In 2015, sales of AbbVie’s biologic
treatment for rheumatoid arthritis and related autoimmune diseases, Humira, topped
$14 billion. Another 39 biologics also reached blockbuster status, exceeding $1
billion in sales according to Morningstar. Nine of these biologics brought in
$5 billion in global sales.
Given the potential — both therapeutic
and financial — it comes as no surprise that some 900+ biologics are currently progressing
through pharmaceutical companies’ R&D pipelines. This year, these large
molecule, protein-based therapeutics continue to be the main drivers of
industry growth and are predicted to reach $445 billion in sales by 2019, up
from $289 billion from 2014.1
However, biologic drugs consist of
mega-molecules that are hundreds of times the size of conventional small
molecule drugs. They are frequently composed of a heterogeneous mixture of more
than 1,300 weighty amino acids. That creates three main challenges for
pharmaceutical companies seeking to develop the next blockbuster biologic:
1. They are hard to make2
2. They are hard to take
3. They can be expensive
Despite these difficulties, targeted
as they are to particular genes or proteins, biologics are compelling for
treating diseases due to their higher specificity and fewer side effects.3,4
Biologics on the market and in
development are also broad ranging, suitable for treating a large number of
disparate diseases. Currently, cancers and related conditions are the most researched
area for biologics, according to analysts. Other prominent target diseases are
autoimmune diseases, blood disorders, and genetic disorders. The list includes,
but is not limited to:
-Sickle cell anemia
-Crohn’s disease, ulcerative colitis,
and other digestive disorders
-Duchenne muscular dystrophy, Pompe
disease and other genetic diseases
-Infectious diseases, such as HIV, Ebola,
and CMV diseases
Clearly, opportunity abounds. To take advantage
of it, the most proactive biopharma companies are turning to new drug delivery
technology that may help dissipate top challenges and at the same time, create
demand for their products and improve compliance. Yes, new drug delivery
technology can help tackle development, delivery, and cost challenges.
PHARMAS ARE EXPLORING THE NEW DELIVERY OPTION
Why change the way pharmas create and
administer drugs now? Because pressures have increased and because ultimately
it’s likely to pay off. Despite optimism that molecules in R&D could potentially
turn to biologics gold, pharmaceutical executives are under tremendous
pressure. They must reduce costs. They need to increase efficiency. Margins are
eroding, and now they also have to prove the value of their expensive biologic
drugs as the healthcare system moves inexorably toward value-based care.
These rapid changes are testing long-held
industry beliefs. As a result, forward-thinking pharmaceutical companies are responding
by employing entirely new operational models and adopting new tools that can
better position them to succeed in the rapidly emerging outcomes-based
These changes in the way pharmas do
business are imperative – but promising. Data show that the most innovative
pharma companies prosper most. Top innovators saw 25% of revenues coming from
new products or services versus 14% for less-innovative pharmas. And the
majority of pharma executives surveyed said innovation is a competitive
So in addition to various IT infrastructure
and R&D informatics upgrades, pharmaceutical companies are turning to patient-focused
technology. For example, they are exploring combining their biologic drugs with
the newly available, more advanced wearable high-volume drug delivery devices.
In conjunction with creating new treatments, they are simultaneously reaching
out to similarly innovative drug delivery partners to assure that once the new
drugs reach the market, their value proposition is realized and patients take
them, a requisite for improved outcomes.
As a result, partnerships with companies
developing new connected wearable large-volume injectors are rapidly
proliferating, and more biologic-device combos are expected to gain regulatory
Companies with biologics already on the
market are also looking at new drug delivery technology as they plan their patent
extension strategies. Eleven established biologic products – representing 48%
of total biologic sales – are slated to lose patent protection by 2022.1
LARGE-VOLUME INJECTORS REDUCE FORMULATION TIME & EFFORT
Scientists developing biotherapeutics spend
enormous time and effort on
formulation – sometimes years. This amount
of time and effort can be significantly reduced with use of the newest biologics
delivery technology, the on-body delivery systems now available for clinical
studies and commercial use.
