Full Press Release Details
Forward Looking Statements
contains forward-looking statements, including, but not limited to, statements related to future financial results, potential proceeds under the Grunenthal agreement, the process and timing of anticipated future development of AcelRx s product
candidates, including Zalviso, the NDA submission and the CRL, the recent meeting held with the FDA to discuss the CRL, AcelRx s plans to address the issues raised in the CRL, and anticipated resubmission of the Zalviso NDA to the FDA,
including the scope of the resubmission and the timing of the resubmission and FDA review time, the impact, if any, of the FDA s review of the amendments to the Zalviso NDA that were not previously reviewed, planned initiation of the Phase 3
clinical trial for ARX-04, and the therapeutic and commercial potential of AcelRx Pharmaceuticals product candidates, including Zalviso. These forward-looking statements are based on AcelRx Pharmaceuticals current expectations and
inherently involve significant risks and uncertainties. AcelRx Pharmaceuticals actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and
uncertainties, which include, without limitation, risks related to: AcelRx Pharmaceuticals ability to receive regulatory approval for Zalviso; any delays or inability to obtain and maintain regulatory approval of its product candidates,
including Zalviso, in the United States and Europe; AcelRx s ability to build an effective commercial organization; its ability to receive any milestones or royalty payments under the Grunenthal agreement; its ability to obtain sufficient
financing to commercialize Zalviso and proceed with clinical development of ARX-04; the success, cost and timing of all product development activities and clinical trials, including the planned Phase 3 ARX-04 trial; the market potential for its
product candidates; the accuracy of AcelRx s estimates regarding expenses, capital requirements and needs for financing; and other risks detailed in the Risk Factors and elsewhere in AcelRx Pharmaceuticals U.S. Securities and
Exchange Commission filings and reports, including its Quarterly Report on Form 10-Q filed with the SEC on November 10, 2014. AcelRx Pharmaceuticals undertakes no duty or obligation to update any forward-looking statements contained in this
release as a result of new information, future events or changes in its expectations.
AcelRx Working to Improve Acute Pain Management
ZalvisoTM profile from Phase 3 studies
Demonstrated in two placebo controlled studies, 1 active comparator study Adverse events: Most common related AE s were nausea, vomiting, O2 desaturation, itching High patient satisfaction and nurse ease of care reported
Gr nenthal partnership to commercialize Zalviso in EU & Australia established
Terms: $250M upfront and potential milestones, mid-teens to mid-twenties % royalty Other Territories: Continue to seek
additional partnerships in Asia & South America CE Mark: Received December 2014 MAA filed in Switzerland
Upcoming regulatory catalysts in US and EU
NDA resubmission targeted Q1 2015 EU: Day 120 submission planned for Q1 2015
Strong balance sheet with $75
million cash on hand December 31, 2014 (unaudited) 3
Zalviso NDA Status-CRL received July 25, 2014
Demonstration of a reduction in the incidence of optical system errors
Optical system errors were noted in the clinical setting at a single digit rate Did not appear to impact Phase 3 safety and efficacy results Improvements have been made to reduce error
rate Additional bench testing to be completed to confirm error rate reduction
Changes to the Instructions for
Use (IFU) to address inadvertent dosing
15 misplaced tablets of ~30,000 doses IFU modified to address this
HF studies will be required to confirm IFU/GUI changes are adequate
Support for shelf life (not approvability issue)
Data to be provided to support 24 month dating
Zalviso NDA Resubmission Plan
FDA to clarify CRL issues held
Modifications to dispenser completed IFU modifications completed
Protocols for bench testing and HF study submitted to FDA
Shelf life data available and to be included in resubmission FDA to review and comment on protocols
Bench testing and HF work to be completed Expected to refile by end of Q1 2015
Type II submission (6 month review)
Proposed Indication: Management of
Severe In-Hospital Acute Pain
Investigational drug and delivery system not FDA approved for commercial use
IV PCA Current Standard of Care
In-hospital, post-operative moderate to severe pain control Higher Patient satisfaction when patients control their own
Invasive route of delivery
IV infiltration causes analgesic gaps IV connection restricts patient mobility Risk of IV site infection
Infusion pumps large source of
morbidity / mortality1 1/9 harmful hospital errors due to IV PCA2
1. FDA / AAMI Summit Meeting held October
2. Calculated from The rate and
costs attributable to intravenous patient-controlled analgesia errors. Brian Meissner et al, Hospital Pharmacy April 2009
Zalviso: Leveraging Sufentanil
Enables rapid transmucosal
uptake 6 minute brain:plasma equilibration
No active metabolites
1. Mather, Clin Exp Pharmacol Physiol 1995; 22:833.
2. Kumar, Eur J Pharmacol 2008; 597:39 (ED50) and Purdue Pharma MSDS, 2009 (LD50)
Sublingual Sufentanil Delivery
May reduce IV peaks & troughs
may minimize swallowed drug May result in high bioavailability Helps with goal of consistent dose delivery
Supplied in cartridge of 40 Tablets
2 days for average patient
Zalviso: Delivery Device Design and Feature Set
Non-invasive (sublingual) delivery
Eliminates IV infection risk May enhance ambulation
Pre-programmed delivery
Factory set 20-minute lockout period Addresses end-user programming error risk
Design safety features
cartridge provides full inventory loop tracking of sufentanil tablets RFID thumb tag co-located to device helps reduce proxy dosing HCP controlled access, device tether reduces risk of product loss Battery power ensures 72-hour function even in the
event of power outage
Investigational drug and delivery system not FDA approved for commercial use
Zalviso Phase 3 Program
Surgery Type Study Type Sites N Data
Open-label, Zalviso non-inferior to IV
Abdominal & (p<0.001)
Active-comparator 359 Nov
Patient Global 26 Zalviso also demonstrates
Surgery (IAP309) Assessment of Method of superiority to IV PCA
Pain Control over 48 hrs (p=0.007)
Double-blind, Sufentanil treatment
Placebo-controlled 178 Mar
13 superior to placebo
Surgery (IAP310) 1o EP:Sum of Pain Intensity 2:1 2013
Difference over 48 hrs p=0.001
Double-blind, Sufentanil treatment
Placebo-controlled 426 May
34 superior to placebo
Surgery (IAP311) 1o EP:Sum of Pain Intensity 3:1 2013
Difference over 48 hrs p<0.001
IAP310 & IAP311 Primary Endpoint:
SPID-48 ITT Population
120 100 80 60 40 20 0
0.25 0.75 2 6 10 16 24 32 40 48
Sufentanil NanoTab Placebo
Time afterTime first (hrs) study drug dosing
Sufentanil NanoTab Placebo
100 80 60 40 20 0 -20
0.25 0.75 2 6 10 16 24 32 40 48
Zalviso: Studies Indicate Ability to Control Moderate to Severe Acute Pain