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DURECT Corporation Announces Preliminary Data from the Ongoing DUR-928 Alcoholic Hepatitis Phase 2a Trial

Live  Webcast of AH Data Presentation and Discussions by KOLs Steven Flamm, M.D., Tarek  I. Hassanein, M.D. and Paul Kwo, M.D. Tomorrow, Wednesday, May 8, 2019 at 8:30  a.m. ET

CUPERTINO, Calif., May 7, 2019 /PRNewswire/ -- DURECT Corporation  (Nasdaq: DRRX) today announced preliminary data from the ongoing DUR-928  alcoholic hepatitis (AH) Phase 2a clinical trial.  On Wednesday, May 8th at 8:30 a.m.  Eastern Time, DURECT will host a Key Opinion Leader (KOL) and earnings conference  call, during which the Company will discuss financial results for the first  quarter of 2019, provide a corporate business update, and present preliminary  AH clinical trial data via webcast. Also participating in the call will be  three KOLs on alcoholic hepatitis: Drs. Steven Flamm, Tarek Hassanein, and Paul  Kwo.  Dr. Kwo will present an overview of  AH including details on the disease and its progression, current treatment  options and new treatments in development. Drs. Hassanein and Flamm will  discuss their experience treating patients in the ongoing DUR-928 AH clinical  trial.

Preliminary Results

Ten  patients have completed dosing with DUR-928 to date in the ongoing open label,  dose-escalation, multi-center U.S. trial. Eight patients (4 moderate and 4  severe) have been treated with DUR-98 at the 30 mg dose, and two patients (1  moderate and 1 severe) at the 90 mg dose.

Lille  scores are used in clinical practice to help determine the prognosis for AH  patients after 7 days of treatment. Patients with a Lille score below 0.45 have  an 85% 6-month survival rate vs. those with Lille scores of above 0.45, have only  a 25% 6-month survival rate (Louvet A et  al. Hepatology 2007; 45: 1348-54). The lower the Lille score, the better  the prognosis is for the AH patient. In our study, the median Lille score for  the 9 AH patients treated with DUR-928 who returned for their Day 7 visit is  0.04, with a range of 0.01 to 0.19. The median Lille score among a cohort of 15  patients treated with either supportive care or supportive care with  corticosteroids at the University of Louisville (UL) is 0.41 (shown  as historical control). 1

The chart below shows  individual patient Lille scores plotted as a function of their initial MELD  scores.

     
  1. Our advisor, Dr. Craig McClain from the University of  Louisville (UL), shared anonymized data from his study, in which 15 AH patients  with initial MELD scores ranging from 15-30 received either supportive care  alone (n=8) or supportive care with corticosteroids (n=7).
  2.  
  3. Of the 10 AH patients dosed to date with DUR-928, one patient  did not return for the day 7 visit, so Lille scores could only be calculated  for 9 of 10 patients.
  4.  
  5. Lille scores in the DUR-928 patients were significantly  lower than that of the UL patients (p=0.002; Wilcoxon's Rank Sum Test).

Mathurin et al. proposed three  prognostic classifications of AH patients in response to treatment based on  Lille scores and their correlation with 28-day survival rates from a  meta-analysis of four randomized controlled trials evaluating the effectiveness  of corticosteroids in an aggregate of 324 patients with severe AH. (Methurin P. et al. Gut 2011; 60:255-260)  The following table shows the percentage of patients from three AH data sets,  including DUR-928, in each Mathurin classification based on patients’ Lille  scores. Seventy-eight percent (7/9) of the DUR-928 treated AH patients with  Lille scores are classified as complete responders, 22% (2/9) are partial  responders and none (0/9) were null responders. 

     
  1. Mathurin, et. al., Gut 2011;60:255-260
  2.  
  3. Mathurin, “Selonsertib in Combination with Prednisolone  for the Treatment of Severe Alcoholic Hepatitis:  A Phase 2 Randomized Controlled Trial” presented  at AASLD San Francisco November 2018. The table presents patients from the control  group – all treated with corticosteroids (prednisolone + placebo).  Initial MELD scores in this study ranged from  19 to 24.
  4.  
  5. See footnote 1 on page 1.   d) See footnote 2 on page 1.   e) See footnote 3 on page 1.

Bilirubin is formed by  the breakdown of red blood cells in the body. The level of total bilirubin in  the blood is an indication of how the liver is functioning.  Compared to baseline (n=10), the median  reduction in total bilirubin in the DUR-928 treated patients was 16% at Day 7 (n=9)  and 41% at Day 28 (n=8) compared to 3% at Day 7 and 35% at Day 28 in the UL  patients.  The chart below shows the  percent change in total bilirubin at Day 7 and 28 compared to baseline (Day 0)  for both the separate UL (as historical control) and DUR-928 studies. 

                                P-Values  calculated with Wilcoxon's Signed Rank Test

Model  of End-Stage Liver Disease (MELD) score is another common scoring system used to  assess the severity and prognosis of AH patients. Patients with MELD scores of  11-19 are classified as having moderate AH and patients with MELD scores of  20-30 are classified as having severe AH.   As with Lille scores, the lower the MELD score, the better the prognosis  for the AH patient.  In our study (shown  in the chart below), the median reduction from baseline (Day 0, prior to  treatment) (n=10) in MELD in the DUR-928 treated patients was 4% at Day 7 (n=9)  and 21% at Day 28 (n=8) compared to a 4% increase at Day 7 and 6% reduction at  Day 28 in the UL patients (as historical control).