These wearable large-volume injectors
bring to market a novel product development aid that reduces formulation time and
effort by enabling a simpler method of product preparation. Formulation teams
can take advantage of the innovative delivery technology to speed development
of stable, bioavailable, clinically relevant formulations. Formulation teams
can also facilitate patient self-injection of biologics by adopting drug
delivery technology that aids in:
-Delivering more volume of product
-Delivering much higher viscosities caused
by higher concentration of proteins
-Resolving biologics’ greater
propensity to precipitate out of solution
The time and effort savings are
accomplished with automated lyophilization, which accelerates or eliminate
tedious, time-consuming formulation functions for more rapid – and less costly
- product development. In addition, the requirement for formulation teams to
concentrate the product in the smallest possible dose for delivery by an auto-injector
(typically < 1 ml) may no longer be relevant. The latest generation of
injectors has the ability to provide a comfortable injection experience for
higher volume product delivery. Patient acceptance of new higher volume on-body
delivery systems should be high because the devices support mobility, are easy
to use, and minimize any injection discomfort.
TECHNOLOGY: REMOVING COMPLEXITY
The medical literature leaves little
doubt that taking medication as prescribed and for the recommended time period
is problematic for many patients and can significantly impact healthcare outcomes
and cost of care. A World Health Organization (WHO) report cites non-adherence
as a leading cause of preventable morbidity, mortality, and cost.6 Yet,
compliance among chronic disease patients averages just 50%. The WHO report
cites complexity among the major causes of failure to comply with prescribed
Reducing this complexity and its associated
cost is another major challenge facing the pharmaceutical and biotech companies
developing the biologics, monoclonal antibodies, and immunoglobulins that are
revolutionizing treatment of cancers and chronic diseases.
The most advanced wearable large-volume
injectors, such as the Enable Injector, are designed to eliminate complexity entirely
so that the promise of new and existing products is realized, potentially
helping create tomorrow’s blockbusters. Patient confusion and errors are minimized
by requiring only a few simple steps:
- INSERT a standard drug vial/syringe/cartridge
into the transfer system, which automatically warms any refrigerated product in
the 30-40 seconds it takes to fill the on-body delivery system
- PLACE the injector on skin
- PULL the safety tab
- PRESS one button
A large pharmaceutical company’s patient
panels testing a range of injectors strongly favored the Enable Injector,
citing its small size, ease of use, convenience, and “cool” shape among the
reasons for their choice. The findings are replicated in a small clinical trial
with a different cohort.
PATIENTS, BIOLOGICS ARE NOW EASY TO TAKE
On-body delivery systems will also change
the way patients think about injections. Subcutaneous injection remains the
preferred method of delivering injectable drugs, including biologics. Yet,
historically injectable drug administration has been particularly problematic,
in large part because most patients dislike injections, especially those that
are self-administered. Injecting biologics would be even more difficult for
patients due to the large biologics doses required and their viscosity. Legacy
systems, such as syringes and earlier large-volume injectors, could not handle anywhere
near the large doses of up to 50 mL or their viscous formulations.
But now, such large doses are possible
for patients to self-inject easily and comfortably. Today’s wearable high-volume
injectors offer safety, ease of use, and injection comfort - vital attributes
if uncomplicated self-injection of biologics is to gain traction. And now the
injector technology is connected and can monitor compliance, potentially a
major step in improving treatment outcomes.
Fulfilling the vision of
self-injection that is safe, easy, comfortable, and convenient for patients,
yet cost effective for the pharmaceutical industry and payers, today’s most
sophisticated drug delivery devices are distinguished by the following:
standard vials, syringes, or cartridges so no change to the primary container
is required. This eliminates additional time-consuming and expensive stability
warm the drug as the injector fills, reducing the typical 30-minute or longer
wait time to use a refrigerated drug to seconds.
lyophilized drugs, completely automate mixing and reconstitution, removing any
patient variability from the mixing process.
only standard intravenous-set materials in the drug delivery path, minimizing short-term
material-drug compatibility issues.
a small needle size to optimize injection comfort.
small in size with a low profile that can discretely be worn on the body,
eliminating the problems and inconvenience associated with carrying larger, heavier
devices while ambulating.
friendly – no electronics or batteries to remove or recycle.
volume of materials and packing less than that for a standard IV set.
subcutaneous injection up to 50 mL.
drug delivery rate, duration, volume, and needle size for creation of a much
improved patient injection experience
Will these factors boost compliance? Overall
drug regimen compliance has historically been low, and any improvement would
benefit both patients and drug makers. It remains to be seen whether using new
injectors, patients with chronic conditions prescribed injectable biologics are
more likely to keep taking their medications for potentially improved outcomes
and far less drug wastage. Connectivity can be helpful in that assessment.
It looks promising. Among the key attractions
of the newest on-body delivery systems: with never a needle in sight, patients
like using them, removing the many barriers to compliance that have vexed the
industry for decades.
