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With its “Antibodies to Watch” publication, The Antibody Society provides a comprehensive annual survey of the current antibody-based therapeutic landscape, with detailed summaries in key development areas: Approved antibody drugs from the previous year; the latest promising drug candidates currently under regulatory review; and a wealth of supplemental data sets for antibodies undergoing late-stage (Phase 2, Phase 2/3, or Phase 3) therapeutic development around the world. This pointed and thoughtful analysis makes “Antibodies to Watch” required reading for anyone hoping to stay current with the commercial antibody therapeutic landscape.
Personally, I like to use “Antibodies to Watch” as a test of how Antibody Solutions is keeping up with the rest of the industry. Essentially, the question I ask is this: Are the services we offer at our contract research organization still in line with the demands of the current market and, more importantly, are they in line with discovery methods that are most likely to succeed? (Spoiler alert: The answer to both of these questions is “yes,” but I’ll explain how we get there.) Much like last year, I also thought it would be valuable to see how approvals developed in 2024 in relation to The Antibody Society’s original predictions.
Antibody Drugs Approved in 2023
The Antibody Society’s 2024 report covers sixteen drugs that were approved for commercial release by a governing body in the United States, Canada, Europe, and Asia. Of this list, ten achieved first approval in 2023 from the Food and Drug Administration (FDA), the European Medicines Agency (EMA), or another governing body in North America or the European Union (EU). Due to the limited information available for drugs from the remaining territories (namely Russia and China), we’ve concentrated our analysis on the ten drugs that achieved approval in either North America or the European Union: Leqembi™ (lecanemab-irmb), Rystiggo® (rozanolixizumab-noli), Veopoz™ (pozelimab-bbfg), Omvoh™ (mirikizumab-mrkz), Talvey™ (talquetamab-tgvs), Elrexfio™ (elranatamab-bcmm), Epkinly™ (epcoritamab-bysp), Columvi® (glofitamab-gxbm), Zynyz™ (retifanlimab-dlwr), Alhemo™ (concizumab), and Ebglyss® (lebrikizumab-ldrm).
Over the course of 2023, The Antibody Society’s website published updates for existing drugs for which new indications were being approved. These updated indications were left out of the “Antibodies to Watch” analysis, as they are examples of expanded indications rather than entirely new molecules being approved for the first time. We elected to include them in our own analysis, though, since we feel they provide helpful insight into how antibody-based therapeutic development is growing. These drugs are Bimzelx® (bimekizumab-bkzx) and Loqtorzi™ (toripalimab-tpzi).
Figure 1: Therapeutic Antibodies in Drugs First Approved in Europe or North America in 2023
Novel antibody therapies approved by the United States Food and Drug Administration in 2023. They are presented here with their applications (indicated by color) and their modalities (indicated by checkmark). Eleven out of thirteen are first-ever approvals; bold-outlined therapeutics Loqtorzi and Bimzelx are pre-existing drugs with new indications that were approved in 2024. Information is taken from Crescioli et al and Strohl. (Please Note: Information given in this and subsequent figures is based on our own best research and cross-referencing. We welcome you to contact us regarding any corrections or omissions.)
As seen in Figure 1, 2023’s class of approved antibody-based therapeutics are split nearly evenly between six cancer indications and seven non-cancer indications. Most of the non-cancer-indicated drugs are designated by The Antibody Society as for ''immune-mediated disorders'' (psoriasis, dermatitis, etc.), with one for hemophilia (designated as “cardiovascular disease”) and one for Alzheimer’s disease (“neurological disease”). All thirteen are full-length antibodies (Columvi’s sequence is Fab-Fc x Fab-Fab-Fc). As with last year, kappa light chains are predominant, with only three drugs (Talvey, Epkenly and perennial outlier Columvi) featuring kappa/lamda. “All four bispecifics,” notes the report, “target combinations of antigens that are unique among the currently approved antibody therapeutics”; in our view, that makes them particularly exciting as new drugs.
There are notable similarities and differences between this past year’s approved antibody drugs and those approved in 2022. For both years, a similar number of brand new drugs were approved – eleven in 2023 compared with twelve in 2022. Each year featured a crop of drugs that were more-or-less equally divided between cancer and non-cancer indications. Also in both years, four approved drugs were bispecifics and one was chimeric. At the same time, 2023’s class of therapeutics featured a less diverse set of attributes compared to those from the year before. There were, for instance, no antibody drug conjugates (ADCs) approved in 2023. Further, all four bispecifics this year were for cancer drugs, whereas in 2023 there were three in cancer and one indicated for Alzheimer's disease.
