Adherex Announces Results From Two Sodium Thiosulfate Phase 3
Studies Presented at the 50th American Society of Clinical Oncology
(ASCO) Meeting
-COG STUDY ACCL0431 meets primary endpoint for prevention of
cisplatin-induced hearing loss in children
-SIOPEL 6 Data Monitoring Committee recommends continuation of
study after safety review of 80 standard risk hepatoblastoma
patients
RESEARCH TRIANGLE PARK, NORTH CAROLINA--(Marketwired - Jun 2,
2014) - Adherex Technologies, Inc. (TSX:AHX)(OTCQB:ADHXF) today
announced the results on the two Sodium Thiosulfate (STS) Phase III
studies presented at the 2014 American Society of Clinical Oncology
(ASCO) Annual Meeting in Chicago, Illinois.
COG ACCL0431
David Freyer, DO, MS,
Children's Hospital Los Angeles, COG ACCL0431 Study Chair,
presented, "The Effects of Sodium Thiosulfate (STS) on
Cisplatin-induced Hearing Loss: A Report from the Children's
Oncology Group," in an oral presentation on June 1, 2014.
Study Design
COG Study ACCL0431, "A
Randomized Phase III Study of Sodium Thiosulfate for the Prevention
of Cisplatin-Induced Ototoxicity in Children," finished enrollment
of 131 patients in Q1 2012. The patients had been previously
diagnosed with childhood cancers.
The primary endpoint was to
evaluate the efficacy of STS for prevention of hearing loss in
children receiving cisplatin chemotherapy (hypothesis: 50% relative
reduction in hearing loss)
Secondary endpoints
included:
- Compare change in mean hearing thresholds
- Compare incidence of other Grade 3/4 toxicities (renal and
hematological)
- Monitor Event Free Survival (EFS) and Overall Survival (OS) in
two groups
Preliminary Results
126 eligible subjects were
enrolled with germ cell tumor (32), osteosarcoma (30),
neuroblastoma (26), medulloblastoma (26), hepatoblastoma (7) or
other (5). Of these 104 subjects (64 male and 29 <5 years old)
were evaluable for the primary endpoint.
Subjects were randomized
either to no treatment (control) or treatment with STS 16 grams/m2
IV over 15 minutes 6 hours after each cisplatin dose. Hearing was
measured using standard audiometry for age and data were reviewed
centrally using American Speech-Language-Hearing Association
criteria.
The proportion of subjects
with hearing loss assessed at 4 weeks post the final cisplatin dose
(primary endpoint) and EFS/OS (log-rank test, 2-year cumulative
estimates and Cox proportional hazards model) were compared between
the two groups.
- The proportion of hearing loss for STS vs. Control was 28.6%
(14/49) vs. 56.4% (31/55), respectively (p=0.004).
- Including all 126 subjects at median post-enrollment follow-up
of 2.9 years for censored patients, EFS for STS vs. Control was
61.2% vs. 69.9% (p=0.31); OS was 77.0% vs. 88.9% (p=0.029).
A subset analysis by extent of
disease determined post hoc was performed:
- For subjects with localized disease, EFS for STS (N=40) vs.
Control (N=38) was 72.5% vs. 68.3% (p=0.94); HR (hazard ratio) 1.03
(p=0.94); OS was 89.0% vs. 89.5% (p=0.48); HR 1.58 (p=0.48).
- For those with disseminated (metastatic) disease, EFS for STS
(N=21) vs. Control (N=26) was 41.6% vs. 72.5% (p=0.085); HR 2.13
(p=0.092); OS was 55.9% vs. 88.1% (p=0.011); HR 3.97
(p=0.019).
Preliminary Conclusions
- STS protects against cisplatin-induced hearing loss in
children, especially for those < 5 years old.
- In this study, use of STS did not result in lower EFS/OS in
patients with localized disease. However, the lower survival among
those with disseminated disease raises the concern of a tumor
protective effect when STS is administered on this dose and
schedule.
"Cisplatin-induced hearing
loss seriously diminishes quality of life by causing hearing loss
in many childhood cancer survivors and impairing their speech,
general learning, social development, and confidence," stated Dr.
Freyer, "The Children's Oncology Group is pleased to have
successfully completed the first pediatric cooperative group
clinical trial solely focused on finding a safe and effective means
for preventing cisplatin-induced hearing loss. We appreciate the
commitment Adherex has made to supporting this research and
preserving quality of life in this group of long-term
survivors."
SIOPEL 6
Edward A. Neuwelt, M.D.,
Professor at Oregon Health & Science University presented the
ongoing safety results from SIOPEL 6 on behalf of the SIOPEL 6
investigators and support team in a poster on June 2, 2014.
Study Design
SIOPEL 6 study, "A Multicenter
Open Label Randomized Phase III Trial of the Efficacy of Sodium
Thiosulfate in Reducing Ototoxicity in Patients Receiving Cisplatin
Chemotherapy for Standard Risk Hepatoblastoma," is being conducted
by The International Childhood Liver Tumour Strategy Group, SIOPEL.
The study was initiated in October 2007 and has enrolled 105 out of
a planned 115 patients (to achieve 102 evaluable). Interim efficacy
results on response to chemotherapy are evaluated after every 20
patients and reviewed by the Independent Data Monitoring Committee
(IDMC).
