Fennec Pharmaceuticals Inc. (NASDAQ:FENC) (TSX:FRX), a specialty
pharmaceutical company focused on the development of PEDMARKTM (a
unique formulation of sodium thiosulfate (STS)), announced today a
publication in the June 21, 2018 issue of the New England Journal
of Medicine (NEJM) for STS in the prevention of cisplatin induced
ototoxicity in pediatric patients.
The NEJM publication provides the final results
from the SIOPEL 6 study, a multi-centre open label randomized phase
3 study evaluating the efficacy of STS in reducing ototoxicity in
patients receiving cisplatin monotherapy for standard risk
hepatoblastoma. It includes hearing assessments in 101 patients and
52 month median follow up of 3 year event-free survival and 3 year
overall survival data.
"I am thrilled that after 30 years of research
we have found a drug which prevents the horrible life-long hearing
loss which children receiving cisplatin chemotherapy pay as the
price for cure of their cancer,” said Penelope Brock,
M.D., Ph.D., M.A., International Chair of SIOPEL 6 and first
author of the NEJM paper. “PEDMARKTM could help ensure that parents
aren’t faced with an upsetting scenario where successful cancer
treatment comes at the cost of their child’s hearing. Importantly,
children should be free to live normal healthy lives and be able to
forget that they ever had cancer as a child. Today is a great and
memorable day!"
In March 2018, Fennec Pharmaceuticals was
granted Fast Track designation and Breakthrough Therapy designation
for PEDMARKTM. Fennec plans to pursue regulatory approval for
PEDMARKTM based on the data from the SIOPEL 6 study along with the
data from Children Oncology Group (COG) ACCL0431 study. Fennec
anticipates commencing regulatory submissions in the fourth quarter
of 2018. STS has received Orphan Drug Designation in the US in this
setting and plans to pursue European Market Exclusivity for
Pediatric Use upon approval.
"It is exciting to see the NEJM share the
positive impact and importance of PEDMARKTM in pediatric cancer
with the broader clinical and research communities," said Rosty
Raykov, CEO of Fennec. "After a long journey, this is a major step
forward to reduce the number of children that will require lifelong
and suboptimal hearing aids and cochlear implants. On behalf of
Fennec we would like to thank the patients, their families and the
physicians whose dedication and efforts have made this clinical
study possible."
Overview of Data Published in
NEJM
The SIOPEL 6 study met its primary endpoint.
Sodium thiosulfate, administered 6 hours after cisplatin
chemotherapy, reduced the incidence of cisplatin-induced hearing
loss in children with standard-risk hepatoblastoma without
jeopardizing overall or event-free survival.
The absolute hearing threshold was assessed in
101 children. Hearing loss of grade 1 or higher occurred in 18 of
55 children (33%) in the cisplatin–sodium thiosulfate group, as
compared with 29 of 46 (63%) in the cisplatin-alone group,
indicating a 48% lower incidence of hearing loss in the
cisplatin–sodium thiosulfate group (relative risk, 0.52; 95%
confidence interval [CI], 0.33 to 0.81; P = 0.002). At a median of
52 months of follow-up, the 3-year rates of event-free survival
were 82% (95% CI, 69 to 90) in the cisplatin–sodium thiosulfate
group and 79% (95% CI, 65 to 88) in the cisplatin-alone group, and
the 3-year rates of overall survival were 98% (95% CI, 88 to 100)
and 92% (95% CI, 81 to 97), respectively.
Safety and Tolerability
In the study, the results presented showed that
treatment was well tolerated and acute toxicity similar and
expected between arms. The table below presents the numbers of
children with adverse events of grade 3 or 4:
|
Children with Grade 3 or 4 Adverse
Events.* |
|
|
|
Adverse Event and Grade |
Cisplatin Alone(N = 52) |
Cisplatin–Sodium Thiosulfate(N =
57) |
|
no. of patients (%) |
|
|
Allergy, grade 3 |
1
(2) |
0 |
Febrile neutropenia, grade 3 |
10
(19) |
8 (14) |
Infection, grade 3 |
16
(31) |
13 (23) |
Hypomagnesemia, grade 3 |
1
(2) |
1 (2) |
Hypernatremia, grade 3 |
0 |
1 (2) |
Vomiting, grade 3 |
2
(4) |
4 (7) |
Nausea, grade 3 |
3
(6) |
2 (4) |
Left ventricular systolic dysfunction, grade 3 or 4 |
0 |
0 |
Renal event, grade 3 or 4 |
0 |
0 |
Anemia |
|
|
Grade 3 |
8
(15) |
10 (18) |
Grade 4 |
0 |
1 (2) |
Leukopenia, grade 3 |
2
(4) |
2 (4) |
Neutropenia |
|
|
Grade 3 |
3
(6) |
7 (12) |
Grade 4 |
3
(6) |
3 (5) |
Thrombocytopenia |
|
|
Grade 3 |
1
(2) |
1 (2) |
Grade 4 |
1
(2) |
1 (2) |
Gastrointestinal event |
2
(4) |
3 (5) |
Elevated liver-enzyme level |
|
|
Grade 3 |
6
(12) |
3 (5) |
Grade 4 |
0 |
1 (2) |
Elevated serum glucose level, grade 3 |
2
(4) |
1 (2) |
Hypermagnesemia, grade 3† |
2
(4) |
5 (9) |
Hypophosphatemia, grade 3 |
0 |
5 (9) |
Hyperkalemia, grade 3 |
2
(4) |
0 |
Hypokalemia |
|
|
Grade 3 |
0 |
4 (7) |
Grade 4 |
0 |
1 (2) |
Dyspnea, grade 3 |
1 (2) |
0 |
* If grade 4 is not shown, there was no grade 4
adverse event. This table includes adverse events that were
associated with additional treatment (mostly doxorubicin) given to
children in each group.† The protocol specified the addition of
magnesium to the hydration fluid administered with cisplatin
therapy.
