In a significant development, the US Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) approved 55 new drugs in 2023. This marks the second-highest count in the past 30 years, with the highest being 59 new drug approvals in 2018 and represents an impressive 50% increase in drugs approved in 2022.
However, although 55 new drugs is a significant amount, it is relatively small considering the staggering nine out of ten drug candidates that fail during clinical trials and drug approval. That's not to mention the drug candidates that don't advance through discovery and the preclinical stage, which brings the overall rate of failure for drug discovery and development to over 90%.
Drug Discovery and Development: Stages, Failure Rates, and Improvement Strategies
Figure. 1: Overview of drug discovery and development stages and their failure rates. [Adapted from: Sun D, Gao W, Hu H, Zhou S. Why 90% of clinical drug development fails and how to improve it? Acta Pharm Sin B. 2022 Jul;12(7):3049-3062
Over the years, R&D scientists have implemented many successful strategies to improve each drug discovery and development stage. Yet, the overall success rate of clinical drug development still needs to improve. But why do most drugs fail?
Despite promising preclinical data, most drugs fail in clinical development for two main reasons:
- Poor clinical efficacy
- Unmanageable toxicity
Initial research, screening, and preclinical trials involving lab-based in vitro and in vivo testing determine which drugs are safe and effective enough to take forward. Thus, the key to success in clinical drug development lies in these early stages: target identification and validation, drug candidate selection and optimization, and the careful balance of clinical dose, efficacy, and toxicity.
For example, good target identification and validation can increase confidence in the relationship between the target, disease, and normal tissue, as well as explore target engagement and determine whether target modulation will lead to mechanism-based side effects. In addition, drug optimization that gives equal weight to drug potency/specificity, drug tissue exposure/selectivity, and the dose required to balance clinical efficacy/toxicity improves drug candidate selection and clinical dose optimization.
Typically, new drugs take over a decade and cost more than $1 billion to develop. Given the high drug development failure rates, advancing a drug candidate to a phase I clinical trial requires a relentless quest for innovation. It is a considerable achievement for any pharmaceutical company or academic research facility.
This article shares those successes within oncology drug development in 2023, the trends and setbacks, and what’s on the horizon in 2024.
Novel oncology drugs approved by the FDA in 2023
In 2023, the FDA approved 13 novel anti-cancer therapies. Here’s an overview of these innovative new options.
Table: Novel oncology drugs approved in 2023
| Trade name |
Drug | Maker | Type of drug |
Indication | When approved |
Further information |
|---|---|---|---|---|---|---|
| Augtyro | repotrectinib | Bristol Myers Squibb |
ROS-1 inhibitor |
Non small-cell lung cancer |
November 15 |
The first ROS1 inhibitor to be approved to treat patients whose tumors did not respond to or relapsed following treatment with a previous ROS1 inhibitor |
| Columvi | glofitamab-gxbm | Genentech | BiTE | Certain types of diffuse large B-cell lymphoma (DLBCL) or large B-cell lymphoma (LBCL) |
June 15 |
For patients who have received two or more lines of therapy |
| Elrexfio | elranatamab-bcmm | Pfizer | BiTE | Relapsed or refractory multiple myeloma |
August 14 |
For adults who have received at least four prior lines of therapy |
| Epkinly | epcoritamab-bysp | Monograph | BiTE | Relapsed or refractory diffuse large B-cell lymphoma (not otherwise specified) and high-grade B-cell lymphoma |
May 19 |
For patients who have received two or more lines of therapy |
| Fruzaqla | fruquintinib | Takeda | TKI | Refractory, metastatic colorectal cancer |
November 8 |
|
| Jaypirca | pirtobrutinib | Eli Lilly |
BTK inhibitor |
Relapsed or refractory mantle cell lymphoma |
January 27 |
For adults who have had at least two lines of systemic therapy, including a BTK inhibitor |
| Loqtorzi | toripalimab-tpzi | Coherus BioSciences |
PD-1 inhibitor |
Recurrent or metastatic nasopharyngeal carcinoma |
October 27 |
Used with or following other therapies |
| Ogsiveo | nirogacestat | SpringWorks Therapeutics |
Suppresses notch signalling |
Progressing desmoid tumors |
November 27 |
|
| Orserdu | elacestrant | Menarini Group |
SERD | Estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated, advanced or metastatic breast cancer with disease progression |
January 27 |
For patients who have had at least one line of endocrine therapy |
| Talvey | talquetamab-tgvs | Johnson & Johnson |
BiTE | Relapsed or refractory multiple myeloma |
August 9 |
For adults who have received at least four prior therapies |
| Truqap | capivasertib | AstraZeneca | TKI | Breast cancer that meets certain criteria |
November 16 |
|
| Vanflyta | quizartinib | Daiichi Sankyo |
TKI | Newly diagnosed acute myeloid leukemia that meets certain criteria |
July 20 |
For use as part of a treatment regimen |
| Zynyz | retifanlimab-dlwr | Incyte | ICI | Metastatic or recurrent locally advanced Merkel cell carcinoma |
March 22 |
The trends and setbacks in oncology drug approvals in 2023
In 2023, we saw significant oncological advancements in the treatment of hematologic malignancies, with the FDA approval of talquetamab-tgvs (Talvey) and elranatamab-bcmm (Elrexfio), both new bispecific T cell-engaging antibodies, in relapsed/refractory multiple myelomas.
