Enanta Pharmaceuticals Announces 96 Percent SVR12 in Treatment Experienced Genotype 1 Hepatitis C Patients in SAPPHIRE-II Study

  Enanta Pharmaceuticals Announces 96 Percent SVR12 in Treatment Experienced
  Genotype 1 Hepatitis C Patients in SAPPHIRE-II Study

- Second of Six All-Oral, Interferon-Free Phase 3 Hepatitis C Studies Using
Regimen Containing ABT-450

Business Wire

WATERTOWN, Mass. -- December 10, 2013

Enanta Pharmaceuticals, Inc. (NASDAQ:ENTA) today announced results from the
SAPPHIRE-II study, the second of six phase 3 registrational studies being
conducted by AbbVie for the treatment of hepatitis C virus (HCV) genotype 1
(GT1) infection, using a regimen containing Enanta’s lead protease inhibitor
ABT-450. ABT-450 is part of AbbVie’s investigational three direct-acting
antiviral (3D) regimen, consisting of boosted protease inhibitor
ABT-450/ritonavir, NS5A inhibitor ABT-267, and non-nucleoside polymerase
inhibitor ABT-333. The SAPPHIRE-II study used this 3D regimen plus ribavirin.

Results from the 394-patient SAPPHIRE-II trial demonstrated a sustained
virologic response at 12 weeks post-treatment (SVR[12]) of 96 percent in
chronically infected GT1 HCV treatment experienced adult patients who had
previously failed pegylated interferon and ribavirin treatment. Approximately
49 percent of these patients were prior null responders, namely patients
defined as not achieving a significant reduction in the HCV virus during their
prior treatment. The majority of patients were GT1a, considered the more
difficult-to-treat subtype, and the SVR[12] rates of GT1a and GT1b were 96
percent and 97 percent, respectively. These results were based on an
intent-to-treat analysis and were achieved after 12 weeks of treatment.
Virologic relapse or breakthrough was noted in 2 percent of patients receiving
the 3D regimen plus ribavirin. The treatment regimen was well tolerated, with
1 percent of patients discontinuing treatment due to adverse events.

“The high SVR rates in this SAPPHIRE-II trial and the previously reported
SAPPHIRE-I trial further validate this 3D regimen plus ribavirin for both
treatment-naive and treatment-experienced patients,” stated Jay R. Luly,
Ph.D., President and Chief Executive Officer. “We look forward to the
remaining phase 3 studies reading out using the same 3D regimen with and
without ribavirin, as well as in the treatment of HCV patients with
cirrhosis.”

About Study M13-098 (SAPPHIRE-II)

Following SAPPHIRE-I, SAPPHIRE-II is the second placebo-controlled trial and
the second of six phase 3 trials supporting AbbVie’s investigational 3D
regimen for the treatment of GT1 hepatitis C patients. AbbVie will disclose
detailed SAPPHIRE-II results at future scientific congresses and in
publications.

SAPPHIRE-II is a global, multi-center, randomized, double-blind,
placebo-controlled study to evaluate the efficacy and safety of 12 weeks of
treatment with ABT-333 (250mg), ribavirin (weight-based), both dosed twice
daily, and the fixed-dose, co-formulated combination of ABT-450/ritonavir
(150/100mg) and ABT-267 (25mg) dosed once daily in non-cirrhotic, GT1a and
GT1b HCV-infected, treatment-experienced adult patients who previously failed
treatment with pegylated interferon and ribavirin.

The study population consisted of 394 GT1 treatment-experienced patients with
no evidence of liver cirrhosis. 297 patients were randomized to the 3D regimen
plus ribavirin for 12 weeks, and 97 patients were randomized to placebo for
the initial 12 weeks. Patients initially randomized to placebo for the first
12 weeks then received open-label treatment with the 3D regimen plus ribavirin
for 12 weeks. In the study, 49 percent of patients were prior null responders
to pegylated interferon and ribavirin, generally considered among the most
difficult to treat successfully.

Following 12 weeks of treatment with AbbVie’s 3D regimen plus ribavirin, 96
percent (n=286/297) of patients achieved SVR[12] based on an intent-to-treat
analysis, where patients with missing values for any reason were considered
treatment failures. The SVR[12] rates in GT1a and GT1b patients were 96
percent (166/173) and 97 percent (119/123), respectively. One subject had HCV
genotype 1 and achieved SVR[12], but was unable to be sub-genotyped.

The most commonly reported adverse events in both the 3D and placebo arms were
headache, fatigue and nausea. Discontinuations due to adverse events were
reported in three (1 percent) patients receiving the 3D regimen and no
patients receiving placebo. Virologic relapse or breakthrough was noted in 2
percent of patients receiving the 3D regimen plus ribavirin.

AbbVie has announced that results from the remaining four ABT-450 containing
studies in AbbVie’s phase 3 program will be available in the coming months.

