The year 2023 was a challenging year for the life sciences industry, marked by a chilly biotech financing environment, uncertainty over legislative and policy changes, and an unpredictable macroeconomic outlook. Yet we also saw advances in cell and gene therapies, the launch of new effective drugs to treat patients with obesity, and mounting excitement about the promises of AI in drug discovery and clinical development. Looking ahead to 2024, leaders in the life sciences sector will be searching for indicators of progress: signs of advancement across the eco-system that suggest an improved and sustainable environment where scientific advances can be translated to patient benefits more rapidly and effectively. Here are some suggestions of what to look for as indicators of progress for life sciences in 2024.

Here is an overview of 7 potential key indicators of progress in the life sciences landscape to monitor in 2024:

1. Biotech financing – Will the XBI Biotech Index recover at least 20% in 2024?
   
   In 2023, we saw the sustained slump in investment flows and financial market returns since the heights of 2020/2021 for the life sciences sector, which have been in stark contrast to the scientific breakthroughs and promises that have emerged from start-ups and more mature firms alike. While the broader S&P500 index increased almost 25% in 2023, the SP& Biotech Index XBI rose less than 10% and the broader S&P Pharmaceuticals Select Industry Index gaimed only 2%. All types of biotech financing – venture capital investment, debt financing, and IPOs – are significantly down from their 2020/2021 levels, and this has placed significant stress on start-ups in need of financing or looking for exit strategies via the public markets.
   
   As we look ahead to 2024 – and humbled by the many mis-forecasts about how 2023 would play out – the big question for 2024 is whether the XBI biotech index will recover, as this will best reflect the support for the critical discovery and early-stage development of the next wave of innovative therapies, cures, vaccines, and other contributors to individual patient outcomes and population health. There are positive signals for a continuation of the recovery that began in late October 2023 due to a number of factors, including the expected drop in overall interest rates, a possible soft landing of the general economy, and more promising tech-biopharma collaborations and increased M&A activity.
   
   Look for the XBI Biotech Index to increase by 20% in 2024 as an indicator that investor sentiment and support for innovative life sciences has recovered. This would bring the index to its highest level since December 2021, although still 35% less than the peak level seen in February of that year. It would suggest the 2022/2023 slump for biotech is behind us and that this critical part of the life sciences eco-system has recovered.



2. M&A activity – Will the uptick in M&A activity continue and be sustained through 2024 at a 30% higher level?
   
   M&A wasn’t the lifeline in 2023 that many expected, but with a strong rally toward the end of the year, total activity level for the year was about 30% above the 2022 level. Acquisitions by larger companies of smaller biotechs, and mergers of biotechs, are a mainstay of the life sciences ecosystem and critical to maintaining productive portfolios of innovative medicines, accelerating clinical development, and bringing new treatments to patients.
   
   However, the pressure from rising interest rates, increasing inflation, concerns about a potential recession, and increased scrutiny by the Federal Trade Commission (FTC) put a damper on M&A and deal-making during much of 2023. And that was in spite of lower valuations for many smaller companies, healthy financing capacity in larger companies, and a need for replenishment of pipelines to offset the impact of impending patent losses. Amgen was able to claim victory when the FTC allowed Amgen to move forward with its $27.8 billion acquisition of Horizon Therapeutics under a settlement agreement. Some analysts believe the FTC’s decision suggests that reviews of other pending pharmaceutical deals could potentially pan out favorably for the companies involved, despite the final resolution and unwinding of the Illumina/Grail merger.¹
   
   The important success indicator for 2024 is whether the recent rising trend in M&A activity can continue throughout 2024 and result in a further 30% in M&A activity, bringing total value to about $200 billion?


3. Use of novel gene therapies – Will more than 2% of all U.S. patients with sickle cell disease get access to treatment with new approved cell-based gene therapies?
   
   A bright spot for the life sciences sector is the continued evolution of cell and gene therapies. CRISPR-Cas-9 editing has been shown to be promising for the treatment of sickle cell disease, according to recent studies. On December 8, 2023, the U.S. Food and Drug Administration (FDA) approved two milestone treatments, Casgevy and Lyfgenia, the first cell-based gene therapies for the treatment of sickle cell disease in patients 12 years and older.²
   
   However, treatment of sickle cell disease with gene therapy is highly complex and very costly. While the therapy may be effective in clinical trials, delivering that promise to patients in real-world settings may face significant challenges. Sickle cell disease predominantly affects a vulnerable, underserved population with limited and fragile access to sustained, quality healthcare. There are about 100,000 people in the USA affected by sickle cell disease,³  and there are special racial and ethnic challenges when addressing the disease, its complications, and related comorbidities.⁴  In addition, the infrastructure required to deliver this therapy is extremely specialized and currently available at very few centers, typically bone marrow treatment facilities with sickle cell expertise.
   