The FDA approved four new bispecific T cell-engaging antibodies (BiTEs) and a raft of new small-molecule therapies. However, although many antibody-drug conjugates (ADCs) have been approved in recent years, they were absent from the new oncology drug approvals list in 2023.
BiTEs (Bispecific T cell engagers):
First proposed in the 1960s, this class of oncology drugs utilizes a patient’s immune system to fight cancer cells. The four FDA approvals in 2023 brought the total number of BiTEs to seven.
Small-molecule drugs:
These include targeted therapies like kinase inhibitors that are small enough to enter individual cells to deliver targeted treatments. Small-molecule drugs proved a real success story for 2023, with eight novel small-molecule drugs receiving FDA approval for oncology indications.
ADCs (Antibody-drug conjugates):
These drugs deliver chemotherapy to cancer cells without harming healthy cells in the body. First approved in 2000, over a dozen ADC types are available, Although 2023 did not witness the emergence of new ADC types as seen in previous years, the field is now characterized by evolving strategies for this class of therapeutics.
Despite this exciting progress, the year was not without its setbacks. Apart from general financial challenges in 2023 combined with the lasting effects of trial disruptions, which impeded therapeutic progress during the pandemic, the development of anti-CD47 antibodies was affected by the closure of developers and the shelving of development programs following concerns over safety and efficacy. Once considered a promising drug candidate to boost chemotherapy in the treatment of blood cancers,new strategies are emerging its future now looks uncertain.
In February, Gilead announced it had discontinued its study of magrolimab in acute Myeloid Leukemia. And in the same month, Arch Oncology also ended work on an anti-CD47 antibody before closing its offices. Similarly, AbbVie pulled out of co-development of anti-CD47 drug candidate lemzoparlimab with I-Mab and ALX Oncology ended its programs in MDS and AML after poor results.
What can we expect from oncological drug development in 2024?
The FDA issued 14 oncology approvals in the first quarter of 2024, including the first tumor-infiltrating lymphocyte (TIL) cell therapy to reach the market.
- Lifileucel (Amtagvi) is a new immunotherapy indicated for treating adult patients with unresectable or metastatic melanoma. It is the first cancer treatment that uses immune cells called tumor-infiltrating lymphocytes (TILs).
- Like CAR T-cell therapy, lifileucel is made using a patient’s T cells. However, unlike CAR T-cell therapy, in which T cells are collected from the patient’s circulating blood, TIL therapy uses T cells collected from the patient’s tumor.
April was another excellent month for oncology therapies receiving FDA approval for diseases including HER2-positive solid tumors, early-stage non-small cell lung cancer (NSCLC), multiple myeloma, and other cancer types. May saw the earlier-than-expected approval of tarlatamab for treating advanced small-cell lung cancer (SCLC). Tarlatamab is an investigational, first-in-class, bispecific T cell engager designed to target DLL3 on SCLC cells and CD3 on T cells.
Looking ahead, oncology drug development trends from the last couple of years are set to continue, with more therapies coming from emerging companies—up to 71% in 2022 from 51% in 2017 . And, increased numbers of drugs being developed in non-US countries, with China and Japan leading the charge for worldwide innovation.
The pharmaceutical and biopharmaceutical industries recognize the overwhelming need to accelerate the drug discovery process and increase drug development success rates. With this in mind, they are embracing recent advances in artificial intelligence (AI), cutting-edge chemical technology, and small-molecule chemical probes and tools, determined to improve failure rates and ultimately increase the number and range of therapies available to patients. It will be interesting to see how these technological and scientific advancements impact the success rates for drug discovery and development in the years to come.
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