NEW YORK – The US Food and Drug Administration in 2024 approved dozens of new and expanded precision medicine indications. Although most of these approvals were still in cancer and rare conditions, the field of precision medicine is poised to enter bigger markets for Alzheimer's, heart, and autoimmune diseases that could better patients' lives — if they can afford and access them.
"It's been a year with a lot of novel drugs, biomarkers, and approaches coming to market," said Susanne Munksted, chief precision medicine officer at health technology firm Diaceutics. "Precision medicine mainly started in oncology, but for the last couple of years, it's been expanding into other areas. We're almost at a tipping point where [precision medicine] is going from being niche to becoming more mainstream."
By Precision Medicine Online's count, the FDA approved 48 precision medicine indications last year: 35 biomarker-indicated drugs, eight autologous cell therapies, and five gene therapies (see chart at the end of the story). There were approximately 70 percent more precision medicine approvals in 2024 compared to 2023, when there were 28 such approvals.
There were numerous firsts. Iovance and Adaptimmune brought the first two autologous cell therapies to market for solid tumors (read more on cell therapy advances in 2024 here). Merus was the first to gain FDA approval of a treatment for NRG1 fusion-positive tumors. For the first time, there are gene therapies for patients with rare diseases like metachromatic leukodystrophy and aromatic L-amino acid decarboxylase deficiency (read more on gene therapy advances in 2024 here).
There are now drugs targeting novel biomarkers, like claudin 18.2 expression in gastric cancer and KMT2A translocations in acute leukemia. The FDA extended the list of cancer treatments that can be given in a tissue-agnostic fashion based on the presence of a biomarker, including HER2 overexpression and NTRK fusions, and made Eli Lilly's Retevmo (selpercatinib) accessible to patients as young as 2 years old if they have solid tumors with RET fusions.
Another beta-amyloid targeting drug for Alzheimer's patients came to market in Lilly's Kisunla (donanemab), and leukemia patients got a new CAR T-cell therapy in Autolus' Aucatzyl (obecabtagene autoleucel).
Drugmakers continued their assault against targets previously considered undruggable like KRAS or difficult to inhibit like PI3K. "What's exciting is we're moving from 'easier targets' … to things like PIK3CA and KRAS, which are not easy to hit with drugs," said Mark Burkard, director of the University of Iowa's Holden Comprehensive Cancer Center. As a breast cancer specialist, Burkard is particularly encouraged that next-generation PI3Kα inhibitors like Roche's Itovebi (inavolisib) have a lower rate of serious hyperglycemia, an adverse event that limited use of Novartis' Piqray (alpelisib) in patients with PIK3CA-mutated tumors.
Although around 80 percent of the 48 precision medicine approvals were in oncology, the pace of approvals in other disease areas will likely accelerate in coming years. Industry observers predicted, for example, that the "persistent and steady drumbeat of cell and gene therapy approvals throughout 2024" will only get louder in coming years, particularly since the FDA has promised regulatory flexibility to ease the path to market for rare disease treatments.
But there are also signs that precision medicines aren't going to be relegated to orphan indications. A beta-amyloid-targeting Alzheimer's drug like Kisunla is expected to reach $3 billion to $5 billion in peak annual sales by some estimates. In the cardiovascular disease space, drugmakers are racing to advance treatments that lower lipoprotein(a), a biomarker associated with increased risk of heart disease that is elevated in more than 1 billion people globally. More than 15 million people in the US were diagnosed with an autoimmune disease from 2011 to 2022, and autologous CAR T-cell therapies are starting to show promise in conditions like lupus.
Unlike in hematologic malignancies, where the goal of CAR T-cell therapy is to direct the immune system to kill cancer cells, in autoimmune diseases the aim is to reset the immune system, observed Howard McLeod, director of the Center for Precision Medicine and Functional Genomics at Utah Tech University, adding that some of the emerging data "look amazing." In a German study published in 2024, for example, all 15 patients with refractory autoimmune diseases who received a CD19 CAR T-cell therapy achieved drug-free remission at a median follow-up of 15 months. In data like this, McLeod sees precision medicine's "potential to help the masses."
More precision medicines … wider access gaps?
With the increasing availability of precision drugs, biomarkers, and diagnostic tests, McLeod also worries about exacerbating access disparities and the pressure on physicians to keep up with rapidly advancing science. Affordability is certainly a growing concern. Orchard Therapeutics' gene therapy Lenmeldy (atidarsagene autotemcel), approved in 2024 for metachromatic leukodystrophy, is now the most expensive drug in the world with a $4.25 million list price. And Adaptimmune's Tecelra (afamitresgene autoleucel) for synovial sarcoma became the costliest cell therapy last year priced at $727,000. The high upfront costs of precision medicines, particularly cell and gene therapies, have payors contemplating outcomes-based contracts and other payment models.
