Targeted drug approvals in 2023: breakthroughs by the FDA and NMPA

According to the official website of China’s National Medicines and Pharmaceutical Administration (NMPA), a total of 87 novel drugs were approved in China in 2023, with targeted drugs accounting for 67.8% of the total, amounting to 59 drugs (Fig. 1a; Table 1) [https://www.nmpa.gov.cn/yaopin/ypjgdt/index.html]. Notably, domestic innovation is flourishing, with five first-in-class drugs, including Glumetinib, a c-Met inhibitor from Haihe Biopharma; Leritrelvir, a 3CL protease inhibitor from Raynovent; Anaprazole, a proton pump inhibitor from Xuanzhu Biopharm; Pegol-Sihematide, an EPO drug from Hansoh Pharma; and Zuberitamab from BioRay Biopharmaceutical Co., Ltd. Additionally, the world’s first allosteric inhibitor targeting TYK2, Sotyktu (deucravacitinib), has been approved for the treatment of psoriasis and Selumetinib, a MEK inhibitor co-developed by AstraZeneca and Merck Sharp & Dohme (MSD), became the first approved drug in China for the treatment of neurofibromatosis type I (NF1). Beyond these drugs, the approval of novel drug types such as CAR-T cell products, siRNA, monoclonal antibodies, dual antibodies, and ADCs in China is a significant development in the country’s pharmaceutical industry (Fig. 1a). Notably, Equecabtagene autoleucel, jointly developed by IASO Biotherapeutics and Innovent Biologics, became the first approved BCMA-targeted CAR-T cell therapy product in China. Additionally, Inaticabtagene autoleucel developed by Juventas was the first approved CAR-T cell therapy product in the field of leukemia treatment in China. In parallel, the acceleration in the rate of new drug approvals in China is also noteworthy. Glofitamab, for example, was approved in China only five months after its approval in the United States. Furthermore, numerous clinical trials for novel drugs are currently underway in China, and it is anticipated that these new medications will soon bring significant benefits to Chinese patients.

Fig. 1

NMPA and FDA-approved targeted drugs by modality, 2023. a Small molecules and protein-based drugs comprised a significant majority of NMPA approvals, while oligonucleotides only represented a single case. b The majority of FDA approvals for targeted drugs consist of small molecules and protein-based drugs, with small molecules being approved as new molecular entities (NMEs). Approved in four cases, oligonucleotides were also classified as new molecular entities (NMEs). Source: NMPA, FDA and Nature Reviews Drug Discovery (https://doi.org/10.1038/d41573-024-00001-x)

Table 1 Targeted drugs approved by the FDA and NMPA in 2023

During the year, the FDA’s Centre for Drug Evaluation and Research (CDER) approved 55 novel drugs, surpassing 37 in 2022 and second only to 59 in 2018¹, [https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2023]. Of these novel drugs, 47, or 85.5%, were targeted therapies, reflecting a clear trend towards more personalized and effective treatment options. Within this category, 26 were small molecules, 8 were monoclonal antibodies, 4 were bispecific antibodies, 3 were recombinant fusion proteins, 4 were small nucleic acid drugs (including 2 antisense oligonucleotides, 1 RNA aptamer, and 1 siRNA), and 2 were synthetic peptide analogs (Fig. 1b; Table 1). The targets of these new drugs span a range of biological processes, including kinases, cytokines, enzymes, receptors, ion channels, and proteasomes. This diversity highlights the ongoing efforts to develop innovative therapies that target the root causes of various diseases. In terms of indications approved for marketing, cancer remains the leading focus of research and development, with 14 new cancer therapies, representing 29.7% of the total. Immune system disorders followed closely behind, accounting for 8 approved therapies (17%) while neurological disorders ranked third, with 7 approved therapies (14.9%). Diseases of the blood and lymphatic system, endocrine and metabolic diseases, and infectious diseases each accounted for four cases (8.5%) (Fig. 1b). This distribution highlights the diverse range of therapeutic areas targeted by novel drug development. Notably, there has been a gradual increase in targeted therapeutics for rare diseases, such as Pompe’s disease and paroxysmal sleep hemoglobinuria. These diseases often lack effective treatment options, making the development of targeted therapies particularly important for improving patient outcomes. Overall, the data presented in this article highlights the significant progress being made in the field of drug development, with a particular emphasis on targeted therapies. The increasing approval of novel drugs offers hope to patients with various diseases, and further research and development is expected to lead to even more effective and personalized treatment options in the future.

