Oncology Regulatory Review 2023
The OCE collaborates with three FDA product centers reviewing drugs, biologic therapies, and devices to develop and execute an integrated regulatory approach to enhance the cross-center coordination of oncology product clinical review. Several of OCE's regulatory programs and projects addressing important topics also provide short annual updates below.
Jump to:
- Drugs and Biologic Therapies: CDER
- Cellular Cancer Therapies: CBER
- 2023 Oncology Approvals Table
- Oncology Devices: CDRH
OCE Regulatory Programs:
- Project Orbis
- Pediatric Oncology Program
- Rare Cancers Program
- Oncology Labeling Program
- Project Renewal
- Project Confirm
Drugs and Biologic Therapies: Office of Oncologic Diseases, CDER
The Office of Oncologic Diseases (OOD) in the Center for Drug Evaluation and Research (CDER) approved 13 novel drugs (new medical entities or biologics) for treatment of various types of cancer including colorectal, prostate, lung and low-grade gliomas. Among the novel drug approvals were three first-in-class entities—drugs with mechanisms of action different from those of existing therapies:
- Talquetamab-tgvs injection (Talvey) to treat adults with refractory or relapsed multiple myeloma who have received other therapies.
- Nirogacestat (Ogsiveo) for adults with progressing desmoid tumors who require systemic treatment. This is the first FDA-approved treatment for desmoid tumors.
- Capivasertib (Truqap) with fulvestrant for adults with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer with one or more PIK3CA/AKT1/PTEN-alterations, as detected by an FDA-approved test.
OOD also completed 67 other approval decisions to expand the use or patient population of previously approved drugs. Several therapies were approved for various pediatric and rare cancers (see sections below). OOD clinical reviewers published an article describing the 2023 oncology approvals: Highlights of FDA Oncology Approvals in 2023: Bispecific T-cell Engagers, Pediatric Indications, and Inclusive Drug Development (covering approvals from November 8, 2022, to October 6, 2023).
Cellular Cancer Therapies: CBER
The Center for Biologics Evaluation and Research (CBER) reviews and regulates cellular cancer therapies in partnership with OCE.
In 2023, CBER and OCE approved one new cellular therapy product for hematologic malignancy in 2023, omidubicel-only (OMISIRGE). The product is approved to reduce the time to neutrophil recovery and the incidence of infection in adults and children receiving umbilical cord blood transplants following myeloablative conditioning as treatment for hematologic malignancies. CBER and OCE also approved an efficacy supplement for axicabtagene ciloleucel (Yescarta), and a safety supplement for brexucabtagene autoleucel (Tecartus).
2023 CDER and CBER Oncology Approvals
|
NMEs/Original BLA
|
14 (13 CDER, 1 CBER)
|
| Supplements (new indication) | 42 (42 CDER, 0 CBER) (2 RTOR, 26 AAid) |
| Supplements (new population) | 9 (9 CDER, 0 CBER) (2 RTOR, 4 AAid) |
|
Supplements (other) |
2 (CBER) |
| 505b2 | 15 |
| Biosimilars | 1 |
| Total Approvals | 83 |
|
|
|
|
|
|
AAid: Assessment Aid; BLA: Biologics License Application; NME: new molecular entity; RTOR: Real-Time Oncology Review.
Oncology Devices: CDRH
The Center for Devices and Radiological Health (CDRH) reviews and regulates oncology devices, including in vitro diagnostics (IVDs), in partnership with OCE. In 2023 CDRH in collaboration with OCE authorized 118 oncology devices including 61 IVDs, with 26 IVDs having new indications and of those 15 having new companion diagnostic indications. Additionally, 41 radiation oncology and diagnostic imaging devices were authorized as well as other oncology devices including: breast cancer sentinel lymph node identification, tumor ablation, biopsy, soft tissue markers, and orthopedic devices. Some of the pre-market submission highlights include:
- Invitae Common Hereditary Cancers Panel De Novo, the first authorization for a qualitative high-throughput sequencing based in vitro diagnostic test system intended for analysis of germline human genomic DNA extracted from whole blood for detection of substitutions, small insertion and deletion alterations, and copy number variants in a panel of targeted genes. This test system is intended to provide information for use by qualified health care professionals, in accordance with professional guidelines, for hereditary cancer predisposition assessment and to aid in identifying hereditary genetic variants potentially associated with a diagnosed cancer.
- Over the counter 23andMe Personal Genome Service Cancer Predisposition Genetic Health Risk Report for BRCA1/BRCA2 (Selected Variants) to expand the number of BRCA1/2 variants detected to 44 and cleared a predetermined change control plan to add more BRCA1/BRCA2 variants without the need for additional premarket review.
