The Pharmaceutical Industry in 2024: An Analysis of the FDA Drug Approvals from the Perspective of Molecules
Beatriz G. de la Torre, Fernando Alberício
Research Article — Peer-Reviewed Source
Original research published by Torre et al. in Molecules. Redistributed under Open Access — see publisher for license terms. MedTech Research Group provides these references for informational purposes. We do not conduct original research. All studies are the work of their respective authors and institutions.
The U.S. Food and Drug Administration (FDA) has authorized 50 new drugs in 2024, which matches the average figure for recent years (2018-2023). The approval of 13 monoclonal antibodies (mAbs) sets a new record, with these molecules accounting for more than 25% of all drugs authorized this year. Three proteins have been added to the list of biologics, and with the inclusion of four TIDES (two oligonucleotides and two peptides), only one in three approved drugs this year is a small molecule. As of 2023, no antibody-drug conjugates (ADCs) have reached the market this year. Two deuterated drugs have been approved, bringing the total approvals for this class of compounds to four. This year saw the authorization of two more PEGylated drugs-both peptides-highlighting a renewed interest in this strategy for extending drug half-life, despite the setback caused by the withdrawal of peginesatide from the market in 2014 due to adverse side effects. <i>N</i>-aromatic heterocycles and fluorine atoms are present in two-thirds of all the small molecules approved this year. Herein, the 50 new drugs authorized by the FDA in 2024 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins), TIDES (oligonucleotides and peptides), combined drugs, natural products, F-containing molecules, nitrogen aromatic heterocycles, aromatic compounds, and other small molecules.
Abstract
The U.S. Food and Drug Administration (FDA) has authorized 50 new drugs in 2024, which matches the average figure for recent years (2018–2023). The approval of 13 monoclonal antibodies (mAbs) sets a new record, with these molecules accounting for more than 25% of all drugs authorized this year. Three proteins have been added to the list of biologics, and with the inclusion of four TIDES (two oligonucleotides and two peptides), only one in three approved drugs this year is a small molecule. As of 2023, no antibody-drug conjugates (ADCs) have reached the market this year. Two deuterated drugs have been approved, bringing the total approvals for this class of compounds to four. This year saw the authorization of two more PEGylated drugs—both peptides—highlighting a renewed interest in this strategy for extending drug half-life, despite the setback caused by the withdrawal of peginesatide from the market in 2014 due to adverse side effects. N -aromatic heterocycles and fluorine atoms are present in two-thirds of all the small molecules approved this year. Herein, the 50 new drugs authorized by the FDA in 2024 are analyzed exclusively on the basis of their chemical structure. They are classified as the following: biologics (antibodies, proteins), TIDES (oligonucleotides and peptides), combined drugs, natural products, F-containing molecules, nitrogen aromatic heterocycles, aromatic compounds, and other small molecules.
1. Analysis
During 2024, the U.S. Food and Drug Administration (FDA) has approved 50 new drugs [ 1 ]. This figure matches the average of 50 per year for the period 2018–2023 ( Figure 1 ), reaffirming that the COVID-19 pandemic has not significantly impacted the pharmaceutical industry. On the contrary, analysts believe that the industry’s rapid response in developing vaccines has helped boost public confidence in the pharmaceutical sector. Closer inspection of the 50 drugs approved in 2024 by type of molecule reveals 16 biologics (17, 10, 13, 14, 15, and 17 in 2018, 2019, 2020, 2021, 2022, and 2023, respectively), 4 TIDES (2 oligonucleotides and 2 peptides in 2024 vs. 3 and 1 in 2018, 2 and 3 in 2019 and 2020, 2 and 8 in 2021, 1 and 4 in 2022, and 4 and 5 in 2023), and 30 so-called small molecules, bringing the total to 34 new chemical entities (NCEs), including TIDES and small molecules ( Figure 1 ) [ 1 , 2 ]. In 2024, the proportion of biologics among NCEs was slightly higher than in previous years: 32% of all drug approvals have been for biologics, compared to 28% over the past six years. This increase reflects the growing importance of biologics in the pharmaceutical market. Indeed, out of a total of 304 drugs approved over these six years by the FDA, 87 are biologicals [ 2 ]. This year, the Center for Biologics Evaluation and Research (CBER) has given the go-ahead for 24 new Biologics License Applications, a number similar to the 22 approvals in 2023, which at that time marked a notable increase compared to the 12 and 13 registered in 2022 and 2021, respectively [ 3 , 4 ]. The Biologics License Applications authorized this year included several medical devices and computer software related to blood management and analysis and also diagnostic tests. As in previous years, this manuscript analyzes the 50 new drugs approved by the FDA in 2024 based solely on their chemical structure. The number of references has been minimized to ensure a smooth flow of the manuscript. Ref. [ 1 ] provides more information.