It is heartening to observe that the FDA has granted approved three innovative Chinese new drugs: Loqtorzi (toripalimab), Fruzaqla (fruquintinib) and Ryzneuta (efbemalenograstim). Toripalimab is a monoclonal antibody targeting PD-1, marks the first FDA-approved drug for the treatment of nasopharyngeal cancer. Fruquintinib, approved for the treatment of metastatic colorectal cancer, is unique as the first and only highly selective inhibitor approved in the U.S. for comprehensive inhibition of all three VEGF receptor kinases, regardless of a patient’s biomarker status. Efbemalenograstim, approved for the treatment of neutropenia in oncology patients receiving anti-cancer drugs, stands out as the only long-acting G-CSF (granulocyte colony-stimulating factor) product approved in both China and the U.S., showcasing its global relevance and potential impact on patient care². As a result, Yifan Pharmaceutical Co., Ltd. has become the first innovative biopharmaceutical company in China to be approved by the FDA as a Marketed Access Holder (MAH), marking a significant milestone in the company’s journey towards global leadership in biopharmaceutical innovation.

Innovation in mechanism-based therapies reached new heights in the past year, with numerous drugs earning the distinction of “First-In-Class". These groundbreaking therapies either represent the first treatment option for a specific disease or introduce a novel mechanism of action. One remarkable example is Daprodustat, the first oral drug approved by the FDA for the treatment of anemia with chronic kidney disease (CKD) in dialysis patients³. Daprodustat reversibly inhibits HIF-PH1/2/3, thereby increasing HIF levels. This, in turn, stimulates the expression of genes essential for red blood cell production, such as EPO and VEGF. Another notable development is the approval of Fezolinetant, the world’s first non-hormone targeted drug, for the treatment of moderate to severe hot flashes caused by menopause. Unlike hormonal drugs commonly used to manage these symptoms, Fezolinetant works primarily by antagonizing the neurokinin-3 (NK3) receptor which offers patients a better quality of life with fewer side effects and more pronounced therapeutic effects.

Furthermore, 2023 marked a significant milestone in gene therapy with the approval of four groundbreaking nucleic acid drugs. Among them, Qalsody (tofersen) stands out as the first and currently only gene therapy designed to target the underlying pathogenesis of amyotrophic lateral sclerosis (ALS). Tofersen, an antisense oligonucleotide (ASO), specifically targets mRNA produced by the SOD1 mutant gene, halting the production of the toxic SOD1 protein and slowing the progression of ALS. Another noteworthy ASO therapy, Wainua (eplantersen), has been approved for marketing to inhibit the production of the TTR protein for the treatment of both hereditary and non-hereditary amyloidosis polyneuropathy. This innovative approach utilizes antisense oligonucleotide ligand coupling (LICA) technology, coupling ASO drugs to ligand molecules that bind to specific receptors on the cell surface. In addition, Izervay (avacincaptad pegol) represents a novel complement C5 protein inhibitor and the second FDA-approved RNA aptamer⁴. The approval of Avacincaptad pegol signifies the emergence of a potentially transformative innovator in the field of Geographic Atrophy (GA). Lastly, Rivfloza (nedosiran) was approved by the FDA in September 2023 as the second siRNA drug worldwide for the treatment of primary hyperoxaluria type 1 (PH1). This latest development showcases the increasing impact of gene therapy in treating previously intractable diseases and offers new hope for patients suffering from debilitating conditions.

In the realm of antibody therapeutics, we have witnessed the emergence of four groundbreaking bispecific antibodies capable of binding to two distinct epitopes or antigens simultaneously. This unique dual-action mechanism enhances target specificity, paving the way for innovative immunotherapy advancements. Notable examples include the Epcoritamab and Glofitamab, which target both CD20 and CD3, showcasing the potential of this approach in treating a range of diseases.

Targeted therapies continue to constitute the majority of approved therapies worldwide. However, immunotherapy has emerged as a significant avenue in cancer treatment in recent years, particularly when combined with targeted therapies, leading tosuperior therapeutic outcomes. This combination intervenes in the tumor’s immune escape mechanisms, thereby enhancing the immune cells’ attack capabilities and ultimately enhancing the efficacy of immunotherapy. Future advancements in targeted therapies will involve the identification and development of novel targets that specifically target immune escape mechanisms and interfere with immune cell-tumor interactions to improve immunotherapy effectiveness. Furthermore, the utilization of technologies such as RNA interference, gene editing, and other intracellular targeting methods will enable more precise therapeutic strategies.

In 2024, Signal Transduction and Targeted Therapy will continue to push the boundaries of targeted therapies, introducing innovative and disease-focused solutions. With a strong focus on clinical research, our aim is to publish more groundbreaking papers on novel therapeutic targets, signaling pathways, and effective new therapies especially drug discovery with clinical applications.