   Access to cell and gene therapy is a critically important challenge. Many patients with sickle cell disease are minority children of families that are covered by Medicaid, but a recent analysis by the Alliance for Regenerative Medicine found several barriers to access at the state level for cell and gene therapies for patients and providers given the lack of state resources and policies in this growing field of medicine. States often do not have a formal Medicaid coverage policy for cell and gene therapy products upon availability in the state, delaying patient access while the manufacturer and the state adjudicate coverage.⁵ Furthermore, many sickle cell patients are so advanced in their disease that gene therapy is not clinically warranted.
   
   FDA approval of the first cell-based gene therapies for sickle cell disease represents a great breakthrough for patients with this rare disease. As the first approved medicine in the U.S. to use CRISPR gene-editing technology, this approval may also hold exciting promises for other diseases. For the life sciences sector, these new treatments provide a test case for the speed with which revolutionary treatments reach the patients who will benefit from them. In this context, tracking the number of patients within the sickle cell population who will get access to the CRISPR-technology and achieve the benefits of the therapy within the first year will be a marker of progress.
   
   For the life sciences sector, a progress marker in 2024 will be seeing more than 2%, i.e., about 2,000, of the patient population with sickle cell disease in the U.S. being treated and benefiting from cell-based gene therapy.


4. Reimbursement of transformative drugs – Will broader reimbursement of new breakthrough drugs for the treatment of obesity bring increased patient access?
   
   2023 witnessed the dramatic rise in the novel diabetes drugs GIP and GLP-1 receptor agonists for weight loss therapy.⁶  The approval and launch of novel medications for the treatment of obesity is an inflection point for rethinking the prevention and treatment of obesity as a complex, heterogenous, chronic multidisease associated with other serious health conditions. The field is extremely competitive, with more than 143 new molecules in active clinical development and more than eight global pharmaceutical companies working on their own versions of GLP-1’s and GIP receptors, including oral formulations that will replace the injectable route of administration.⁷  At least six large clinical trials on obesity drugs are expected to have results reported over the next 12 months.⁸
   
   Payers and employers are concerned about the potential for increased costs due to the demand for these novel obesity treatments. Employers in the U.S. expect the biggest jump in healthcare costs in a decade, according to healthcare benefits consultants Mercer, Aon and Willis Towers Watson who are seeing employer healthcare costs jumping between 5.4% and 8.5% in 2024.⁹  While the rise in costs is explained by several factors, employers and their benefits consultants point to the soaring demand for costly obesity treatment drugs and wider availability of high-priced gene therapies. Of the projected 8.5% increase in employer healthcare costs in 2024, Aon anticipates that 1% increase in costs is coming from drugs for obesity treatment alone.
   
   Some payers, including Medicare, don’t reimburse drugs for treatment of weight loss; however, the growing body of evidence about outcomes benefits from the use of GLP-1’s for the treatment of obesity will potentially lead to a revision of the law that prohibits Medicare from reimbursing weight loss drugs. In a recent study published in the New England Journal of Medicine, a leading GLP-1 drug, semaglutide (Wegovy), was found to cut the rate of heart attacks by 28% among patients who were already taking statins and other medications to prevent heart problems. The drug also reduced the rate of cardiovascular-related deaths by 15% and strokes by 7%.¹⁰
   
   A revision of the law that prohibits Medicare from paying for weight loss therapies will be an important indicator of progress for the life sciences sector in 2024 as it will open access to obesity care for many seniors and will influence employer-based plans to provide coverage, based on growing amounts of clinical trial and real-world clinical evidence.


5. AI adoption in life sciences innovation – Will at least 30 drug candidates with AI-platforms advance in clinical development?
   
   The explosive focus on AI also impacted the healthcare eco-system with renewed predictions that AI will revolutionize healthcare delivery and life sciences R&D.
   
   AI will unquestionably have an important and growing role in life sciences R&D, product innovation, and commercialization, but the hard evidence of a positive impact at scale on life sciences is still in its infancy. Simultaneously, as more research is being conducted and the opportunities and challenges are better understood, multiple challenges are rising to the top of the discussion, including issues around cultural and racial bias in the development and deployment of algorithms, challenges around algorithmic hallucinations, and general concerns about the safety of AI in therapeutic interventions.
   