The budgetary pressures on healthcare systems stand to increase as precision medicines enter bigger disease markets. "If you think it's bad getting things paid for for a rare leukemia, well, now you have to try do it for something that's pretty common," McLeod said, reflecting on the unwanted consequences to the healthcare system should pricey CAR T-cell therapies become available for autoimmune conditions. "Even if [the treatment costs] only $100,000, that's still a lot of money. … All these issues we've talked about [with precision medicine] in cancer are now starting to come true in other areas."
McLeod recalled simpler times back in 2009 when the FDA updated the labels for EGFR monoclonal antibodies, limiting their use in colorectal cancer patients with KRAS mutations. "It was just KRAS. You didn't have to know any of the variants. You just had to know those four letters and that insurance wouldn't pay" unless you showed patients were KRAS wild type, said McLeod.
In 2024, the FDA approved drugs for cancers harboring KRAS G12C mutations, NRG1 fusions, three types of EGFR alterations, MAGE-A4 expression, four human leukocyte antigen genotypes, and more. Doctors have to choose from a crowded test landscape to gather biomarker information on their patients, keep up with constantly changing guidelines, and navigate a complex web of insurance policies. "All that is coming together and increasing the problem, and the disparities are growing," McLeod said, noting that too many people are still not being tested for biomarkers to gauge their eligibility for precision medicines, and even when they are, they still may not receive the right treatment.
Diaceutics has been tracking precision medicine access gaps and presented a real-world data analysis in 2024 showing that only 12 out of 800 patients, or 1.5 percent, with NTRK fusion-positive metastatic solid tumors ended up receiving a commercially available NTRK inhibitor in the second- or later-line setting. The other 788 patients with NTRK fusions in the analysis got another targeted drug, chemotherapy, immunotherapy, or a chemo/immunotherapy combination. "The NTRK inhibitor example is an especially sad one because those drugs are so active," said McLeod, who was involved in the research with Diaceutics. "There are very few situations where that wouldn't be the first [therapy] choice."
McLeod founded Clarified Precision Medicine, a company that provides molecular tumor board (MTB) support to help oncologists decipher patients' genomic test reports and make treatment decisions. If Clarified's growth in 2024 is any indication — the firm netted $1.2 million in seed funding, began working with xCures to bolster its human expertise with artificial intelligence-based data extraction and analysis, and inked partnerships with community cancer centers — the need for such support will only expand with the availability of more precision medicines.
Seeing the need among his colleagues, Burkard helped set up an MTB while at the University of Wisconsin's Carbone Cancer Center and is trying to do the same at Iowa, where he joined as cancer center director a few months ago. "I do worry that there are these rare variants of common diseases where the patients might not receive the best possible care just because the physician has never seen an NRG1 fusion," he said.
Practices all over the state send patients to the University of Iowa's cancer center. It used to be that community oncologists would refer patients with rare, hard-to-treat cancers that they might not be used to treating, but in the last five years, there's been a shift "now that every 'common histology' is a collection of rare histologies and rare genetics," Burkard said. "More of those patients are coming to us, and we're seeing the common cancers, too."
Biopharma deals, layoffs, reorganization
Despite new precision medicines coming to market in 2024, market analysts tracked fewer mergers and acquisitions in the biopharma space compared to past years and a fair amount of restructuring and layoffs. Vamil Divan, managing director at the investment firm Guggenheim Partners, attributed this to continued macroeconomic conditions, uncertainty around policies and regulations, the ups and downs of drug development, and higher interest rates making it challenging for smaller drugmakers to borrow the funds they need to advance their pipelines.
A slew of small and midsized pharma companies, like Exelixis, Black Diamond Therapeutics, and Erasca, had to make hard decisions last year about which products to advance with limited resources, including precision drugs. There were layoffs at Gilead after it reported relatively flat Q3 sales of its cell therapy products; at BioMarin following slow sales of its hemophilia A gene therapy Roctavian (valoctocogene roxaparvovec); and at Bluebird Bio, which is restructuring to focus on commercializing several gene therapies, including the sickle cell treatment Lyfgenia (lovotibeglogene autotemcel).