SIOPEL 6
SIOPEL 6 is a multi-centre open label randomized
phase 3 study evaluating the efficacy of STS in reducing
ototoxicity in patients receiving cisplatin monotherapy for
standard risk hepatoblastoma. From the beginning of 2007 to
the end 2014, 52 sites from 12 countries enrolled 113 evaluable
patients. The study is closed to recruitment and all protocol
pre-specified IDMC safety reviews are now complete. The
primary efficacy hearing endpoint analysis can be performed once
patients have reached 3.5 years of age and an audiometry test can
be carried out. The SIOPEL 6 study trial was designed with 80%
power and a 5% significance level to detect an absolute 25%
reduction in the rate of Brock grade ≥1 hearing loss with a
chi-square test, from a 60% hearing loss in Cis alone arm to a 35%
hearing loss in Cis+STS arm. The primary endpoint is the rate of
Brock grade ≥ 1 hearing loss determined after the end of treatment
at the age of ≥3.5 years by pure tone audiometry.
About PEDMARKTM (sodium thiosulfate/STS)
Cisplatin and other platinum compounds are
essential chemotherapeutic components for many pediatric
malignancies. Unfortunately, platinum-based therapies cause
ototoxicity in many patients, and are particularly harmful to the
survivors of pediatric cancer.
Each year in the U.S. and Europe there is
estimated that over 10,000 children with solid tumors are treated
with platinum agents. The vast majority of these newly
diagnosed tumors are localized and classified as low to
intermediate risk in nature. These localized cancers may have
overall survival rates of greater than 80%, further emphasizing the
importance of quality of life after treatment. 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. Infants and young children at critical stages
of development lack speech language development and literacy, and
older children and adolescents lack social-emotional development
and educational achievement.
STS has been studied by cooperative groups in
two Phase 3 clinical studies of survival and reduction of
ototoxicity: COG ACCL0431 and SIOPEL 6. Both studies are closed to
recruitment. COG ACCL0431 enrolled one of five childhood cancers
typically treated with intensive cisplatin therapy for localized
and disseminated disease, including newly diagnosed hepatoblastoma,
germ cell tumor, osteosarcoma, neuroblastoma, and
medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma
patients with localized tumors. COG ACCL0431 final results were
published in the Lancet Oncology. SIOPEL 6 final results were
published in the New England Journal of Medicine.
About Fennec
Pharmaceuticals
Fennec Pharmaceuticals Inc., is a specialty
pharmaceutical company focused on the development of PEDMARKTM (a
unique formulation of sodium thiosulfate (STS)) for the prevention
of platinum-induced ototoxicity in pediatric patients. STS has
received Orphan Drug Designation in the US in this setting. Fennec
has a license agreement with Oregon Health and Science University
(OHSU) for exclusive worldwide license rights to intellectual
property directed to STS and its use for chemoprotection, including
the prevention of ototoxicity induced by platinum chemotherapy, in
humans. For more information, please visit
www.fennecpharma.com.
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 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 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, 2017. Fennec Pharmaceuticals, Inc. disclaims any
obligation to update these forward-looking statements except as
required by law.
The scientific information discussed in this
news release related to PEDMARKTM is preliminary and investigative.
Such product candidates are not approved by the U.S. Food and Drug
Administration, Health Canada or other regulatory and no
conclusions can or should be drawn regarding the safety or
effectiveness of such product candidate.
For a more detailed discussion of related risk
factors, please refer to our public filings available at
www.sec.gov and www.sedar.com.
For further information, please
contact:
Rosty RaykovChief Executive OfficerFennec
Pharmaceuticals Inc.T: (919) 636-5144
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