2. Discussion
This year, the FDA has approved 16 biologics ( Table 1 ), confirming the trend observed in recent years. In this regard, since 2015, the number of biologics approved each year has consistently been in the double digits, except in 2016, when only 7 were authorized (7). Of the biologics given the green light in 2024, 13 are monoclonal antibodies (mAbs), surpassing the 12 approved last year and setting a new record for this class of drugs. The remaining approvals have been given to three proteins. Once again, mAbs are the most approved drug class, not only among biologics but across all drugs, accounting for 25% of all medications authorized. Although cancer continues to be the principal target for mAbs (50% of the total), the number of medical indications is widening through the incorporation of Alzheimer’s disease and skin and blood conditions, among others. Two of the mAbs to receive the green light this year, concizumab-mtci (Alhemo TM ) and marstacimab-hncq (Hympavzi TM ), are indicated for the same target, namely the prevention or reduction of bleeding episodes related to hemophilia A or B. Four of the mAbs are indicated for the treatment of skin-related disorders: lebrikizumab-lbkz (Ebglyss TM ) for eczema; nemolizumab-ilto (Nemluvio TM ) for hard, raised bumps; and cosibelimab-ipdl (Unloxcyt TM ) for cutaneous squamous cell carcinoma. If proteins are considered, a fourth biologic, letibotulinumtoxinA-wlbg (Letybo TM ), has also been approved for the same target. Therefore, a quarter of the mAbs authorized this year are indicated for the treatment of the skin. This year, a third mAb, namely donanemab-azbt (Kisunla TM ), has been given the green light for the treatment of Alzheimer’s disease, and it was preceded by approvals for aducanumab-avwa (Aduhelm TM ) in 2021 and lecanemab (Leqembi TM ) in 2023. The approval of aducanumab-avwa raised serious discussion regarding its effectiveness. While the latter two were developed by Biogen, Eli Lilly is behind donanemab-azbt. This drug is specially indicated for the treatment of individuals with early symptomatic Alzheimer’s disease, including mild cognitive impairment or mild dementia. As of 2023, no antibody-drug conjugates (ADCs) have been approved this year. Thus, 14 ADCs have been authorized to date, the last one in 2022. This year, three protein-based drugs have been given the green light by the FDA. Interestingly, Anktiva TM is a fixed-dose combination of an interleukin-15 receptor agonist with Bacillus Calmette-Guérin for the treatment of bladder cancer. The first is a fusion protein that contains a human IL-15 variant (nogapendekin alfa) attached to a dimeric human IL-15Rα sushi domain/human IgG1 Fc (inbakicept). Despite being one of nature’s most dangerous toxins, botulinum toxin has proven to be a rich source of new drugs, predominantly targeting facial wrinkles and glabellar lines, being referred to as “Botulinum toxin: bioweapon & magic drug” [ 5 ]. In this context, this year letibotulinumtoxinA-wlbg (Letybo TM ) has joined onabotulinumtoxinA (Botox TM ), abobotulinumtoxinA (Dysport TM /Azzalure TM ), rimabotulinumtoxinB (Myobloc TM ), incobotulinumtoxinA (Xeomin TM /Bocouture TM ), and prabotulinumtoxinA (Jeuveau TM ), which were already on the market. Finally, among the proteins, sotatercept-csrk (Winrevair TM ) has been approved for the treatment of pulmonary arterial hypertension. This drug contains the extracellular domain of the activin type 2 receptor, expressed as a recombinant fusion protein with an immunoglobulin Fc domain. Oligonucleotides and peptides, collectively known as TIDES, are classified as chemical entities, meaning that regulatory agencies require their approval based on criteria similar to those for small molecules. However, it should be noted that, in many cases, the structural complexity of TIDES is more similar to that of biologics than to that of small molecules. Although TIDES are typically more active than small molecules, they require smaller doses of the Active Pharmaceutical Ingredient (API). However, in some cases, such as peptides designed for diabetes and obesity, which have more than 30 residues and a large market potential, their production poses significant challenges in both upstream and downstream processes. TIDES have transcended the scientific field and gained significant visibility in society, with a notable presence in the mass media. While five peptides and four oligonucleotides were released into the market in 2023, two peptides and one oligonucleotide have been approved by the FDA this year. The two peptides, palopegteriparatide (Yorvipath TM ) and pegulicianine (Lumisight TM ) contain a large polydisperse PEG moiety as indicated in the name of the API. The authorization of these medications reflects the resurgence of pegylated drugs after the withdrawal of peginesatide (Omontys TM ), a hyperpegylated disulfide cyclic peptide dimer, from the market in 2013. In this context, 2021 saw the approval of
3. Conclusions and Perspectives