   The positive evidence for the value of AI and machine learning has been most convincingly demonstrated in diagnostic medicine, specifically where machine learning is superior to the clinician in performing screening of large amounts of visual imaging datasets in ophthalmology, dermatology, and pathology.
   
   For the life sciences industry, there is emerging evidence of the value of AI in clinical development, especially in enhancing operational efficiencies regarding study design site identification and patient recruitment, pharmacovigilance, clinical monitoring, and patient care.¹¹
   
   However, there are major barriers to broader adoption of AI in drug discovery and development pertaining to key factors such as understanding of the biology of disease, challenges with the quality of data, issues with AI tools such as bias in algorithms, and lack of capabilities in using AI.
   
   To date, no new drug has been developed and approved based on fully AI-generated drug discovery; however, the pipeline of drugs in development with AI-associated platforms are growing. In 2023, at least 19 drugs were in clinical development attributed to AI, and some of these drug candidates may be advancing in the clinical pipeline in 2024.¹²
   
   An indicator of progress for the life sciences sector will be seeing at least 30 drug candidates with AI-based platforms in active clinical development programs in 2024.


6. Bipartisan legislation – Will the average patient out-of-pocket drug cost per retail prescription be lowered by more than 10%?
   
   The 2024 presidential election may be the first since 2008 when healthcare reform and the Affordable Care Act (ACA) – or repeal of the ACA – are not front and center. As we can expect very close election results – possibly with politically divided executive and legislative branches – and the full implementation and implications of the Inflation Reduction Act of 2022 still playing out, further major health policy changes appear to be unlikely.
   
   Instead, important legislation should be expected regarding pharmacy benefits management, where there is broad bipartisan agreement. The legislation, which includes several different proposals, will affect how pharmacy benefit managers (PBMs) negotiate price discounts with drug manufacturers. The intention of the legislation is to shine light on the complex pharmaceutical supply chain and the role that PBMs play as the “intermediaries” between drug manufacturers and patients. The hope is that drug prices will be lowered through increasing transparency, passing on rebates to plan sponsors and/or patients, and reducing out-of-pocket costs for beneficiaries as prices will be tied to net prices instead of list prices.
   
   The success of PBM legislation will ultimately be assessed based on whether it lowers drug prices for patients, since increased transparency in and of itself does not lead to improvement in the supply of drugs to patients.¹³  In 2022, the average final cost per retail prescription was $9.38, while 1.9% of all patients paid more than $1,500 out-of-pocket for their prescriptions. Uninsured patients paying with cash for a branded drug spent an average of $88.71 per prescription.¹⁴
   
   Look for a reduction in the average final cost per retail prescription of at least 10% as a sign of progress for the life sciences sector in bringing necessary medicines to patients at a lower out-of-pocket cost.


7. Disruptors in the delivery of primary care – Will more than 30% of primary care physicians be employed by corporate entities by the end of 2024?
   
   The primary care landscape, which accounts for some $260 billion in annual healthcare spending, is ripe for transformation, fueled by the growth of direct-to-consumer telehealth, vertical integration of the retail healthcare sector, and the rise of “payviders” (integrated financing and delivery systems). Traditional providers are under pressure from new disruptors, including Amazon, Aetna, CVS Health, UnitedHealth Group/Optum, the Walgreens Boots Alliance, Humana, and Walmart, as well as tech companies such as Apple and Google/Alphabet, that have all staked their claim in primary care and are using their platforms to expand their services.¹⁵  As part of this transformation, the number of primary care physicians employed by corporate entities is growing, and from July 2020 to January 2022, the percentage of physicians employed by corporate entities grew from 15.3% to 21.8%¹⁶
   
   In a parallel track, some health insurers are expanding into home care services, aided by advances in digital health and logistics technology, as the centerpiece for transforming the delivery of care. By combining home health, pharmacy, and primary care services, the companies embrace the home as a more convenient setting for individuals, which potentially can lower costs and provide a powerful touchpoint to understand and manage the holistic health of an individual. This also reflects a general belief that home health can be the next frontier in the evolution of value-based medicine.
   
   Many of the business models underlying these changes remain untested in terms of their impact on individual health outcomes, population health, and economic sustainability. And short-term increases in market share do not necessarily translate to sustained success, especially for those players operating in unfamiliar territories.
   