- EasySep Human Bone Marrow CD138 Positive Selection Kit intended to enrich CD138+ cells from bone marrow collected from patients diagnosed with multiple myeloma.
- Bladder EpiCheck Kit, which detects a novel biomarker for bladder cancer monitoring. The kit is intended for the qualitative detection of DNA methylation patterns of 15 loci in human DNA (from urine specimens) that are associated with transitional cell carcinoma of the bladder. It is indicated for use as a non-invasive method to monitor for tumor recurrence in conjunction with cystoscopy in patients previously diagnosed with non-muscle invasive bladder cancer.
- Idylla MSI Test, an IVD that detects a novel microsatellite instability biomarker. The text detects seven monomorphic biomarkers (ACVR2A, BTBD7, DIDO1, MRE11, RYR3, SEC31A and SULF2) and is indicated for the qualitative identification of microsatellite instability in colorectal cancer tumors, indicative of mismatch repair deficiency, and as an aid in the identification of probable Lynch syndrome to help identify patients that would benefit from additional genetic testing to diagnose Lynch syndrome.
- BRAHMS CgA II Kryptor an IVD to measure Chromogranin A in human serum and used as an aid in monitoring of disease progression in patients with gastroentero-pancreatic neuroendocrine tumors (GEP-NETs, grade 1 and grade 2).
- Elecsys Tg II an IVD to measure Thyroglobulin to use an aid in monitoring for the presence of persistent or recurrent/metastatic disease in patients who have differentiated thyroid cancer and have had thyroid surgery (with or without ablative therapy).
- RefleXion Medical Radiotherapy System, a combination linear accelerator and positron emission tomography system that can treat targets in lung and bone using biology-guided radiation therapy.
- P-Cure Proton Beam Therapy System, a new proton system that can deliver a proton beam to targets in the head, neck, and thorax in patients that are in a seated position.
- HistoSonics Edison System for the non-invasive destruction of liver tumors, including unresectable liver tumors, using a non-thermal, mechanical process of focused ultrasound. This is a novel ablation method that generates cavitation and differs from high-intensity focused ultrasounds which uses heat to destroy tissue.
In March 2023, FDA issued two safety communication updates, UPDATE: Reports of Squamous Cell Carcinoma (SCC) in the Capsule Around Breast Implants, sharing information from the FDA's review of literature and medical device reports about SCC in the capsule around breast implants. FDA informed health care providers that they can now submit case reports of SCC, various lymphomas, and any other cancers in the capsule around breast implants to the Patient Registry and Outcomes for Breast Implants and Anaplastic Large Cell Lymphoma (ALCL) Etiology and Epidemiology (PROFILE).
CDRH held an advisory panel meeting on November 29 on the design of multi-cancer detection (MCD) in vitro diagnostic devices as well as potential study designs and study outcomes of interest that could inform the assessment of the probable benefits and risks of MCD screening tests. The committee’s discussion and recommendations from this meeting will help inform future Agency regulatory efforts for these novel tests.
Project Orbis remains an active OCE program with 19 unique approvals in 2023. In addition, OCE sought to expand interactions with existing regulatory partners. FDA Oncology has collaborated with the European Medicines Agency (EMA) and Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) since 2004 and 2014, respectively, via a monthly teleconference involving six regulatory health authorities.
In May 2023, an FDA OCE delegation traveled to EMA in Amsterdam, Netherlands. A visit to PMDA in Tokyo, Japan, followed in November 2023. During these visits, the agencies discussed expanding regulatory cooperation into other areas of oncology drug development, including EMA and PMDA joining Project Orbis as observers. OCE will focus on cultivating these new areas of collaboration with EMA and PMDA in 2024.
FDA approved the following drug-indication combinations through Project Orbis in 2023. Visit Oncology (Cancer)/Hematologic Malignancies Approval Notifications for further information on these approvals.