In recent years, we have started this section of our annual article referring to COVID. As we anticipated last year, COVID is no longer ranked as a global concern in 2024, as it is now understood by society and the medical profession as a “new flu”. It is likely that people will receive a COVID vaccination annually, alongside the flu vaccine. However, we must consider the emergence of another disease related to COVID, namely long COVID. In most cases, it is a chronic condition, with symptoms that appear and disappear cyclically. It can be mild or severe, and, in some cases, it can lead to disability. The number of new cases of long-term COVID is decreasing, as it is directly related to the presence of COVID, which is receding. Long COVID must be treated as a new disease, and targeted treatments must be developed and investigated. This year, no drug from the so-called GLP-1 class has been approved, but this class of drugs remains one of the pharmaceutical industry’s driving forces. In this regard, the approval of retratutide is eagerly anticipated, followed by that of cagrilintide, mazdutide, pemvidutide, and survodutide (in alphabetical order), with more to come. Likewise, semaglutide (GLP-1 agonist) and tirzepatide [double agonist (GLP-1 and GIP) have been authorized for indications other than diabetes and obesity. In this regard, semaglutide has been authorized for reducing the risk of cardiovascular disease in individuals presenting a certain degree of obesity, while tirzepatide has very recently received the green light for the treatment of severe obstructive sleep apnea. This is an indication that a priori is very far from the original one. Finally, both drugs are being studied for other indications, including anxiety, alcoholism disorder, depression, and kidney disease. The introduction of these drugs for the treatment of mental and even neurodegenerative illnesses will elevate their status from “blockbusters” to “panaceas”. In terms of sustainability, the chemical-pharmaceutical industry faces a significant dilemma. On the one hand, there is a pressing need to eliminate the use and production of per- and polyfluoroalkyl substances (PFAS) due to their harmful effects on human health. The C-F bond is extremely strong in organic chemistry, making it highly resistant to degradation, which results in the contamination of soil and water (ground and surface). It is anticipated that the use of trifluoroacetic acid (TFA) will be restricted in Europe [ 8 ]. On the other hand, nearly 40% of chemically synthesized drugs contain F, and their production relies on PFAS. It is clear that these drugs are highly beneficial for public health and that F is irreplaceable—substituting it with H in the same compound would nullify its biological activity. However, the production of these drugs necessitates the use of environmentally harmful substances. Three antibiotics have been approved this year; two are fixed-dose combination drugs ( Figure 16 ), but all of them have structures (cephalosporin and penem derivatives) that have been known for more than twenty years, thereby indicating the difficulties encountered in bringing de novo antibiotics into the market. 2024 has been an excellent year in terms of the number of new drugs approved (50), consistent with the figures in recent years [55 (2023), 37 (2022), 50 (2021), 53 (2020), 48 (2019), and 59 (2018)], thereby confirming the robustness of the pharmaceutical industry. This year, 16 biologics have been authorized, matching the average of the last six years, which totaled 86 approvals. With 13 approvals this year—one more than each of the previous two years—mAbs have consolidated their status as the most significant class of drugs. Although cancer continues to be the most important indication for mAbs, this year three have been authorized for skin targets. Furthermore, the third mAb for Alzheimer’s disease, namely donanemab-azbt, has received the green light, following lecanemab in 2023 and aducanumab-avwa in 2021. TIDES—two oligonucleotides and two peptides—have joined the ranks of this class of drugs. While there have been fewer authorizations than last year (9), peptides and oligonucleotides still represent almost 10% of all drugs approved. TIDES and biologics together account for 40% of all drugs approved this year (20 over 50), reaffirming the slight decrease in the so-called small molecules in the pharmaceutical market, which predominated just a few years ago. The two peptides approved this year, palopegteriparatide (Yorvipath TM ) and pegulicianine (Lumisight TM ), contain large polydisperse PEG. In comparison, three pegylated drugs received the green light in 2023: two TIDES—the peptide zilucoplan (Zilbrysq TM ) and the oligonucleotide avacincaptad pegol (Izervay TM )—and the enzyme pegunigalsidase alfa (Elfabrio TM ). This trend reaffirms the resurgence of PEG as a component of drugs, despite the issues associated with peginesatide (Hematide TM , Omontys TM ), wh
| DOI | 10.3390/molecules30030482 |
| PubMed ID | 39942587 |
| PMC ID | PMC11820978 |
| Journal | Molecules |
| Year | 2025 |
| Authors | Beatriz G. de la Torre, Fernando Alberício |
| License | Open Access — see publisher for license terms |
| Citations | 26 |