Divan expects M&As will eventually pick up since many big pharmaceutical companies are facing loss of patent protection for some of their best-selling products in coming years. "I don't know when that changes, but these large companies do need these new products … from the small companies to fill their pipelines," he said.
Merck's Keytruda (pembrolizumab), which is approved for several biomarker-defined and all-comer cancer indications, still comprised 45 percent of the firm's revenues in Q3 2024. With the 2028 patent expiry for the checkpoint inhibitor fast approaching, Merck talked up its portfolio diversification plans during every earnings call in 2024. Bristol Myers Squibb is singing the same tune with Opdivo's (nivolumab) patent expiring in 2028, and Pfizer is in the same boat with its hormone receptor-positive, HER2-negative breast cancer drug Ibrance (palbociclib) losing patent protection in 2027.
Big pharma is "struggling to replace those sales they're going to lose … and they're just trying to break even or offset [those losses] with pipeline advancements," said Divan, who expects limited growth outlooks in the pharma sector in the next five to seven years. The exceptions he sees are Novo Nordisk and Eli Lilly, which sell the wildly profitable GLP-1 agonists for weight management, Wegovy (semaglutide) and Zepbound (tirzepatide), and have become "their own little mini-sector" that is attracting lots of investment.
GLP-1 agonists are not biomarker-directed today, and drugmakers are presently focused on selling these drugs to the broadest possible market, but some researchers, biotechs, and even Novo Nordisk are dipping their toes into precision medicine strategies. "From a health economic perspective … I can see a future where these broader indications eventually will be diagnostic-guided or biomarker-guided," Diaceutics' Munksted said. "We are not there, but that's where we are headed."
On the M&A front, antibody-drug conjugates, which are often designed to target specific tumor biomarkers, were the focus of several deals, including Johnson & Johnson's purchase of Ambrx Biopharma for around $2 billion; a $1.03 billion licensing deal between Ipsen and Foreseen Biotechnology; and tie-up between Merck KGaA and Caris Life Sciences that could be worth as much as $1.4 billion to Caris. The success of ADCs on the market like AstraZeneca and Daiichi Sankyo's HER2-targeted Enhertu (trastuzumab deruxtecan) and others has established this drug class as an "almost routine therapy" in oncology, said Divan, who expects continued biopharma investment in this space.
Other notable precision oncology-focused deals included Novartis' acquisition of MorphoSys for $2.9 billion and Regeneron's purchase of 2seventy Bio in a more than $5 million deal. Radiopharmaceuticals, another boom area in precision oncology, continued to attract investment, with AstraZeneca buying Fusion Pharmaceuticals in a $2.4 billion deal and Novartis snatching up Ratio Therapeutics' SSTR2-targeted treatment capabilities for $745 million.
During the year, nearly all the big pharmas also invested heavily in artificial intelligence, hoping to reduce spending, discover drugs cost effectively, and run clinical trials efficiently. According to Daniel Brennan, senior equity research analyst and managing director at investment firm TD Cowen, investments in AI will only increase in 2025 and beyond. "AI will become more a part of … what companies have to think about in order to be successful … and increasingly a topic for investors to think about," Brennan said.
'A pretty good year' in diagnostics
Amid macroeconomic uncertainty, M&A activity remained sluggish in the in vitro diagnostics sector, as well. According to an analysis by Precision Medicine Online's sister publication 360Dx, there were only 20 full-company M&As announced or completed in 2024, far below the number of M&As that occurred during the COVID-19 pandemic years of 2020 or 2021, and none of the 2024 deals topped $1.0 billion. A few notable diagnostic deals in the precision medicine space included Laboratory Corporation of America's $239 million purchase of Invitae's tests, including its hereditary cancer assets, after Invitae filed for Chapter 11 bankruptcy, and Tempus AI's $600 million purchase of Ambry Genetics.
Still, Brennan felt it was "a pretty good year" in certain diagnostics sectors. Minimal residual disease testing, for example, "has seen tremendous growth with Natera the leader" with its Signatera MRD test, he noted. The $20 billion total addressable market for MRD monitoring in four solid tumors indications — colorectal, breast, lung, and bladder cancer — is "minimally penetrated," Brennan recently wrote in a note to investors, and there are many companies who are developing "ultrasensitive" MRD approaches. An FDA advisory committee unanimously supported use of MRD as an accelerated approval endpoint in multiple myeloma clinical trials, which Brennan predicted bodes well for Adaptive Biotechnologies' ClonoSeq MRD test, as it will drive further biopharma demand to use the test in drug trials.
