The top three global therapy areas by value are dominated by parenteral products, which in 2024 held a share of sales of 57% in oncology, 89% in immunology and 58% in diabetes. Parenterals account for over 96% of the value of obesity, the fastest growing therapy area, and have been driving its extraordinary growth in recent years. Other therapy areas with a noteworthy presence of parenteral drugs include antibacterials, pain, respiratory, mental health and anti-thrombotics, with parenteral value share ranging from 14% to 53%.

We also find many parenteral products among the pharmaceutical industry’s best-selling brands, e.g., immunology blockbusters Humira, Stelara, or Dupixent; checkpoint inhibitors Keytruda, Opdivo; insulins like Lantus, Tresiba or Humalog; or incretin mimetics Ozempic and Mounjaro to treat diabetes, and their counterparts Wegovy and Zepbound which are propelling the surging obesity market.

Parenteral medicines are dominated by injectables representing 81% value share, which include subcutaneous, intramuscular, intradermal and intravitreal, ophthalmic injections, with infusions accounting for the remaining 19%. The segment of self-administered parenteral products has grown at 15% 5-year CAGR, twice the rate of parenteral products requiring administration by a healthcare professional, often in a hospital setting, and in 2024 represented 60% of parenteral market value.

However, there is a downside to parenteral drugs. Their administration, especially if frequent, represents a burden on both patients and health systems, including disrupting patients’ life, potentially leading to non-adherence; health system infrastructure and capacity requirements, the need for qualified staff for HCP administered drugs, and incremental cost, e.g., a cold chain for storage and delivery, or managing waste from single-use devices such as injector pens.

Therefore, long-acting injectables, in particular those requiring significantly less frequent administration, hold great promise for alleviating this considerable burden on patients and health systems to facilitate the broad adoption of these important, novel therapies.

From long-acting to ultra long-acting injectables

The FDA approved the first long-acting injectable (LAI) in 1952, antibiotic penicillin G benzathine (Bicillin LA), for intramuscular injection every second or fourth week. Over the following decades, LAIs were developed in other therapy areas, including depot formulations as contraceptives, hormone replacement or hormone-based therapies for breast and prostate cancer, and long-acting antipsychotics for the treatment of schizophrenia. However, these early successes with LAIs were all based on small molecule drugs.

Today’s injectables predominantly are much more complex therapeutics based on peptides, biologics and advanced modalities, with much greater sensitivity to their environment, more challenging pharmacokinetics and physical properties, which, for example, translate into higher injection volumes and viscous formulations.

Despite these formidable challenges, innovators have been making strides towards substantially reducing the frequency of administration to give rise to ‘ultra long-acting injectables’ (u-LAIs) – with dosing required once a quarter or even less often (see Figure 2).

Noteworthy examples of such ultra long-acting injectables that are on the market include several biologics across a range of therapy areas, such as:

• Psoriasis: Self-administered, subcutaneous IL-23 inhibitor Skyrizi requires only quarterly maintenance dosing.
• Migraine: Self-administered, subcutaneous CGRP inhibitor Ajovy requires only quarterly maintenance dosing.
• Ophthalmology: HCP administered, intravitreal VEGF-A and PlGF inhibitor Eylea and VEGF and Ang-2 targeting bi-specific antibody Vabysmo require maintenance dosing only every 4 months in certain patients with neovascular (wet) age-related macular degeneration (nAMD).
• Osteoporosis: HCP administered, subcutaneous RANKL inhibitor Prolia requires an injection only every 6 months.
• Multiple sclerosis: HCP administered, subcutaneous CD20 targeting, B-cell depleting Ocrevus requires an injection only every 6 months.