LARGE-VOLUME INJECTORS CAN REDUCE COSTS SIGNIFICANTLY
For payers, patients, and prescribers,
one problem with biologics is their cost, especially as they are often used to
treat chronic conditions, such as rheumatoid arthritis. Whereas a small
molecule drug costs on average $1.00 per day, with a generic drug costing just
cents, a biologic drug costs on average $22 per day.7
In addition to the cost of the drugs themselves,
delivery location can add substantially to the price tag. Almost all biologics
currently require delivery via infusion or injection, traditionally in a hospital
setting, administered by a healthcare provider. The added costs of drug delivery
in a health facility can be astronomical. A New York Times article, Even
Small Medical Advances Can Mean Big Jumps in Bills, cited a $133,000 charge for
a single infusion for psoriatic arthritis at a hospital outpatient clinic – of which
the insurer paid $99,593.
The new technology offers a new, lower
cost delivery option: uncomplicated, comfortable self-administration of
biologics by patients in the comfort of their home, office, or in transit with
the added bonus of giving patients the ability to move freely during treatment.
It also could eliminate the inconvenience and costs incurred by patients. For
example, a breast cancer patient prescribed Herceptin has to travel to a health
facility for a 30- to 90-minute IV infusion. Using a wearable large-volume injector,
the same dose can easily and comfortably be self-administered by the patient at
home, work, or on the go in just a few minutes.
As a result, wearable high-volume injectors
have the ability to move drug delivery from healthcare facilities into the home
or workplace and from health provider-mediated injection to patient self-administration.
This could significantly reduce overall health system costs and for patients or
caregivers, the benefit of no longer needing to travel for treatment, even if only
as an option for inclement weather or other inability to travel, is enormous in
The new, most advanced wearable large-volume
injectors available now for clinical trials and commercial application are
designed to address the challenges of formulating biologics, delivery complexity,
patient compliance, and cost. For patients, they promise a more convenient, comfortable,
and less stressful way of delivering large-volume medications that treat
serious medical conditions and rare diseases.
It is widely anticipated that the most
sophisticated new wearable injectors, those designed on the basis of multiple human
factors studies and preferred by patient panels, will perform these functions:
injectable drug administration significantly
high-volume and/or viscous drugs subcutaneously
cost of drug development by reducing development times
patients to inject easily at home, at work, or on the go
some infusions (particularly those administered in a hospital setting),
significantly reducing the high costs of provider-mediated drug delivery
or eliminate needlestick injuries by removing needles from sigh
with fitness wearables, employ connectivity to provide data
One of the greatest promises of on-body
delivery systems uptake, and the reason they will be rapidly and widely adopted,
is that by creating value on several fronts, they have the potential to help
lower healthcare costs substantially as patients no longer need to visit a healthcare
facility for large-volume drug administration.
1. 2016 Global Life Sciences Outlook. Deloitte.
2. Going Large. The Economist, January
3. Espiritu MJ, Collier AC, Bingham,
JP. A 21st-century approach to age-old problems: the ascension of biologics in
clinical therapeutics. Drug Discovery Today. 2014;19(8):1109-1113.
4. Cai W, Wang Y, Xia R, Gao F. Closing
the gap between preclinical biologic development and clinical application in
rheumatoid arthritis. West Indian Med J. 2015;64(3):312-313.
5. Managing Innovation in Pharma.
Price Waterhouse Cooper (PWC);2013.
6. The World Health Report – Shaping the
7. Generics and Biosimilars
Initiative. Opportunities for biosimilar development: Pro Pharma Communications
To view this issue
and all back issues online, please visit www.drug-dev.com.
Michael D. Hooven is President and CEO,
Enable Injections, LLC. He has over 30 years of experience in the medical device
industry in a broad variety of business, technical, and clinical areas. He is
the Founder of five medical device companies and holds over 100 issued and pending
US patents. Mr. Hooven is the Founder and a Director of AtriCure, Inc. (NASDAQ:ATRC),
where he previously held positions as the Chairman and CEO. He is also Founder
and Chairman of Enable Medical, a surgical device manufacturer that was
acquired by AtriCure in August of 2005. Prior to Enable Medical, he was
Director of Product Development at Ethicon Endo-Surgery from 1988 to 1994,
where he had responsibility for all in-house product development and supervised
a staff of 200 engineers. He held Engineering positions in pacemaker and lead
development at Siemens/Pacesetter from 1986 to 1988 and at Cordis Corporation
in neurosurgical products from 1981 to 1986. In addition, he is Director and
past Chairman of BioOhio, a state-funded organization to accelerate
life-science startups in Ohio. He earned his BSc in Physics and a MSME in
Mechanical Engineering from the University of Michigan.