Brennan also sees continued "enthusiasm" for comprehensive genomic profiling and companies like Guardant Health and Roche's Foundation Medicine. Tempus AI also went public this year, and Caris Life Sciences' MI Cancer Seek NGS test secured FDA approval, which the company touts as the first whole-exome and whole-transcriptome sequencing solid tumor profiling test with companion diagnostic indications to garner market authorization in the US.
There were some ups and downs in the blood-based cancer detection space. One upside Brennan highlighted was the FDA's approval of Guardant Health's Guardant Shield assay for detecting colorectal cancer for average-risk patients starting at age 45, making it eligible for national Medicare coverage. A downside he flagged was the performance of Freenome's PREEMPT CRC test, which disappointed investors.
These single-tumor screening tests are precursors to multi-cancer early detection (MCED) testing. McLeod, who previously oversaw a pilot program through which certain Intermountain Health employees can access Grail's MCED test Galleri, felt 2024 was "a neutral year" without any big data splashes, good or bad. Healthcare providers continued to question whether these tests can detect multiple cancers and detect them early enough to make a meaningful impact in patients' lives. "The data around when you should act could be as much as a decade away," McLeod predicted, adding that in the interim, there's more support for using these tests to screen for one type of cancer, like colorectal cancer. "There's a difficulty in quantitating the societal value of capturing multiple cancers," he acknowledged, but the conversation will mature, he believes, as more data emerges on MCED tests' ability to detect cancers early that otherwise would not be possible.
Stephen Gruber, chair of the Center for Precision Medicine at City of Hope, agreed the field needs more data on the performance of MCED tests before routinely using them across tumor types, but noted that doctors can start to better rely on blood-based screening tests as the FDA approves them for detecting specific cancers like it has with Guardant Shield and Exact Sciences' Cologuard in colorectal cancer.
City of Hope is eager to advance the science behind MCEDs and is conducting multiple clinical trials involving the technology but hasn't integrated them as part of standard care outside of the research setting. When patients come in with MCED test results, Gruber considers that information in their care, but he does not routinely order them and doesn't think currently available blood-based screening tests are ready for prime time use outside of FDA-approved settings. "No test is perfect," he acknowledged, but often with MCED, "a negative test is not perfectly reassuring, and a positive test can lead to a diagnostic odyssey that is often unfulfilling, and you don't quite know when to stop."
Outside of cancer, Brennan flagged the strong financial performance of GeneDx, a leader in genetic testing to diagnose rare diseases, with its stock price increasing from around $1 to $80 over 2024. In other areas, the availability of anti-amyloid Alzheimer's drugs and the prospect of Lp(a)-lowering treatments for cardiovascular disease are spurring diagnostics markets to support their use. Even though no Lp(a)-lowering drugs have yet reached the market, pharmaceuticals companies have already launched campaigns to educate cardiologists about the need to test for this biomarker, which isn't part of standard care.
The latest Alzheimer's drugs like Biogen and Eisai's Leqembi (lecanemab) and Eli Lilly's Kisunla require confirmation of beta-amyloid pathology in patients' brains and carry a boxed warning for the increased risk of amyloid-related imaging abnormalities, characterized by brain swelling and microhemorrhages, in those carrying two copies of the APOE4 variant. Since beta-amyloid is typically gauged through expensive PET scans and invasive cerebral spinal fluid testing, efforts picked up in 2024 to develop (see here and here) less-invasive and cost-effective blood tests for assessing amyloid pathology, while doctors performed more APOE tests to help weigh the risks and benefits of giving anti-amyloid drugs to patients.
Around 50 percent of Alzheimer's patients have one copy of APOE4, and 15 percent have two copies. There have been several reported deaths among APOE4 homozygous patients receiving anti-amyloid drugs. Sudha Seshadri, the founding director of the Glenn Biggs Institute for Alzheimer's & Neurodegenerative Diseases at the University of Texas Health Science Center at San Antonio, is encouraged to see that doctors are doing more APOE testing, and the field is collecting post-marketing data on adverse events. "It's a step in the right direction," Seshadri said, but she would like to see more data collection, especially since minority groups were not adequately represented in clinical trials of these drugs. "We need to be very careful because if there are devastating side effects, that will set back the trust of patients and their families and impair future trials of other agents."