|
Approval Date |
Product Name(s) |
Indication |
Orbis # |
AAid |
RTOR |
AA cRA |
|
|---|---|---|---|---|---|---|---|
|
1. |
Tukysa (tucatinib) |
RAS WT HER2+ mCRC |
84 |
Y |
N |
Y - AA |
|
|
2. |
Keytruda (pembrolizumab) |
adjuvant NSCLC |
80 |
Y |
N |
N |
|
|
3. |
Trodelvy (sacituzumab govitecan-hziy) |
HR+, HER2-, mBC |
89 |
Y |
N |
N |
|
|
4. |
Tafinlar (dabrafenib) + Mekinist (trametinib)1 |
BRAF-V600E mutation LGG |
78 |
Y – Orig N - Supps |
N |
N |
|
|
5. |
Columvi (glofitamab-gxbm)2 |
3L+ DLBCL |
85 |
Y |
N |
Y - AA |
|
|
6. |
6.20.20233 |
Blincyto (blinatumomab)1 |
CD19+ B-cell precursor ALL |
73 |
Y |
Y |
Y - cRA |
|
7. |
Jemperli (dostarlimab-gxly) |
primary advanced or recurrent EC that is dMMR, or MSI-H |
99 |
Y |
N |
N |
|
|
8. |
Talvey (talquetamab-tgvs)2 |
RRMM, at least 4 prior therapies |
86 |
Y |
N |
Y - AA |
|
|
9. |
Elrexfio (elranatamab-bcmm)2 |
RRMM, at least 4 prior therapies |
90 |
Y |
N |
Y - AA |
|
|
10. |
Opdivo (nivolumab) |
adjuvant melanoma |
88 |
Y |
N |
N |
|
|
11. |
Loqtorzi (toripalimab-tpzi)2 |
NPC |
43 |
Y |
N |
N |
|
|
12. |
Keytruda (pembrolizumab) |
BTC |
101 |
Y |
N |
N |
|
|
13. |
Fruzaqla (fruquintinib)2 |
mCRC, after fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy; an anti-VEGF therapy |
107 |
N |
Y |
N |
|
|
14. |
Augtyro (repotrectinib)2 |
ROS1+ mNSCLC |
103 |
Y |
Y |
N |
|
|
15. |
Keytruda (pembrolizumab) |
1L HER2- Gastric and GEJ |
91 |
Y |
N |
N |
|
|
16. |
Truqap (capivasertib)2 |
HR+ HER2- locally advanced or mBC |
92 |
Y |
Y |
N |
|
|
17. |
Xtandi (enzalutamide)1 |
nmCSPC |
102 |
Y |
Y |
N |
|
|
18. |
Iwilfin (eflornithine) |
Neuroblastoma (pediatric) |
87 |
Y |
Y |
N |
|
|
19. |
Padcev (enfortumab vedotin-ejfv)1 + Keytruda (pembrolizumab)1 |
la/mUC |
117 |
Y |
Y |
Y - cRA |
- Two or more separate applications associated with approval.
- New Molecular Entity (NME) or new/original biologic.
- No OCE approval announcement issued.
The OCE Pediatric Oncology Program works to promote the development of new safe and effective drugs and biologics to treat cancer in children and adolescents. With the authority granted by the Pediatric Research Equity Act (PREA), the OCE Pediatric Oncology Program aims to increase the number and timeliness of molecularly targeted pediatric cancer investigations for certain new targeted therapies under development for treatment of adult cancers.
This program also leverages the authority under the Best Pharmaceuticals for Children Act (BPCA) to encourage voluntary conduct of pediatric trials of new cancer drugs and biologics much earlier in the development timeline by issuing Written Requests for these studies. The Pediatric Oncology Program also provides community outreach and works with a variety of international stakeholders to facilitate timely global pediatric cancer drug development programs.
In 2023, there were 11 approvals of 7 different drugs and biologics to treat pediatric patients with cancer. Notable approvals include:
- Eflornithine to reduce the risk of relapse in pediatric and adult patients with high-risk neuroblastoma.
- Dabrafenib and trametinib in combination for the treatment of pediatric patients 1 year of age and older with low grade glioma harboring a BRAF V600E mutation who require systemic treatment.
- New pediatric formulations of entrectinib, dabrafenib, and trametinib for patients unable to swallow tablets or capsules.
See OCE Pediatric Oncology Drug Approvals for more information.
| Initial Pediatric Study Plans (iPSPs) and Written Requests 2023 | |
| Type F Meetings to discuss iPSPs prior to submission | 6 |
| iPSPs reviewed | 103 |
| Agreed iPSPs issued | 95 |
| Amended Agreed iPSPs issued | 11 |
| Proposed Pediatric Study Requests reviewed | 16 |
| Written Requests issued | 4 |
Launched in late 2021, the OCE Rare Cancers Program aims to leverage OCE’s ongoing initiatives to promote development of safe and effective new drugs and biologics to treat patients with rare cancers.
In conjunction with Project Community, the Rare Cancers Program participated in a Conversations on Cancer discussion, “Beginning the Rare Cancer Journey: Charting the Best Path to an Accurate Diagnosis,” to increase public awareness regarding the challenges to receiving a timely, correct diagnosis experienced by some patients with rare cancers and encourage dialogue to mitigate these challenges.
Other outreach activities in 2023 included participation in a Project Community Quarterly Advocacy Meeting with patients with rare cancers, and in programming related to rare cancer drug development during FDA Rare Disease Day.