The primary objectives of the
study are:
- To assess the efficacy of STS to reduce the hearing impairment
caused by cisplatin
- To carefully monitor any potential impact of STS on response to
cisplatin and survival
The primary endpoint of the
study is centrally reviewed absolute hearing threshold, at the age
of ≥3.5 yrs, by pure tone audiometry, graded by Brock criteria.
Methods
- Newly diagnosed patients with standard risk hepatoblastoma are
treated with 4 chemotherapy courses every 2 weeks before surgery
and 2 courses after surgery.
- Patients are randomly assigned to receive cisplatin alone or
cisplatin followed by STS. Cisplatin 80 mg/m2 is administered i.v.
over 6 hrs.
- STS is administered i.v. exactly 6 hrs after stop of cisplatin
over 15 minutes at 20g/m2.
Interim Safety Results
The Independent Data
Monitoring Committee (IDMC) reviewed the efficacy results of the
trial after 20, 40, 60, and 80 patients to assess and rule out any
potential concern of an adverse effect of STS on the efficacy of
the cisplatin chemotherapy. The IDMC recommends the continuation of
the trial according to protocol.
"These results from David
Freyer et al are extremely encouraging for the SIOPEL 6 study.
SIOPEL 6 is a Phase III randomised trial looking at STS
otoprotection in cisplatin treated patients with standard risk
hepatoblastoma where the disease is localised, where there is a
tumour marker to follow response to treatment, and where survival
is over 90%," stated Penelope Brock, MD, PhD, FRCPCH, International
Chair of SIOPEL 6, "The average age at diagnosis is 18 months and
these children receive cisplatin monotherapy and surgery. The
majority of these children fall into the group <5 yrs at
diagnosis where they are likely to be cured with cisplatin alone
and surgery but they sustain bilateral permanent hearing loss for
life. Following the safety analysis of the first 80 patients on the
SIOPEL 6 trial the IDMC advises continuation of the trial.
Therefore if the otoprotection from STS is as good as in the trial
presented by Freyer et al then the SIOPEL 6 results are likely to
be very encouraging indeed. It is particularly in children with a
good prognosis and localised disease where cisplatin is the most
effective chemotherapy that we need to be testing otoprotective
drugs."
"We wish to thank Drs. Freyer,
Brock, and Neuwelt, and all of the participating investigators,
support teams and families for their commitment to completing these
studies," stated Mr. Rosty Raykov, Chief Executive Officer of
Adherex, "We believe the COG results combined with the ongoing
safety results from SIOPEL 6 are encouraging for the use of STS in
children with localized disease."
Adherex plans to discuss the
regulatory filing strategy for a New Drug Application (NDA) with
the FDA during the second half of 2014.
Conference Call
Adherex will host a conference
call at 3:00 p.m. Eastern Time (2:00 pm Central Time) today to
discuss the ASCO results.
Monday, June 2, 2014 @ 3pm Eastern
Time |
Toll Free: |
877-407-0784 |
International: |
201-689-8560 |
Webcast: |
http://public.viavid.com/player/index.php?id=109338 |
|
Replays Available through June 16, 2014: |
Toll Free: |
877-870-5176 |
International: |
858-384-5517 |
Passcode: |
13583100 |
About Sodium Thiosulfate
(STS)
STS is currently FDA-approved
as an antidote for cyanide poisoning. Adherex has licensed from
Oregon Health & Science University intellectual property rights
for the use of STS as a chemoprotectant, and are developing STS as
a protectant against the hearing loss often caused by
platinum-based anti-cancer agents in children. Preclinical and
clinical studies conducted by Oregon Health & Science
University and others have indicated that STS can effectively
reduce the incidence of hearing loss caused by platinum-based
anti-cancer agents. Adherex has received Orphan Drug Designation in
the United States for the use of STS in the prevention of platinum
induced ototoxicity in pediatric patients.
Hearing loss among children
receiving platinum-based chemotherapy is frequent, permanent and
often severely disabling. The incidence of hearing loss in these
children depends upon the dose and duration of chemotherapy, and
many of these children require lifelong hearing aids. There is
currently no established preventive agent for this hearing loss and
only expensive, technically difficult and sub-optimal cochlear
(inner ear) implants have been shown to provide some benefit.
Forward Looking Statements
Except for historical
information described in this press release, all other statements
are forward-looking. Forward-looking statements are subject to
certain risks and uncertainties inherent in the Company's business
that could cause actual results to vary, including such risks that
regulatory clinical and guideline developments may change,
scientific data may not be sufficient to meet regulatory standards
or receipt of required regulatory clearances or approvals, clinical
results may not be replicated in actual patient settings,
protection offered by the Company's patents and patent applications
may be challenged, invalidated or circumvented by its competitors,
the available market for the Company's products will not be as
large as expected, the Company's products will not be able to
penetrate one or more targeted markets, revenues will not be
sufficient to fund further development and clinical studies, the
Company may not meet its future capital needs, and its ability to
obtain additional funding, as well as uncertainties relative to
varying product formulations and a multitude of diverse regulatory
and marketing requirements in different countries and
municipalities, and other risks detailed from time to time in the
Company's filings with the Securities and Exchange Commission
including its Annual Report on Form 10-K for the year ended
December 31, 2013. Adherex Technologies, Inc. disclaims any
obligation to update these forward-looking statements except as
required by law.
For a more detailed discussion
of related risk factors, please refer to our public filings
available at www.sec.gov andwww.sedar.com.
Adherex Technologies Inc.Rosty RaykovChief Executive
Officer(919) 636-5144