Precision medicine in an uncertain 2025
With precision medicine's growth outside of oncology, Diaceutics' Munksted sees a need to come up with a broader definition of what it comprises. Within oncology, the term precision medicine is tightly tied with biomarkers and diagnostic testing, but this may not resonate in other areas involving cell and gene therapies or when discussing precision medicines for rare diseases. The biomarker tests that inform precise treatments for other conditions like heart disease and Alzheimer's may be quite different from the genomic profiling that has become established in precision oncology. Wearable devices that capture digital biomarkers like behavioral changes, tremors, or abnormal heart rates, for example, could further broaden the definition of precision treatment, Munksted reflected.
Definitions aside, the ideas advanced in precision oncology — using combination treatments to suppress multiple biological mechanisms and pathways and testing for multiple biomarkers of risk, progression, and response — are helpful in thinking about what is needed to individualize Alzheimer's care, in Seshadri's view. "APOE4 is just the tip of the iceberg," she said, noting the need to more deeply study the relationship of Alzheimer's progression markers like APOE, tau, and progranulin with treatment response, as well as the role of environmental factors like sleep and air pollution.
"We don't really know anything about the [environmental] interaction with the treatments that we are offering, so there's much to be learned," Seshadri said, underscoring the need for national registries and partnerships to collect this type of data. "Perhaps this will be learned with the second generation of drugs with a lower risk of ARIA."
The increasing use of AI in the healthcare sector will also broaden the definition of precision medicine. In 2024, not just drugmakers but also academic researchers, device companies, and stakeholders across the healthcare sector invested in AI for a variety of purposes (read more on 2024 AI trends in precision medicine here), including for detecting cancer, prescreening patients for genomic alterations, and predicting treatment response. AI-driven applications are already being deployed in digital pathology, and TD Cowen's Brennan sees "a lot of hope in AI" in that sector.
Going into 2025, Brennan doesn't see "a big catalyst for more deals" in the diagnostics sector compared to 2024. The space could pick up and the larger companies could become "more willing as buyers," he opined, if acquisition targets become more attractive by performing better financially. Factors like a "more conciliatory" Federal Trade Commission under President-elect Donald Trump and state biomarker bills passed in more than 20 US states could also positively impact M&A activity, he predicted.
The FDA's bid to regulate lab-developed tests continued to agitate the lab community in 2024 and is a looming uncertainty going into 2025. The FDA released a final rule outlining plans to regulate LDTs, which spurred lawsuits from the Association for Molecular Pathology and the American Clinical Laboratory Association. This fall, AMP told its members that the field is in "limbo" as it tries to defeat the final rule in court and also help members prepare for its implementation.
The Department of Health and Human Services under Trump back in 2020 had stated that the FDA can't require premarket review of LDTs without notice-and-comment rulemaking, but as legal experts noted at the time, the HHS didn't explicitly state the FDA lacked the statutory authority to regulate the space. Still, new administrations often bring different policy perspectives. After the presidential election in November, the College of American Pathologists asked Trump's transition team to recommend rescinding the final rule, and it formed a new group to push lawmakers to address LDT regulation through legislation, though past bills have been unsuccessful. "The uncertainty around is the FDA going to regulate [LDTs] or will they not be allowed to … may make [diagnostics] not a great space to place bets," McLeod said.
Vaccine makers' stock prices dropped this fall when Trump announced Robert F. Kennedy Jr., who has touted false claims about vaccine safety, as his pick for HHS secretary. Pharmaceutical companies are "definitely anxious" about what the new year will bring, Divan said, but noted that at a recent meeting between big pharma executives, Kennedy, and Trump, they reportedly found common ground on the need to bring down drug costs through pharmacy-benefit management (PBM) reform.
While he expects legislators will confirm Trump's picks to lead HHS and its agencies, Divan doubts they will change policies and operations at health and research agencies dramatically or pull already approved vaccines and drugs from the market. "A lot of this is just panic and concern about the new administration," said Divan. Although he can see Kennedy's comments around vaccine safety affecting their uptake and possibly creating higher hurdles to market for innovative medicines like gene therapies, he believes that "if the data are convincing enough, they'll still make it through."
Despite the uncertainties ahead, Gruber is also optimistic about City of Hope's ability to deliver precision medicine and make a difference for patients and providers. He expects adoption of germline genetic testing to assess the risk of inherited cancers to continue and advancements in vaccines that can prevent these tumors from forming. He sees forthcoming technical improvements to CAR T-cell engineering and "continued strides" in solid tumors. There will be more drugs "approved for rare disease with well-characterized mechanisms of action and specific mutations," he predicted. The demand for genomic profiling will only increase, he believes, and AI will enable precision medicine delivery at scale.
"The future of precision medicine is bright, and transient changes in the broader landscape do not diminish my enthusiasm," Gruber said.