An Injection of Innovation: How Drug Delivery Systems are Changing

New applications and therapies for injectable pharmaceuticals are constantly evolving, bringing the potential for positive patient outcomes

The market for injectable drugs is booming, fueling both a wave of innovation in device design and a debate about the relative pros and cons of injectables versus oral medication. As regulators continue to approve injectable medications that could replace daily pill regimens, particularly long-acting drugs that could improve patient compliance, it is legitimate to ask whether injectables will one day become the norm.

According to the latest projections by Reports and Data [1], the global injectable drug delivery market could reach $1.317 billion by 2030, fueled by the prevalence of life-threatening diseases, the development of smart wearable devices, and the Internet of Things (IoT), which makes it possible to collect valuable data directly from injection devices.

Conventional injectables, prefilled syringes, auto-injectors, and pen-injectors are all expected to become more popular, as the convenience and at-home delivery potential of injectable drugs are pushing pharmaceutical companies to consider more efficient devices for treating chronic and age-related conditions such as diabetes and arthritis. With the COVID-19 pandemic having highlighted the need for improved remote self-administered care, the age of injectables is dawning.

Combating bad cholesterol

Evidence of this trend is easy to find. In 2021, for example, the US Food and Drug Administration (FDA) approved Leqvio (inclisiran) from Novartis, as a first-in-class siRNA to reduce low-density lipoprotein (LDL) levels with long-acting injections. With only two maintenance doses each year, ‘bad’ cholesterol can be kept under control.
Compared to a placebo, Leqvio provides sustained LDL reduction of up to 52% for certain patients with atherosclerotic cardiovascular disease (ASCVD) who are already on maximally tolerated statin therapy. ASCVD is the result of an accumulation of lipids on the inner lining of the arteries. Rupture of this atherosclerotic plaque can cause heart attacks and strokes, which together account for 85% of all cardiovascular disease deaths.

“ASCVD is a substantial public health burden affecting 30 million Americans,” says Norman Lepor, MD, a Los Angeles based cardiologist and a clinical investigator in the Phase III clinical program for Leqvio. “Leqvio works differently than other cholesterol treatments, with twice-yearly dosing that makes it a compelling option for the millions of people already on cholesterol-lowering medications struggling to reach their LDL target.”

Leqvio reduces LDL by boosting the liver’s ability to prevent the production of a protein that helps keep circulating cholesterol levels high. Doing so with only a twice-yearly maintenance dosing schedule could well be a turning point in the treatment of ASCVD, particularly for patients who have difficulty staying on self-administered medicines with greater dosing frequency.

Diabetes is another key target for long-acting injectables. In 2021, a trial led by Harpreet S. Bajaj of LMC Diabetes and Endocrinology Brampton in Ontario, Canada, found that treating people with Type 2 diabetes with a new once-a-week injectable insulin therapy was as safe and as effective as daily injections. For more than a century, diabetes treatment has relied on daily insulin injections, which can be painful, inconvenient and, for some patients, stigmatizing. An effective and safe insulin that can be administered just once a week could, therefore, be considered a major breakthrough.

Rethinking end-of-life care

A recent United Kingdom study by Ben Bowers of the Primary Care Unit, Department of Public Health and Primary Care at the University of Cambridge, noted the importance of injectables in end-of-life care, though there is little transparency around the frequency, timing, and recorded circumstances of anticipatory medications prescribing for patients living at home and in residential care.

“Health professionals are keen to plan for last days of life care and put in place advanced prescriptions to ensure the person receives timely symptom control,” says Bowers. “This is to support terminally ill people, and their families, in their wishes to have end of life care at home. Without this proactive planning, it can take several hours to access prescriptions and source injectable medications if people have painful and distressing symptoms and are no longer able to swallow oral medications.”

“Many patients never need to have injectable medications started but having them available in the home is intended to provide reassurance to all involved,” he adds. “Advanced prescribing of injectable medications for symptom control in the last days of life originally started for people dying from advanced cancer. It has quickly grown to be a common intervention for patients dying from a wide range of terminal conditions. My recent research found prescriptions were in place for half of people dying from expected causes in the community.”