MELD is calculated based on (a) bilirubin, (b) serum  creatinine (sCr), and (c) International Normalized Ratio (INR), which is a  measure of prothrombin time.    P-Values  calculated with Wilcoxon's Signed Rank Test

To date there is no  statistical difference in the pharmacokinetic profiles between moderate and  severe AH patients treated with DUR-928. There have been no drug-related  adverse events in the DUR-928 treated patients to date.

The data presented in  this press release are preliminary and will be finalized upon completion of the  trial. There can be no assurance that additional patients treated with DUR-928  will have similar results as those reported here.

About the Ongoing DUR-928 Alcoholic Hepatitis Phase 2a  Trial

DURECT is conducting a  Phase 2a clinical trial with intravenously administered DUR-928 in patients  with AH.  This is an open label, dose  escalation (30, 90 and 150 mg), multi-center U.S. study that is enrolling  patients with moderate and severe AH.   Dose escalation may occur following review of safety and pharmacokinetic  (PK) results of the prior dose level by a Dose Escalation Committee (DEC). The  target number of patients for the study is 4 moderate and 4 severe patients per  dose group. The objectives include assessment of safety, PK and pharmacodynamic  (PD) signals, including liver chemistry and biomarkers.

Conference  Call and Webcast with Slides

Wednesday,  May 8th at 8:30 a.m. Eastern Time/5:30 a.m. Pacific Time

Toll  Free:                     888-882-4478

International:                323-794-2590

Conference  ID:             7156796

Webcast:                      http://public.viavid.com/index.php?id=134476

A  live audio webcast and data slide presentation will be available by accessing  DURECT's homepage at www.durect.com and clicking  "Investors." If you are unable to participate during the live  webcast, the call and slide presentation will be archived on DURECT's website  under “Event Calendar – Past Events” in the "Investors" section.

About DURECT Corporation

DURECT  is a biopharmaceutical company actively developing therapeutics based on its  Epigenetic Regulator Program and proprietary drug delivery platforms.  DUR‑928, a new chemical entity in Phase 2  development, is the lead candidate in DURECT’s Epigenetic Regulator  Program.  An endogenous, orally  bioavailable small molecule, DUR-928 has been shown in preclinical studies to play  an important regulatory role in lipid homeostasis, inflammation, and cell  survival.  Human applications may include  acute organ injury such as AH and acute kidney injury (AKI), chronic hepatic  diseases such as nonalcoholic steatohepatitis (NASH), and inflammatory skin  conditions such as psoriasis and atopic dermatitis.  DURECT’s advanced oral and injectable  delivery technologies are designed to enable new indications and enhanced  attributes for small-molecule and biologic drugs.  Late stage product candidates in this  category include POSIMIR® (bupivacaine extended-release solution),  an investigational locally-acting, non-opioid analgesic intended to provide up  to 3 days of continuous pain relief after surgery, and ORADUR®-Methylphenidate  ER Capsules, approved in Taiwan as Methydur Sustained Release Capsules, where  it is indicated for the treatment of attention deficit hyperactivity disorder  (ADHD).  In addition, for the assignment  of certain patent rights, DURECT receives single digit sales-based earn-out  payments from U.S. net sales of Indivior’s PERSERIS (risperidone)  drug for schizophrenia, which was commercially launched in February 2019.  For more information, please visit www.durect.com.

DURECT Forward-Looking Statement

The statements in this press release  regarding preliminary data from the ongoing Phase 2a trial of DUR-928 in  patients with AH, including data regarding Lille scores, response rates and  bilirubin and MELD reductions are forward looking statements to the extent that  they suggest that they are predictive of results for the full trial or for the  outcomes of the patients whose data is reported.  This press release also includes additional  forward looking statements, including regarding clinical trial plans for DUR-928,  the potential use of DUR-928 to treat AH, AKI, chronic hepatic diseases such as  NASH, and inflammatory skin disorders such as psoriasis and atopic dermatitis,  as well as statements regarding the use of POSIMIR to treat post-surgical pain,  the use of Methydur to treat ADHD, and potential earn-out payments from U.S.  sales of PERSERIS.  These forward-looking  statements involve risks and uncertainties that can cause actual results to  differ materially from those in such forward-looking statements. Potential  risks and uncertainties include, but are not limited to, that the remainder of  the Phase 2a clinical trial of DUR-928 in AH patients does not replicate the  interim results reported here, the risk of delays in the enrollment of the  ongoing clinical trials of DUR-928 in AH, NASH and psoriasis, potential adverse  effects arising from the testing or use of DUR-928, the risk that the FDA may  not approve the POSIMIR NDA, the risk that PERSERIS and Methydur will not have  successful launches, our ability to avoid infringing patents held by other  parties and secure and defend patents of our own patents, and our ability to  manage and obtain capital to fund our operations and expenses. Further  information regarding these and other risks is included in DURECT's Form 10-Q filed  with the Securities and Exchange Commission on May 7, 2019 under the heading  "Risk Factors."

CONTACT: Michael H. Arenberg, Chief  Financial Officer, DURECT 408-346-1052