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

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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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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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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