Though the issue of advanced prescribing can be a controversial one, it does highlight the potential advantages of injectable medications, including morphine for pain control and midazolam for managing agitation, which can remain accessible in the home for weeks or months [2].

“The subject of advanced prescribing should be used as an opportunity to hold open and honest conversations about families’ concerns and the realities of dying,” Bowers remarks. “Practice is based on doctors’ and nurses’ assumptions and experiences that the availability of injectable medication in the home for last days of life care provides reassurance to all involved. Our new research has found injectable medications are simultaneously reassuring and a source of unease to patients and their families.”

New breed of device

There is no shortage of new ideas for innovative injectable therapies. For instance, researchers at the University of Liverpool have recently demonstrated the potential of repurposing an existing and cheap drug into a long-acting injectable therapy to treat COVID-19. The university’s Center of Excellence for Long-acting Therapeutics (CELT) showed that the nanoparticle formulation of niclosamide is a scalable long-acting injectable antiviral candidate. CELT scientists formed redispersible solid drug nanoparticle formulations of niclosamide that can be stored as solids, reconstituted with water, and utilized as injectable therapies.

In terms of device design, there is also a wave of innovation, especially to help patients adhere to drug regimens. Connected injectables are on the rise. Novo Nordisk, for example, has developed the NovoPen 6 and NovoPen Echo Plus devices—smart insulin pens that automatically record insulin dosing information.
During the pandemic, when there arose an increased need for remote patient care, health care providers ramped up their efforts to deliver new ways to improve the management of chronic conditions, as well as reduce costs. Encouraging self-administered care and putting patients in control of their own treatment is precisely what connected injectables devices can do.

“Connected drug delivery devices play an important role in helping biopharmaceutical manufacturers understand and track key trends in patient adherence,” says Matthew Schabacker, vice president and general manager of Advanced Drug Delivery Solutions at Global Medical Technology Company BD.

Currently, BD is working to integrate its UltraSafePlus Passive Needle Guard system with Biocorp’s Injay Technology to capture and transmit self-administered injection data using near-field communication (NFC) technology and sensors to identify the product. The system confirms when a complete injection has taken place and sends that data to a smartphone app [3].

Such solutions are typical of the wave of innovation that is driving the global connected drug delivery market, which could see at double-digit growth rates over the next decade. That said, changing a drug’s primary package is not always a simple process. It can cost millions and may take years to validate or revalidate container closure integrity, biocompatibility, stability, reformulation, extractables and leachables, and a host of other parameters.

As a result, pharmaceutical companies have often fallen back on existing delivery systems that may not be the best fit for a new application. Now, with the range of potential uses for injectables growing so rapidly and connected technology so effective in enabling remote monitoring of self-medication programs, investing in injectables innovation will soon become an imperative [4].

References

1. “Pharma and healthcare—Injectable drug delivery market,” Reports and Data, Tech. Rep. RND_001382, Apr. 2023. [Online]. Available: https://www.reportsanddata.com/report-detail/injectable-drug-delivery-market
2. B. Bowers, K. Pollock, and S. Barclay, “Unwelcome memento mori or best clinical practice? Community end of life anticipatory medication prescribing practice: A mixed methods observational study,” Palliative Med., vol. 36, no. 1, pp. 95–104, 2022, doi:10.1177/02692163211043382.
3. J. McAdory, “Big data research reveals 60 percent of injectable medication users fail to follow instructions,” Harbert College of Business, Auburn Univ., Auburn, AL, USA, Jul. 2016. [Online]. Available: https://harbert.auburn.edu/news/Bigdataresearchhelpspharmaceuticalindustry.html
4. “Connected drug delivery devices market size, share & trends analysis report by product, by route of administration (parenteral, inhalational), by application (asthma, COPD, diabetes management, others), by region, and segment forecasts, 2023–2030,” Grandview Research CDDD Market, Tech. Rep. GVR-2-68038-651-6, accessed: 2023. [Online]. Available: https://www.grandviewresearch.com/industry-analysis/connected-drug-delivery-devices-market