Depression Rising (Again): Turning the Corner in Psychiatry's Most Burdensome Disorder - Real Endpoints
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Depression Rising (Again): Turning the Corner in Psychiatry’s Most Burdensome Disorder Joel Sandler, Ph.D. Associate Principal, Defined Health Harry Tracy, Ph.D. Founder and President, NI Research Roger Longman Chief Executive Officer, Real Endpoints Defined Health Insight Series Briefing June 18, 2018
SSRIs: The Rise and Fall (i.e. Genericization) of an Empire EvaluatePharma Insight Series Briefing – Turning the Corner in Depression © Defined Health, 2018 2
And Yet the Problem Intensifies
Suicide rates have been rising in nearly every state, according to the latest Vital Signs report by the Centers for
Disease Control and Prevention (CDC). In 2016, nearly 45,000 Americans age 10 or older died by suicide. Suicide is
the 10th leading cause of death and is one of just three leading causes that are on the rise.
CDC.gov
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 3
Partnering Activity Remains Tepid at Best
12/09: AZ granted exclusive 4/10: BMS granted rights to
rights to Targacept’s TC-5214 NeurOp's small molecule
Partnering Deal Activity (2009-17)
1/17: Janssen partnered
($200M upfront) NMDA library ($1.5M upfront) 12/12: Janssen granted rights to with Amorsa to develop
2/15: Lilly granted
10 Evotec's portfolio of oral small Cerecor rights to therapies for TRD (ketamine 2000
molecule NMDA antagonists
Deal Value ($M)
6/11: Sumitomo granted CERC-501 (a KORA) analogs)
8 1500
No. Deals
rights to Neuralstem’s NSI-
6 189 (neurogenesis) in Japan 4/13: Merck granted
Cerecor rights to 1000
4
CERC-301 (NMDA) 500
2
0 0
2009 2010 2011 2012 2013 2014 2015 2016 2017
Reuptake inhibitor 5 2 4 1 1
Atypical antipsychotic 1 1 3 1
NMDA 1 1 1 1 1 1
Molecular segmentation 2 1 1 1
Undisclosed MOA 1 1
Device 1
Gene therapy 1
Assets
MAOI 1
Muscarinic receptor 1
Neurokinin 1 inhibitor 1
Nicotinic receptor 1
Nootropic 1
Opioid receptor 1
Opioid receptor 1
Other antipsychotic 1
Patient monitoring 1
BCIQ
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 4
NMDA Modulators Well-Represented in Late-Stage Pipeline
Phase 2-Registration Depression US Depression Clinical Development
Pipeline by Target Pipeline by Phase
(n = 40) (n = 76)
NMDA receptor 4
Opioid kappa/mu 9 7
Preclinical
receptor
AChR 13 29 Phase 1
GABAA-R
Phase 2
Triple reuptake
inhibitor 4 Phase 3
5-HT2A
29
Prereg.
Other (n=1 ea.*) 2 3
3 7
3
Adis, Cortellis
*n-of-1 targets include: SSRI + 5-HT1A, 5-HT1A, 5-HT7, D2/D3 receptor, D2/D3 + 5-HT1A/2A, IL-6, mGluR5, NET, Neuronal growth factor receptor, Chemosensory receptors, NOPR, Orexin-2, SSRI
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 5
The New Crop of Antidepressants?
Emerging Allergan Sage Therapeutics Marinus Janssen
Programs Rapastinel Brexanolone SAGE-217 Ganaxolone Esketamine
Dev. Phase 3 Pre-reg 2 2 3
Exp. Entry Date 2020 2018/2019 2020 2021 2019
Indication(s) TRD PPD MDD, PPD PPD TRD
GABA A receptor GABA A receptor GABA A receptor NMDA receptor
MOA NMDA partial agonist
modulator modulator modulator antagonist
ROA IV IV Oral IV, Oral Intranasal
Rapid effect; pivotal Rapid effect; valuation Rapid effect; expedited Top-line PPD data for IV Marginal but significant
Comments data due 1H2019; oral largely based on next- development plan and oral formulations improvement vs.
program in-licensed gen oral analog (‘217) announced by FDA expected later this year placebo
Adis, Cortellis, company press releases
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 6
Succession (and Modest Diversification) on the Horizon
SNRIs (LLY’s US Sales by Product MOA Bullish
Cymbalta, PFE’s projections Unclassified
5500 Protracted uptake
Pristiq) dominated for Sage’s
Takeda’s of JNJ’s esketamine DRI/NRI/NDMA receptor antagonist
5000 from 2009-2013 GABA-A
Trintellix followed by modulators Kappa/Mu opioid receptor antagonist
projected to Allergan’s
4500
achieve rapastinel NMDA receptor antagonist
4000 short-lived
success GABA-A regulator
US Sales ($M)
3500 Along with schizophrenia, Histamine H1; 5-HT2A
Otsuka’s Rexulti approved
3000 Dopamine D2; 5-HT1A/2
as adjunct in TRD
2500 Generic SSRIs had 5-HT1A agonist;SSRI
entered market in 5-HT1A/1B/3/7; SERT
2000
early 2000s
1500
MAO-I
DRI/NRI
1000
SNRI
500
SSRI
0
2009 2011 2013 2015 2017 2019 2021 2023
EvaluatePharma
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 7
Rollercoaster Rides – Sage’s Valuation Largely Driven by Performance of Oral ‘217
SAGE Therapeutics, Inc. (SAGE:NASDAQ) Market Summary
November 2017: brexanolone
demonstrated rapid and long-lasting
reduction in depressive symptoms
over 30 days in two Ph3 trials in
moderate-severe PPD
December 2017: 64% of SAGE-
217 patients achieved MDD
remission at day 15 of
September 2017: treatment vs. 23% of placebo June 2018: FDA to accept
brexanolone missed single 450 patient MDD
primary endpoint in SRSE trial to support marketing
approval of SAGE-217;
ongoing PPD trial now be
considered a pivotal
Yahoo Finance, company press releases
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 8
Rollercoaster Rides – FDA Now Willing to Review Alkermes’ Opioid Receptor Modulator Insight Series Briefing – Turning the Corner in Depression © Defined Health, 2018 9
Towards a Tipping Point in Depression?
Will regulatory and “The risk associated with CNS drug
commercial success development broadly is considered
catalyze further too great as commercial risk is
added to the inherent scientific
enthusiasm, investment?
and clinical development risk
associated with neuropsychiatric
disease.”
- GS Johnson, Neurobiol Dis. 2014
Are emerging clinical Remaining gaps,
candidates adequately opportunities for
positioned to address innovators, partners,
unmet needs? investors?
Insight Series Briefing – Turning the Corner in Depression
© Defined Health, 2018 10As a class, 2018 neuro drugs will face not insignificant access
challenges
Average of 114.3 calculated from all 2018 launches/likely launches scored
realendpoints.com | 12Brexanolone from a payer’s point of view
Access Advantages Access Challenges
• Treats high unmet need • New payer-expense
• Limited therapy duration category
• FDA breakthrough status • Undefined volume of use
• Medical benefit drug • Off-label potential: label and
evidence uncertainty re.
• Effective patient advocacy
moderate PPD
organizations in category
• Durability of effect given
30-day endpoint
realendpoints.com | 13Samidorphan/buprenorphine from a payer’s point of view
Access Advantages Access Challenges
• Protected class • Many generic ”step-
• Novel mechanism throughs”
• Serious disease • Mixed trial results
• Superiority data vs • Limited bundling advantage
competitive agents vs competitors
• If pricing high, patient cost-
sharing challenges in
Medicare
realendpoints.com | 14You can also read