We also find several small molecule based examples among marketed, ultra long-acting injectables, which highlight the continuing innovation in extending dosing intervals for the original LAIs, e.g.,

• Contraception: Medroxyprogesterone acetate, an example of a Long-Acting Reversible Contraceptive (LARC), is available in two long-acting formulations for quarterly injection: Depo Provera, for intramuscular HCP administration, and Sayana Press, for sub-cutaneous self-administration.
• Schizophrenia: HCP administered, intramuscular dopamine Type 2 (D2) and serotonin Type 2 (5HT2A) receptor antagonist paliperidone palmitate is now available in two ultra long-acting formulations Invega Trinza and Invega Hafyera, which are administered quarterly and every 6 months, respectively.
• HIV pre-exposure prophylaxis (PrEP): HCP administered, subcutaneous HIV-1 capsid inhibitor Yeztugo was approved in June 2025 as the first and only, twice-yearly injectable pre-exposure prophylaxis. Furthermore, its active ingredient, lenacapavir, is in development as once-yearly, intramuscular PrEP and has shown promising early results in a phase 1 trial: Median plasma concentrations for once-yearly intramuscular lenacapavir exceeded those associated with efficacy in phase 3 studies of twice-yearly subcutaneous lenacapavir for PrEP for at least 56 weeks [2].
  In July 2025, the World Health Organization updated its HIV prevention guidelines to recommend Yeztugo [3], with its Director-General describing lenacapavir as the “next best thing” in the absence of an HIV vaccine.

As the last example illustrates, when dosing intervals become very long and approach once-yearly administration, the boundaries between therapeutics and vaccines begin to blur, particularly in the case of prophylactics. While some vaccines provide life-long, or at least decade-long protection, others such as influenza or COVID require annual administration, the same frequency we are beginning to see with the most durable long-acting injectables.

This has implications for the positioning of ultra long-acting injectables and the dialogue with health systems about the clinical and economic value of such therapies.

Ultra-long acting injectables with very low dosing frequencies such as twice or once a year could also redefine patient convenience and potentially upend patients’ typical preference for oral therapies, where such alternatives exist, which often require daily dosing.

Finding differentiation via extended dosing intervals

In crowded therapy areas, the need for less frequent injections may serve as a source of differentiation by offering greater convenience to patients and HCPs.

In psoriasis, for example, Skyrizi’s quarterly dosing schedule as maintenance therapy sets it apart in a busy competitive field, where fellow IL-23 inhibitor Tremfya and IL-17 inhibitor Bimzelx require self-injection every 8 weeks while IL-17 inhibitors Taltz and Cosentyx are self-administered every 4 weeks. Meanwhile, Oruka Therapeutics is working on reducing injection frequency even further with its phase 1 IL-23 inhibitor ORKA-001, offering potentially twice-yearly or only once-a-year dosing.

In the earlier example of HCP administered, injectable HIV pre-exposure prophylaxis (PrEP), the twice-yearly dosing of recently approved Yeztugo clearly differentiates it against incumbent PrEP Apretude, which requires injections every other month.

In several other therapy areas with entrenched competitors we find that later entrants seek differentiation via significantly extended dosing intervals vs. incumbents, for example (see Figure 3):

• Atopic dermatitis: Apogee Therapeutics is developing subcutaneous IL-13 inhibitor APG777 with an extended half-life which is being investigated for maintenance dosing by self-injection every 3 and 6 months. This compares to dominant, first-to-market therapy IL-4/13 inhibitor Dupixent being self-injected every 2 weeks, and subsequent market entrants IL-13 inhibitors Adtralza and Ebglyss requiring self-injection every 2 and 4 weeks, respectively.
  Meanwhile, Astria Therapeutics is investigating in a phase 1 trial the potential of OX-40 antagonist STAR-0310 for self-injection every 2-3 months.
• Asthma: GSK’s ultra-long acting IL-5 inhibitor depemokimab has been submitted to the FDA as add-on maintenance therapy of asthma with twice-yearly, subcutaneous self-administration. This compares to the following dosing schedules of incumbent, self-administered biologic asthma therapies: every 2 weeks for Dupixent, every 2 weeks and 4 weeks for first-generation IL-5 inhibitors Nucala and Fasenra, respectively, and every 4 weeks for most recent market entrant TSLP inhibitor Tezspire.
• Cardiovascular: RNA interference to "silence" gene expression for specific proteins inherently lends itself to delivering a durable response, as exemplified by several RNAi therapeutics for cardiovascular diseases.
  Leqvio (inclisiran), a small interfering RNA (siRNA) agent directed at PCSK9, is approved as a twice-yearly, HCP administered injection for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH). For comparison, first generation PCSK9 inhibitors, monoclonal antibodies Praluent and Repatha, require self-injection every month, whereas the latest PCSK9 inhibitor recaticimab, recently approved in China, can be self-injected every 2 months.
  Another small interfering RNA agent, Roche/Alnylam’s zilebesiran, is in development as a durable therapeutic for controlling hypertension, by silencing the angiotensinogen gene in the liver, which requires a twice-yearly, HCP administered injection.
  Sirius Therapeutics is moving its early-stage, factor X protein expression targeting siRNA candidate SRSD107 into phase 2, as next-generation anticoagulant for thromboembolic disorders with the potential for twice-yearly or even once-yearly administration.
• Obesity: The unprecedented consumer-led demand for weight loss medicines has attracted many players to this opportunity, resulting in a pipeline of over 170 assets in development, of which 54% are self-administered, subcutaneous injectables. On-market mega-blockbuster brands Wegovy and Zepbound/Mounjaro require weekly injections, which is also the typical dosing frequency for many injectable obesity pipeline assets.
  However, some companies are looking to extended dosing intervals as a differentiator in what will become an increasingly crowded future obesity market. For example, Amgen is developing MariTide, a long-acting, bispecific GLP-1 receptor agonist and GIP receptor antagonist, for monthly and possibly less frequent self-injection; biotech company Metsera, founded with an explicit focus on developing ultra long-acting therapies for obesity, is investigating injectables GLP-1 receptor agonist MET-097i and amylin analogue MET-233i, both for monthly dosing.