Antibodies Undergoing First Regulatory Review, Reviewed
In our previous review of “Antibodies to Watch,” we went directly from exploring the attributes of 2022’s approved antibody therapeutics to an overview of common development trends. The Antibody Society, however, usually devotes a significant amount of space to a select number of drug candidates that – as of the time of publication – were “undergoing review by at least one regulatory agency.” We’ve dug into data for nine antibodies that The Antibody Society highlights, all of which are under evaluation by either North American or EU regulatory bodies. Figure 2 displays the International Nonproprietary Names (INNs) and attributes of these therapeutic antibodies.
Figure 2: Therapeutic Antibodies Undergoing First Regulatory Review in North America and the European Union
Antibodies that were, as of January, 2024, undergoing First Regulatory Review by the FDA, EMA or other regulatory body in North America or the European Union. They are presented here with their applications, indicated by color, and their modalities, indicated by checkmark.
This round of prospective therapeutic antibodies differs quite starkly from the year’s approved drugs. This time, we see that cancer-targeted drugs are a distinct minority; the non-cancer drugs cover a less diverse range of targets, all of them classified by The Antibody Society as “cardiovascular disease or hemostasis” targets. Perhaps most notable, however, is the source connected with each antibody therapy: Of the proposed therapeutics, only two out of nine are distinctly identified by The Antibody Society as “humanized.” The report identifies most of them as “human” in origin, so it’s a bit of a toss-up as to which, if any, were discovered via live patient samples, human libraries, or human-transgenic rodent sources. (Despite our best efforts, we could find very limited information on the sources for most of these therapeutics.)
Antibodies in Phase 2 and Phase 3 Development
“Antibodies to Watch in 2024” provides an up-to-date, highly detailed list of therapeutic antibodies currently in development at major institutions throughout the world. At the time of publication, the list totaled 138 antibodies, with 70 targeted to cancer and 68 indicated for non-cancer targets. Just like last year, this expansive dataset portrayed a striking variety of antibody options being explored for therapeutic use. This was especially true of the cancer drug candidates, with 17 prospective ADCs and two reduced intensity conditioning (RIC) drugs (neither of which occurred in any of the listed non-cancer therapeutics). Some recurring themes were also present: Across both groups, unconjugated antibody formats dominated, as did kappa light chains.
Figure 3: Therapeutic Antibodies in Phase 2 and/or Phase 3 Development as of February, 2024
Antibodies that, as of February, 2024, were undergoing Phase 2, Phase 3 or Phase 2/3 development by major organizations. They are presented here with their applications, indicated by color, and their modalities, indicated by checkmark.
Also illuminating were the listed sequence sources for these candidates. Across both cancer and non-cancer targets, 80 of the proposed therapeutics are known to be derived from humanized sources. By comparison, 46 prospective therapeutics were derived from an unspecified “human” source (in addition, four were listed as chimeric in origin and two were murine). As with the antibodies under regulatory review, it’s hard to know which “human” antibodies were sourced from human-transgenic cells, naive human libraries, or some other source (like a human patient). While it would be great to have more details regarding these modalities, the utility and durability of humanized antibodies is as clear as ever. When viewed in light of data from the last 40 years of antibody therapeutic development, we see that this continues the trend of in vivo antibody discovery being the most reliable source for successful antibody-based therapeutics.
Approvals of Antibody Drugs in 2024 So Far
In the first seven months of 2024, only two entirely new antibody drugs were approved by the FDA. Not many details are available regarding the first therapeutic, Imdelltra™ (tarlatamab-dlle), which targets extensive-stage small cell lung cancer (ES-SCLC). It’s a bispecific cancer drug of unspecified (humanized, transgenic, human library, etc) origin, and it features a single-chain variable fragment (scFv-scFv-scFc) format. Kisunla™ (donanemab-azbt), the second debut antibody-based therapeutic to receive approval in 2024, is a full-length, humanized monospecific targeted to Alzheimer’s disease. The EMA, meanwhile, has been even more conservative with its approvals, with no brand new drugs receiving approval between the first of this year and the end of June.
This extremely limited number of antibody drug approvals in 2024 is reflective of a notably slow year for drug approvals in general, and especially underwhelming when compared with last year and the year before. Five antibody therapeutics had been approved by July 1st, 2023, and five FDA approvals (plus one emergency use authorization) were announced between January 1 and April 1, 2022. We might see a major shift towards the end of summer and the beginning of fall that reflects last year, when three new antibody drugs were approved in August, followed by an additional three in October. It’s possible, but let’s not hold our breath.