Overview of AbbVie’s phase 3 clinical programs:

                                                                 
Study          Patients (N)            Treatment           Treatment 
                                           Regimen                 Duration
                                             *ABT-450/r^b
                                           +ABT 267^c      12 weeks  
                                             *ABT-333
                                             *Ribavirin
SAPPHIRE-I       GT1, treatment-naïve                              12 weeks,
                 (631)                                             then
                                         *Placebo         active    
                                                                   treatment
                                                                   for 12
                                                                   weeks
                                             *ABT-450/r
                                             +ABT-267        12 weeks  
                                             *ABT-333
                 GT1,                        *Ribavirin
SAPPHIRE-II      treatment-experienced                             12 weeks,
                 (394)                                             then
                                         *Placebo         active    
                                                                   treatment
                                                                   for 12
                                                                   weeks
                                             *ABT-450/r
                                             +ABT-267        12 weeks  
                 GT1b,                       *ABT-333
PEARL-II         treatment-experienced       *Ribavirin
                 (210 ^ a)                   *ABT-450/r
                                           +ABT-267        12 weeks  
                                             *ABT-333
                                             *ABT-450/r
                                             +ABT-267        12 weeks  
                                             *ABT-333
PEARL-III        GT1b, treatment-naïve       *Ribavirin
                 (400 ^ a)                   *ABT-450/r
                                           +ABT-267        12 weeks  
                                             *ABT-333
                                             *Placebo
                                             *ABT-450/r
                                             +ABT-267        12 weeks  
                                             *ABT-333
PEARL-IV         GT1a, treatment-naïve       *Ribavirin
                 (300 ^ a)                   *ABT-450/r
                                           +ABT-267        12 weeks  
                                             *ABT-333
                                             *Placebo
                                             *ABT-450/r
                 GT1, treatment-naïve        +ABT-267        12 weeks  
                 and                         *ABT-333
TURQUOISE-II     treatment-experienced       *Ribavirin
                 (with compensated           *ABT-450/r
               cirrhosis)                  +ABT-267        24 weeks  
                 (380 ^ a)                   *ABT-333
                                             *Ribavirin
                                                            

^a projected study population
^b ABT-450/ritonavir
^cABT-267 is co-formulated with ABT-450/r, administered as two pills once
daily

Additional information about AbbVie’s phase 3 studies can be found at
www.clinicaltrials.gov.

Protease Inhibitor Collaboration with AbbVie (formerly the research-based
pharmaceutical business of Abbott Laboratories)

In December 2006, Enanta and Abbott announced a worldwide agreement to
collaborate on the discovery, development and commercialization of HCV NS3 and
NS3/4A protease inhibitors and HCV protease inhibitor-containing drug
combinations. ABT-450 is a protease inhibitor identified as a lead compound
through the collaboration. Under the agreement, AbbVie is responsible for all
development and commercialization activities for ABT-450. Enanta received $57
million in connection with signing the collaboration agreement, has received
$55 million in subsequent clinical milestone payments, and is eligible to
receive an additional $195 million in payments for regulatory milestones, as
well as double-digit royalties worldwide on any revenue allocable to the
collaboration’s protease inhibitors. Also, for any additional collaborative
HCV protease inhibitor product candidate developed under the agreement, Enanta
holds an option to modify the U.S. portion of it rights to receive milestone
payments and worldwide royalties. With this option,Enanta can fund 40 percent
of U.S. developmentcosts and U.S. commercialization efforts(sales and
promotion costs) for the additional protease inhibitor inexchange for 40
percent of any U.S. profits ultimately achieved afterregulatory approval,
instead ofreceiving payments for U.S. commercialregulatory approval
milestones and royalties on U.S. sales of that protease inhibitor.

About Hepatitis C Virus (HCV)

Hepatitis C is a liver disease affecting over 170 million people worldwide.
The virus is typically spread through direct contact with the blood of an
infected person. Hepatitis C increases a person’s risk of developing chronic
liver disease, cirrhosis, liver cancer and death. There is an acute need for
new HCV therapies that are safer and more effective for many variants of the
virus.

About Enanta

Enanta Pharmaceuticals is a research and development-focused biotechnology
company that uses its robust chemistry-driven approach and drug discovery
capabilities to create small molecule drugs in the infectious disease field.
Enanta is discovering, and in some cases developing, novel inhibitors designed
for use against the hepatitis C virus (HCV). These inhibitors include members
of the direct acting antiviral (DAA) inhibitor classes – protease (partnered
with AbbVie), NS5A (partnered with Novartis) and nucleotide polymerase – as
well as a host-targeted antiviral (HTA) inhibitor class targeted against
cyclophilin. Additionally, Enanta has created a new class of antibiotics,
called Bicyclolides, for the treatment of multi-drug resistant bacteria, with
a focus on developing an intravenous and oral treatment for hospital and
community MRSA (methicillin-resistant Staphylococcus aureus) infections.

Forward Looking Statements Disclaimer

This press release contains forward-looking statements, including with respect
to clinical data, plans for announcing additional data, and the planned
clinical development and regulatory submissions for ABT-450. Statements that
are not historical facts are based on our management’s current expectations,
estimates, forecasts and projections about our business and the industry in
which we operate and our management’s beliefs and assumptions. The statements
contained in this release are not guarantees of future performance and involve
certain risks, uncertainties and assumptions, which are difficult to predict.
Therefore, actual outcomes and results may differ materially from what is
expressed in such forward-looking statements. Important factors that may
affect actual results include final results of ongoing clinical trials, the
development and marketing efforts of AbbVie (our collaborator on ABT-450),
regulatory actions affecting clinical development of ABT-450 and clinical
development of competitive product candidates. Enanta cautions investors not
to place undue reliance on the forward-looking statements contained in this
release. These statements speak only as of the date of this release, and
Enanta undertakes no obligation to update or revise these statements, except
as may be required by law.

Contact:

Investor Contact
Carol Miceli, 617-607-0710
cmiceli@enanta.com
or
Media Contact
MacDougall Biomedical Communications
Kari Watson, 781-235-3060
kwatson@macbiocom.com
 
Press spacebar to pause and continue. Press esc to stop.