As discussed during an initial public transparency meeting held in August, the Rare Cancers Program is working with OCE’s Project Catalyst, the Foundation for the National Institutes of Health, and the National Cancer Institute to form a public- private partnership to develop new anti-cancer therapies for ultra-rare cancers.
Notable Office of Oncologic Diseases 2023 approvals of drugs or biologics for rare cancers or other rare diseases included:
- Nirogacestat for the treatment of patients with progressing desmoid tumors.
- Ivosidenib for the treatment of adult patients with relapsed/refractory myelodysplastic syndromes with an IDH1 mutation.
- Dabrafenib/trametinib for pediatric patients with BRAFV600E mutant low-grade glioma.
- Eflornithine for the treatment of pediatric patients with high-risk neuroblastoma.
In 2023, the Oncology Labeling Program:
- Served as the core team for the FDA Draft Guidance for QTc Information in Human Prescription Drug and Biologic Product Labeling (August 2023)
- Served with the core cross center teams for 2 FDA key labeling guidance documents related to safe use that were published in 2023:
- FDA Guidance for the Dosage and Administration Section of Labeling (January 2023)
- Labeling for Dosing Based on Weight or Body Surface Area for Ready-to-Use Containers—“Dose Banding” (October 2023)
- Participated in the development and clearance of 4 FDA draft labeling guidance documents planned for publication by FDA in 2023-2024 (in clearance):
- Draft Drug Interactions Section of Labeling for Human Prescription Drug and Biological Products—Content and Format
- Draft Combined Hormonal Contraceptives for Prevention of Pregnancy—Labeling for Health Care Providers and Patients
- Updated Labeling for Biosimilar and Interchangeable Biosimilar Products
- Draft Pharmacokinetics in Patients with Impaired Hepatic Function—Study Design, Data Analysis, and Impact on Dosing and Labeling; Revised Draft
- Advanced oncology labeling awareness through engagement with the external community and key stakeholders by presenting at the 2023 Global Labeling and Regulatory Symposium and at the 2023 FDA-ASH Regulatory Workshop.
- Core review team for Project Renewal to ensure the use of published data is translated accurately into clinically meaningful and scientifically up to date drug information in labeling.
- Collaborated across FDA Centers on two Citizen’s Petitions resulting in labeling revisions to improve the safe use of oncology products for cancer patients.
- Collaborated across FDA Centers for drug interactions with food, drug disposal information, and dosing of patients with organ impairment where these intersect with oncology product labeling.
Since its launch in 2018, Project Renewal has updated two long-standing, off-patent oncology drug labels as part of OCE’s ongoing public health commitment.
Multidisciplinary teams of FDA review staff, practicing oncologists, hematology/oncology fellows in training, oncology pharmacists, and other scientific staff review the publicly available data that informs the safe and effective use of older oncology drugs. Ultimately, FDA oncologists independently review the available data to ensure revised labeling provides adequate directions for contemporary use.
In 2023, Project Renewal:
- Approved the updated labeling for Temodar on September 14, 2023, under six supplemental NDAs.
- As of the end of 2023, 14 NDA supplements have been filed and approved under Project Renewal.
- Initiated review of additional oncology products, including evaluating 8 potential new or updated uses.
- Collaborated with FDA Office of Generic Drugs to update generic oncology product labeling under the Making Objective Drug Evidence Revisions for New (MODERN) Labeling Act.
- Expanded collaborations with a division in FDA Office of New Drugs to assist in the updated labeling of non-oncologic drugs.
Six academic oncologists and 5 clinical fellows from 11 institutions across the US participated in labeling evaluation as part of our on-going effort to improve awareness and education of FDA and product labeling. Thirteen oncologists and fellows who participated in Project Renewal also have participated in additional OCE educational efforts including the FDA-AACR Oncology Educational Fellowship.
Project Confirm, begun in October 2021, is an OCE initiative to increase the transparency of outcomes related to accelerated approval for oncology indications.
The cornerstone of Project Confirm is a searchable public database updated in real-time, listing all accelerated approvals granted in oncology since 1992. The database is divided into separate pages that list accelerated approvals that are ongoing, those that have verified clinical benefit and have been granted traditional approval, and those that have been withdrawn. The project aims to continue to facilitate evaluation of ongoing accelerated approvals and to continue efforts to increase public awareness of the program and its outcomes.
In 2023, Project Confirm supported internal projects including FDA's efforts related to the implementation of accelerated approval provisions described in the recent Food and Drug Omnibus Reform Act legislation, as well as external discussions, presentations, and publications on the accelerated approval program.