While there was some noticeable variation in the attributes of the two groups, the FDA-approved antibody drugs of 2023 don’t represent a radical departure from the previous year. Perhaps of significantly more interest to this analysis, however, are the number of existing drugs received approvals for new indications. Cancer-targeting Tevimbra® (tislelizumab-jsgr), a humanized monospecific, was one such FDA approval; the drug in question originally debuted in China in 2019. The EMA granted a marketing authorization application (MAA) awarded to Tivdak® (tisotumab vedotin), an ADC that was approved by the FDA in 2021. Developments such as this are a helpful reminder that, while new drug approvals are worth celebrating, targets for existing drugs can often be expanded in new and equally valuable ways.
Looking Ahead
So, what are the major takeaways from “Antibodies to Watch in 2024,” and what might we be able to look forward to in the months to come?
For starters, the enduring value of animal models in therapeutic antibody discovery was made clear once again in 2023. All thirteen of the drugs that received FDA or EMA approval were derived from antibodies developed through in vivo research. Most striking is the overwhelming (more than 90%) representation of humanized antibody sequences represented in 2023’s approved drugs. By contrast, we found that 75% of approved therapeutics (9 out of 12) were developed from humanized antibodies in 2022. The only drug that did not fit into that category, Veopoz, was derived from an antibody using a transgenic animal. To further complicate matters, it’s possible that we’ll see more drugs come to market that do not have a humanized antibody source (see Figure 2); it’s not yet clear if this represents an influx of human library or human patient donor antibody sources, or if a backlog of such antibody drugs is piling up while humanized antibodies make are arriving more swiftly to market. Either way, I find that my assertion from last year – that “animal-based technology … is still an essential component in the pursuit of novel antibody therapies” – is as true as it ever was.
Approvals for new antibody drugs so far this year seem to be a bit underwhelming, especially when compared to the outputs of 2022 and 2023. It’s likely that we’re in the kind of developmental slump that is inevitable downstream from the disruptions caused by the pandemic in 2020 and 2021, along with a period of market volatility over the two previous years. It’s also important to remember that last year was something of a late bloomer for antibody drug approvals: Despite its slow start, 2023 ended up being a strong year for antibody drugs and a record-breaking year for FDA approvals in general. While it’s not necessarily realistic to expect a repeat of that trend in 2024, it’s reasonable to expect things to pick up in the third and fourth quarters of the year as more drug discovery teams push for approvals.
The outlook is much more promising when we expand our purview from debut therapeutics to established drugs with newly expanded indications. For example, we have seen, and are likely to continue to see, more instances of biosimilars or other approved biologics having their approved indications or markets expanded. In one such case, osteoporosis medications Wyost® and Jubbonti® received contemporaneous approval; both are biosimilars to denosumab, which was already on the market under the brand names Xgeva® and Prolia®. In another case, the esophageal squamous cell carcinoma (ESCC) drug Tevimbra (tislelizumab) achieved approval this year in the US and Europe after achieving initial approval in China in 2019. Looking at the spotlighted drugs undergoing first regulatory review and at the remaining drugs that are currently in Phase 2 or Phase 3, however, we are greeted with an even more varied landscape of drug candidates.
The drugs currently in first regulatory review, as opposed to previous years, target a smaller range of diseases, and have mainly human sources (as opposed to humanized). This makes one wonder: Will we continue to see mostly human drugs in the pipeline? Or, with the improvement of machine learning and large language models, which have reduced many of the hurdles associated with humanization, will we see a return to humanized antibody drugs? That’s one major question we’ll be seeking to answer when we look at “Antibodies to Watch in 2025.”
There is plenty of exciting stuff in the pipeline, but we probably just won’t see it hit the market before the end of the year. I think we can also look forward to what Jules Adam of Labiotech calls a strategic year within the industry, one that sees increased collaboration between institutions of different sizes and capabilities, as well as bold new exploration into news discovery options. We’ll keep an eye on industry developments and expect to have more to contribute to the discussion when The Antibody Society publishes “Antibodies to Watch in 2025.” Until then, our virtual and real doors are always open. Let us know if you’d like to discuss the trends you’re seeing from your vantage point, and to learn together how our antibody discovery insights and capabilities can help advance your next initiative.