   For the life sciences sector, the impact of these primary care disruptors on the use of medicines is also largely unknown. To the extent these disruptive models are able to bring preventive care – including vaccinations – to more patients, and treat chronic disease more effectively than traditional care delivery, with the provision of multi-disease care and achieving higher adherence rates, they may represent a positive force for the delivery of “the right medicine to the right patient at the right time”. As these well-capitalized businesses pursue their strategies with a goal of transforming the delivery of healthcare, their progress, traction and impact will be important indicators of their potential impact on the life sciences sector.
   
   Will the number of primary care physicians that are employed by health insurers and corporate entities and their impact on medicine use grow to more than 30% in 2024?

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Preparing for the unknown in 2024

While noone can predict what will happen to the life sciences sector in 2024, these seven areas will provide useful signals to the industry as to the nature, pace, and direction of change. It is critically important that life sciences leaders pursue innovation not just at the R&D and product level, but across the entire life sciences enterprise, and also explore new business models, collaborations, and partnerships.

Not surprisingly, important events and issues will likely occur that are not addressed above; however, the more the life sciences industry prepares for tackling the trickiest known issues, the better prepared industry will be to navigate the unknown issues.

Fasten your seat belts.

¹ Illumina Announces Decision to Divest GRAIL, Dec 17, 2023, https://investor.illumina.com/news/press-release-details/2023/Illumina-Announces-Decision-to-Divest-GRAIL/default.aspx
² FDA Approves First Gene Therapies to Treat Patients with Sickle Cell Disease. https://www.fda.gov/news-events/press-announcements/fda-approves-first-gene-therapies-treat-patients-sickle-cell-disease
³ Data & Statistics on Sickle Cell Disease. Centers for Disease Control and Prevention. Last reviewed: July 6, 2023. https://www.cdc.gov/ncbddd/sicklecell/data.html
⁴ Racial and ethnic differences in sickle cell disease within the United States: From demographics to outcomes. Pokhrel A et al. European Journal of Haematology. May 2023. https://pubmed.ncbi.nlm.nih.gov/36710488/
⁵ Issue Brief: Medicaid Barriers to Accessing Cell & Gene Therapies. The Alliance for Regenerative Medicine. November 2023. https://alliancerm.org/medicaid-barriers-to-accessing-cell-gene-therapies/
⁶ Obesity Treatment Rates Increase as GLP-1 Inhibitors prosper. IQVIA.Mar 17, 2023. https://www.iqvia.com/library/white-papers/obesity-treatment-rates-increase-as-glp-1-inhibitors-prosper
⁷ Pipeline of new molecules for obesity. CT.gov. TrialTrove and Pipeline Intelligence. Dec. 2023.
⁸ Obesity: Six trials to watch over the next 12 months. Abigail Beaney. Clinical Trials Arena. June 30, 2023. https://www.clinicaltrialsarena.com/features/obesity-trials-to-watch/?cf-view
⁹ US employers to see biggest healthcare cost jump in a decade in 2024. Leroy Leo and Khushi Mandoware. Reuters, Sept 21, 2023 https://www.reuters.com/world/us/us-employers-see-biggest-healthcare-cost-jump-decade-2024-2023-09-20/
¹⁰ Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Lincoff, Am et al. New England Journal of Medicine. November 11, 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa2307563
¹¹ AI in Clinical Development. IQVIA White Paper, https://www.iqvia.com/-/media/iqvia/pdfs/library/white-papers/ai-in-clinical-development.pdf
¹² Global Trends in R&D 2023. IQVIA Institute. Feb 2023. https://www.iqvia.com/-/media/iqvia/pdfs/institute-reports/global-trends-in-r-and-d-2023/iqvia-institute-global-trends-in-rd-2023-forweb.pdf
¹³ Pharmacy Benefit Manager Transparency Act of 2023. Michael Fiori. IQVIA white Paper. March 29, 2023. Andrea Park. Fiere Biotech, Jul 12, 2023. https://www.iqvia.com/-/media/iqvia/pdfs/us/white-paper/2023/pharmacy-benefit-manager-transparency-act-of-2023.pdf
¹⁴ The Use of Medicines in the U.S. 2023. The IQVIA Institute for Human Data Science. Apr 2023. The Use of Medicines in the U.S. 2023 - IQVIA
¹⁵ Healthcare Disruption: 2023 Outlook. The Buzz Market Scan. February 2023. https://www.aha.org/system/files/media/file/2023/02/The-Buzz-Disruption-Outlook-2023.pdf
¹⁶ A Growing Number of Physicians are Employed. Philip Miller. AMN Healthcare. May 6, 2022. https://www.amnhealthcare.com/blog/physician/perm/a-growing-number-of-physicians-are-employed/