Pharma intelligenceinforma
Pharma intelligenceinforma
Taking the High Out of Pain: Exploring Abuse-Deterrent Opioids and Opioid Alternatives
More than 650,000 opioids are dispensed in theUS with nearly 4,000 people consuming a prescriptionopioid for non-medical use, leading to 78 deaths each day from an opioid-related overdose.
The opioid epidemic has reached an "all-hands-on-deck" level of urgency requiring interdisciplinary intervention.
Exploring the landscape of abuse-deterrent opioid formulationsAbuse-deterrent formulation (ADF) technology is expected to meaningfully deter abuse by making drugs more difficult to tamper with or less rewarding.
Between 2010 and 2016, much effort was invested in the development of abuse-deterrent opioids.
Since 2010, the US Food and Drug Administration (FDA) has approved at least 12 drugs with abuse-deterrent characteristics, but not all are available on the US market.
Physical/chemical barriers
Agonist/antagonist combo
Prodrug
ADF Category
FDA APPROVAL YEAR
Acurox Acura/Eaglet FDA Approval
2012 20132011 2014 2015 2016 2018
Acurox (Acura/Eaglet) 2012 Launch
Zohydro ER (Pernix)
2014 Launch
Embeda (Pfizer)
2014 Launch
Targiniq ER(Purdue)
Not launched
Zohydro ER abuse deterrent
(Pernix) 2015 Launch
Hysingla ER (Purdue)
2015 Launch
Oxycontin (Purdue)
2013 Launch
Vantrela ER (Teva) Ceased
Xtampza ER (Collegium)
2016 Launch
2017
Troxyca ER(Pfizer)
Not Launched
RoxyBond (Inspirion/Daiichi
Sankyo) Not Launched
ARYMO ER (Egalet)
2017 Launch
Apadaz (KemPharm )Not Launched
FDA-approved ADF opioid formulations and technologies launched in the US
Source: Pharmaprojects®, September 2018
Pain treatment remains a prolific research area, with smaller specialty and mid-sized drug companies exceeding activity from big pharma companies.
This dynamic is the same as it related to industry-sponsored trials of opioids and trials of ADFs.
Industry sponsors invested in clinical development of pain therapies
Sour
ce: T
rialtr
ove®
, Oct
ober
201
8
126IndustryGeneric
504Industrytop 20
Pharma
Industryall otherPharma
504
All Opioid Trials
10IndustryGeneric
36Industrytop 20
Pharma
Industryall otherPharma
167
ADF Trials
Top sponsors of all clinical trials with pipeline and approved ADF opioids
Num
ber o
f tria
ls
0
5
10
15
20
25 Completed
Terminated
Closed
Temporarily Closed
Open
Purdue
Pfize
rAcu
raEg
aletElite
KemPharm
Collegium
Pain Th
erapeutics
Endo
Relmada
Intellip
harmace
uticals
Johnso
n & Jo
hnson
Gruenthal
Nektar
Mundipharma
Durect
Ensysc
e
Insp
iratio
n
QRxPharm
aTe
va
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ce: T
rialtr
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ober
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Pfizer and Purdue tied as the leading sponsors in clinical development of ADFs – most of their trials have been completed and led to successful launches of several ADFs currently on market.
Egalet, KemPharm, Sun Pharma, and Teva share the lead for currently active trials in this space.
What’s coming up in the pipeline for ADFs?
Phase I Phase II Phase III
Number of Trials
0 2 4 6 8 10
hydromorphone (Flamel)
hydrocodone bitartrate ER (Zogenix)
acetaminophen/hydrocodone bitartrate (Grunenthal)
acetaminophen/hydrocodone bitartrate (Teva)
hydromorphone ER prodrug (Signature)
hydromorphone ER prodrug (KemPharm)
oxycodone CR (Elite)
morphine/oxycodone (MoxDuo CR)
levorphanol, TheraQuest
SDN-021
ELI-202
oxycodone/naltrexone (Elite)
Rexista (oral)
tapentadol TRF
oxycodone/naltrexone (once daily), Elite
acetaminophen/hydrocodone (Acura)
oxycodone CR (Egalet)
Hydrocodone bitartrate (Vantrela)
Oxycodone (Remoxy)
Oxycodone/niacin (Acura)
Most trials of pipeline ADFs are in Phase I or III, and there is little presence of Phase II trials.
This accelerated advancement is likely due to the fact that ADFs are largely reformulations of approved or generic opioids.
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ce: T
rialtr
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Strategies of non-opioid drug development
There are many non-opioid medications available over the counter and by prescription.
But, while people do pursue these pain strategies to avoid the opioid-related addictive and abusepotential, non-opioids are not always effectiveand may induce additional side effects.
Development for Pain
28 662Phase I
79Phase II Phase III Pre-
registration
Source: Pharmaprojects®, October 2018
175 non-opioid drugs are currently in development for nociceptive or neuropathic pain
28259777665443322222
Mechanisms of action (MOA) of non-opioid drugs in development (>2 drugs/MoA)Sodium channel antagonist
Cyclooxygenase inhibitorCannabinoid receptor agonist
Alpha 2 adrenoreceptor agonist
Calcium channel antagonist
Potassium channel antagonistProstaglandin synthase inhibitor
Vanilloid receptor 1 agonistVanilloid receptor 1 antagonistAcetylcholine release inhibitor
Nerve growth factor antagonistStem Cell Therapy
Glucocorticoid agonistAminopeptidase microsomal inhibitor
Hyaluronic acid stimulant
Membrane metallo endopeptidase inhibitor
Source: Pharmaprojects®, October 2018
Despite hurdles from payers and the continuing challenge to find the appropriate balance between patient access and rising abuse, the journey to battle the opioid epidemic continues.
NMDA receptor antagonistTrkA tyrosine kinase inhibitor
Sodium channel antagonists28 drugs
Cyclooxygenase inhibitors25 drugs
The top mechanisms with the most drugs in development are:
MorphaBond ER (Inspirion/Daiichi
Sankyo ) 2017 Launch