These examples illustrate how ultra long-acting injectables have the potential to disrupt established practice and re-set patient and HCP expectations for convenience.

However, it is important to note that differentiation via extended dosing intervals alone will not be successful. Firstly, ultra-long acting injectables need to be very safe, with a very clean side effects profile, because once administered they cannot be reversed. As for efficacy, as a minimum, these new entrants will need to match incumbents because patients and HCPs are unlikely to accept any material convenience/efficacy trade-off, whereas payers will be reluctant to grant market access to a new therapy offering extended dosing intervals combined with sub-par efficacy in a market with more potent alternatives.

Final thoughts

Ultra long-acting injectables (u-LAIs) deliver significant benefits to patients and health systems by reducing the burden of frequent drug administration. However, for ultra long-acting injectables to enjoy broad success they must overcome a number of challenges:

• Patients and HCPs may perceive u-LAIs as ‘irreversible therapies’, leading to potential concerns that they cannot be easily discontinued or adjusted once initiated.
• Very long dosing intervals may create a new type of adherence problem, especially for self-administered u-LAIs, e.g., not allowing patients to establish a routine and instead requiring longer term, forward planning of treatment schedules.
• Consumed volume for u-LAIs per drug treated patient is inevitably lower than for more frequently administered therapies. Innovators therefore will require a higher unit price to earn a comparable return. Payers may apply a narrow definition of value and push back on perceived, unjustified premium pricing vs. benchmarks based on established, more frequently dosed therapies, possibly with the same MoA and delivering similar clinical outcomes.

Evidence and patient support will be critical to address these challenges. Firstly, innovators must demonstrate unique clinical and economic value in routine clinical practice, including evidence for real word effectiveness and safety, beneficial HCRU impact and potential cost offsets. Secondly, patient support, including digital tools, will be key to help patients manage extended dosing intervals, e.g., longer term treatment scheduling, treatment reminders and timely drug supply, in particular for u-LAIs requiring a cold chain.

Parenteral medicines including injectables, its largest sub-category, are at the heart of future therapeutic innovation and represent the fastest growing formulation segment. Ultra long-acting injectables, with their promise of alleviating the burden of drug administration associated with this innovation wave, are well positioned to seize the momentum.

References:

1. Global trends in R&D 2025; IQVIA Institute report: https://www.iqvia.com/insights/the-iqvia-institute/reports-and-publications/reports/global-trends-in-r-and-d-2025
2. Jogiraju, Vamshi et al., Pharmacokinetics and safety of once-yearly lenacapavir: a phase 1, open-label study; The Lancet, Volume 405, Issue 10485, 1147-1154; https://doi.org/10.1016/S0140-6736(25)00405-2
3. WHO news release, 14 July 2025: WHO recommends injectable lenacapavir for HIV prevention