Large volume injectors (LVIs) are predicted to have significant impact on the parenteral drug delivery landscape. To date, the case for LVIs has focused upon ability to deal with viscosity and
volume challenges associated with administration of biologics. However, LVIs are well positioned to fulfil broader demands as this presentation describes.
1. Wearable Injectors: Would the Real Driver Please Stand Up?
James Blakemore PhD
Senior Consultant, Market Strategy | Cambridge Consultants Ltd
2. ▪ Large-volume injectors (LVIs) predicted to have significant impact on
parenteral drug delivery landscape
▪ To date, case for LVIs has focused upon ability to deal with viscosity and
volume challenges associated with administration of biologics
▪ LVIs well positioned to fulfil broader demands:
o Improve drug efficacy, safety, tolerability
o Reduce HCP or patient workflow
o Facilitate patient self-adminstration
o Product differentiation
Introduction
3. ▪ Derive insights into wider benefits that LVIs may
facilitate by looking at:
o Marketed and pipeline combination products
o Related trends in other therapy areas
▪ Review drivers of LVI beyond volume / viscosity:
1. Slow release
2. Timed release
3. Patient-self administration
4. Reduce dosing frequency
5. ‘Smart’ systems, i.e. not just a connected LVI
LVI Benefits in Combination Medicinal Products | Overview
4. ▪ Slow release of drug product will drive use of LVIs
o Infusion site reactions a common issue with biologic formulations
o Narrow delivery window due to drug PK/PD profile
o Therefore, such therapies administered by slow, controlled infusion
▪ Ability to transfer these types of formulations into a suitable LVI that delivers
its dose at controlled flow rate may enable ambulatory drug delivery
▪ Trevyent® (SteadyMed Therapeutics; San Ramon, CA)
o Reformulation of treprostinil in PatchPump® device for treatment of PAH
o Permits slow release of drug; positioned to minimise risk of infusion site reactions
– a common side effect of the drug when administered by infusion line
Slow Release
Image taken from https://www.steadymed.com/technology
5. ▪ Other therapies could leverage slow release via LVI:
o Oncolytic drugs, small molecule / biologic therapies
o Parkinson’s disease (apomorphine); short drug half-life
requires continuous infusion at controlled rate
▪ Secondary benefit; reduction in HCP workflow
o Mitigate preparation, administration of drug
▪ Approach requires non-trivial formulation technology,
bridging studies to support transition
Slow Release (continued)
6. ▪ Timed – or delayed – release of medicinal products is well-established
▪ Translating principle across to biologic therapies technically challenging
▪ Neulasta® Onpro™ (Amgen; Thousand Oaks, CA)
o Pegfilgrastim for the treatment of chemotherapy-induced neutropenia
o System consists of drug in a single-use on-body injector
o Designed to delay administration for up to a day post-chemotherapy
so drug can exert therapeutic effect at right time
▪ System avoids need for patient to re-present to physician
o Mitigates dose limiting side effects typically associated with chemotherapy
Timed Release
Image taken from https://www.neulasta.com/onpro/
7. ▪ Other therapies could leverage timed release via LVI
o Interferon alfa (Hepatitis B/C) requires weekly SC dosing;
label “…injections should be administered in the evening…”
o 5-HT3 agonists (CINV); complex dosing schedule requires drug
before start of chemotherapy, after the first dose, then bid. for 2d
o Pre-programmed LVI could administer single doses at specific
time or several doses over prescribed schedule
▪ Need to demonstrate overall reduction in cost of care
Timed Release (continued)
8. ▪ Certain care pathways require patient to present to infusion clinic on a
regular basis over an extended period to receive therapy
▪ Once maintenance therapy established, requirement becomes burden
▪ Patients self-administration in home environment would reduce burden
▪ Herceptin® SC (Roche; Basel, Switzerland)
o Proprietary Single Injection Device (SID) platform with novel excipient
▪ Reduced drug preparation and administration time in the infusion clinic,
compared with infused presentation1; positive commercial impact
Patient Self-Administration
1 De Cock et al (2016) Cancer Med 5 (3), pp 389-397
Image taken from poster presentation Gligorov et al (2012)
Presented at ESMO, 28 September–2 October 2012, Vienna
9. ▪ Other therapies that could leverage patient
self-administration by LVI
▪ Oncology
o Injectable hormone analogues, e.g. goserelin
o Administered SQ monthly (or 3 monthly) into
abdomen wall by HCP; to several years treatment
o Once maintenance therapy established could move to
LVI presentation for patient self-administration
▪ Disruption to care pathway; would physicians adopt?
Patient Self-Administration (continued)
10. ▪ Common for novel therapies with similar mechanisms of action to receive
broadly concurrent approval times
o Difficult for manufacturers to establish material basis for differentiation
▪ Favourable dosing frequency may be principal route to differentiate
o Proof of improved outcomes data may push therapy towards first line
▪ Repatha® Pushtronex™ (Amgen; Thousand Oaks, CA)
o Comprises medicinal product packaged in LVI design variant
o System provides monthly dosing as adjunct for statin therapy
Reduced Dosing Frequency
Image taken from http://www.amgen.com/
11. ▪ Utilise real estate on LVI to add functionality
▪ Combine in vitro diagnostics,
algorithm development
and connectivity
▪ Make real-time decision on:
o Dosage administration (mg/kg)
o Flow rate (mg/kg/hr)
o Emergency cut-off
o SOS call
o Therapeutic drug monitoring…
…towards closed loop/hybrid system?
‘Smart’ LVI Systems: Not Just a Connected System
00.0 kg
Diagnostic
measurements
Healthcare professional
monitoring and intervention
Mum
Device configuration,
asset management
Assistance
requests
Drug
compliance
12. ▪ LVIs have potential to address wider set of clinical
and commercial benefits beyond volume/viscosity
▪ Principles demonstrated in case studies apply to
other therapy areas, particularly chronic diseases
▪ Formulation technologies key to facilitate shift from
IV to SC
▪ Payers may not acknowledge value of LVIs until
functional benefits translate into significant
improvement in patient outcomes
Conclusion: Benefits of Greater Diversity in LVI Design
13. ▪ Exploration of benefits applicable to innovator
biopharmaceutical development and generics
▪ We should not expect current crop of LVIs to
satisfy broad range of clinical needs
▪ Rapid expansion in the LVI class,
including more bespoke design variations of
existing platforms, in order to meet these needs
Conclusion: Benefits of Greater Diversity in LVI Design (continued)
