population Diversity ◽

Phase Iii ◽

Cancer Drugs ◽

Fda Approval ◽

Phase Iii Trials

Download Full-text

Failure rate: Why many cancer drugs don't receive FDA approval, and what can be done about it

Cancer ◽

10.1002/cncr.28994 ◽

2015 ◽

Vol 121 (10) ◽

pp. 1529-1530 ◽

Cited By ~ 9

Author(s):

Carrie Printz

Keyword(s):

Failure Rate ◽

Cancer Drugs ◽

Fda Approval

Download Full-text

Dissemination of Information on Potentially Fatal Adverse Drug Reactions for Cancer Drugs From 2000 to 2002: First Results From the Research on Adverse Drug Events and Reports Project

Journal of Clinical Oncology ◽

10.1200/jco.2003.04.537 ◽

2003 ◽

Vol 21 (20) ◽

pp. 3859-3866 ◽

Cited By ~ 43

Author(s):

Lisa A. Ladewski ◽

Steven M. Belknap ◽

Jonathan R. Nebeker ◽

Oliver Sartor ◽

E. Allison Lyons ◽

...

Keyword(s):

Adverse Drug Reactions ◽

Adverse Drug Events ◽

Package Insert ◽

Clinical Findings ◽

Cancer Drug ◽

Cancer Drugs ◽

Journal Articles ◽

Drug Reactions ◽

Fda Approval ◽

First Results

Purpose: To describe the clinical findings, occurrence rates, causality evidence, and dissemination media for serious cancer drug–associated adverse drug reactions (ADRs) reported in the postmarketing setting. Methods: ADRs were termed serious if they resulted in death or severe organ failure. ADR information for oncology drugs from package insert (PI) revisions, so-called Dear Doctor letters, and journal articles was evaluated to identify serious ADRs reported from 2000 to 2002. Timing and content of information disseminated was assessed. Results: Twenty-five serious ADRs associated with 22 oncology drugs were identified after approval. Approximately half of these serious ADRs are associated with drugs approved before 1995. ADRs were described in articles in medical journals (17 ADRs), PI revisions (18 ADRs), and Dear Doctor letters (12 ADRs). PI revisions occurred less than 1 year after peer-reviewed publication for four ADRs. These revisions often differed for similar ADRs that occurred with drugs of the same class. Five of the seven ADRs lacking PI changes occurred with off-label use, for which PI change is not recommended by US Food and Drug Administration (FDA) policy. No cancer drug was withdrawn from the market during the observation period. Conclusion: Our findings demonstrate that serious ADRs may be discovered as long as 36 years after a drug receives FDA approval. This suggests a need for continued vigilance and efficient strategies for dissemination of information about ADRs associated with cancer drugs.

Download Full-text

REPORTING OF CARDIOVASCULAR EVENTS IN CLINICAL TRIALS SUPPORTING FDA-APPROVAL OF CONTEMPORARY CANCER DRUGS

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(19)32485-4 ◽

2019 ◽

Vol 73 (9) ◽

pp. 1879

Author(s):

Daniel Addison ◽

Janice Bonsu ◽

Lawrence Charles ◽

Avirup Guha ◽

Brandee Baker ◽

...

Keyword(s):

Clinical Trials ◽

Cardiovascular Events ◽

Cancer Drugs ◽

Fda Approval

Download Full-text

Pharmacogenomic Biomarkers in US FDA-Approved Drug Labels (2000–2020)

Journal of Personalized Medicine ◽

10.3390/jpm11030179 ◽

2021 ◽

Vol 11 (3) ◽

pp. 179

Author(s):

Jeeyun A. Kim ◽

Rachel Ceccarelli ◽

Christine Y. Lu

Keyword(s):

Precision Medicine ◽

Genomic Variation ◽

New Drugs ◽

Individual Response ◽

Cancer Therapies ◽

Cancer Drugs ◽

Fda Approval ◽

Us Fda ◽

Annual Proportion ◽

Clinical Adoption

Pharmacogenomics (PGx) is a key subset of precision medicine that relates genomic variation to individual response to pharmacotherapy. We assessed longitudinal trends in US FDA approval of new drugs labeled with PGx information. Drug labels containing PGx information were obtained from Drugs@FDA and guidelines from PharmGKB were used to compare the actionability of PGx information in drug labels across therapeutic areas. The annual proportion of new drug approvals with PGx labeling has increased by nearly threefold from 10.3% (n = 3) in 2000 to 28.2% (n = 11) in 2020. Inclusion of PGx information in drug labels has increased for all clinical areas over the last two decades but most prominently for cancer therapies, which comprise the largest proportion (75.5%) of biomarker–drug pairs for which PGx testing is required. Clinically actionable information was more frequently observed in biomarker–drug pairs associated with cancer drugs compared to those for other therapeutic areas (n = 92 (59.7%) vs. n = 62 (40.3%), p < 0.0051). These results suggest that further evidence is needed to support the clinical adoption of pharmacogenomics in non-cancer therapeutic areas.

Download Full-text