Full Press Release Details
Fennec Pharmaceuticals
Announces FDA Approval of PEDMARK
(Sodium Thiosulfate Injection)
PEDMARK is the First and Only FDA-Approved Therapy Indicated
to Reduce the Risk of Ototoxicity Associated with Cisplatin in Pediatric Patients with Localized, Non-Metastatic Solid Tumors ~
TRIANGLE PARK, N.C., Sept. 21, 2022 (GLOBE NEWSWIRE) -- Fennec Pharmaceuticals Inc. (NASDAQ: FENC; TSX: FRX), a specialty pharmaceutical
company, today announced that the U.S. Food and Drug Administration (FDA) has approved PEDMARK (sodium
thiosulfate injection) to reduce the risk of ototoxicity associated with cisplatin in pediatric patients one month of age and older with
localized, non-metastatic solid tumors. This approval makes PEDMARK the first and only treatment approved by the FDA in this area of
significant unmet medical need.
"The FDA approval of
PEDMARK represents an important breakthrough for pediatric patients with localized, non-metastatic solid tumors at risk for cisplatin-induced
hearing loss. Cisplatin is a critical, standard of care agent, used in the treatment of pediatric cancers; however, even though effective,
it could be harmful to children, frequently causing permanent and irreversible bilateral hearing loss. With PEDMARK, physicians now have
an approved treatment option to reduce the risk of cisplatin-induced hearing loss in pediatric patients," said Rosty Raykov, chief
executive officer of Fennec Pharmaceuticals. "We would like to thank the patients, their families, physicians, investigators, employees,
consultants and the entire research team at Oregon Health and Science University, who have contributed to the development of PEDMARK."
The FDA approval of PEDMARK
was based upon safety and efficacy data from two pivotal open-label, randomized Phase 3 trials (SIOPEL 6 and COG ACCL0431), which compared
PEDMARK plus cisplatin-based regimen to cisplatin-based regimens alone for the reduction of cisplatin-induced hearing loss in pediatric
patients. In both studies, the incidence of hearing loss was consistently and significantly lower in the PEDMARK plus cisplatin arm compared
with the cisplatin alone arm [21.4% vs. 73.3% (p = 0.005) and 32.7% vs. 63% (p = 0.002) with hearing loss in COG ACCLO431 and SIOPEL6,
respectively]. The most common adverse reactions ( 25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL6
are vomiting, infection, nausea, decreased hemoglobin, and hypernatremia. The most common adverse reaction ( 25% with difference between
arms of >5% compared to cisplatin alone) in COG ACCL0431 is hypokalemia.
"Historically, there
have been no approved treatments for preventing cisplatin-induced hearing loss. As a physician focused in pediatric cancer for many years,
and a primary investigator in the pivotal PEDMARK Phase 3 Clinical Oncology Group (COG) trial, the FDA approval of PEDMARK addresses an
enormous unmet need and for many children and young adults, has the potential to greatly improve everyday activities for
these patients," said David R. Freyer, DO, MS, Primary Investigator, COG ACCL0431, and Director of the Survivorship & Supportive
Care Program, Cancer and Blood Disease Institute, Children's Hospital Los Angeles.
in chemotherapy-based treatment approaches for pediatric patients with localized, solid tumors have improved, resulting in an 85 percent
or higher five-year survival rate for these patients2. However, use of platinum-based chemotherapy, still the treatment
of choice in many cases, can be toxic to the ears and cisplatin treatment frequently causes permanent and irreversible bilateral (affecting
both ears) hearing loss. Permanent hearing loss can be seen in approximately 60 percent of children treated with cisplatin and can be
as high as 90 percent.1,2 Until now, interventions with management strategies such as cochlear implants and hearing aids
only occurred after hearing loss had been detected and these interventions do not return normal hearing.3
loss can have a profound impact on a person's life, especially in children who are critically dependent upon normal hearing for
cognitive, psychosocial, and speech development," said Penelope "Peppy" R. Brock, M.D., Ph.D., of Great Ormond Street
Hospital in London and International Chair of the SIOPEL 6 trial. "Incorporating PEDMARK into current
treatment strategies with the goal to preserve hearing in children and young adults without reducing the effectiveness of their cisplatin
treatment - is a welcome step towards helping to improve long-term outcomes for these patients."
For more information about
product availability and patient support, please contact the Fennec HEARS program at 1-833-7PEDMARK (1-833-773-3627).
The FDA granted this application
Priority Review designation. PEDMARK also received Orphan Drug designation by the FDA in 2004.
The Marketing Authorization
Application (MAA) for sodium thiosulfate (tradename PEDMARQSI) is currently under evaluation by the European Medicines Agency (EMA).
Cisplatin-Induced Ototoxicity
Cisplatin and other platinum compounds are essential chemotherapeutic agents for the treatment
of many pediatric malignancies. Unfortunately, platinum-based therapies can cause ototoxicity, or hearing loss, which is permanent, irreversible,
and particularly harmful to the survivors of pediatric cancer.4
incidence of ototoxicity depends upon the dose and duration of chemotherapy, and many of these children require lifelong hearing aids
or cochlear implants, which can be helpful for some, but do not reverse the hearing loss and can be costly over time.5 Infants
and young children that are affected by ototoxicity at critical stages of development lack speech and language development and literacy,
and older children and adolescents often lack social-emotional development and educational achievement.6
PEDMARK (sodium thiosulfate injection)
PEDMARK is the first and only U.S.
Food and Drug Administration (FDA) approved therapy indicated to reduce the risk of ototoxicity associated with cisplatin treatment in
pediatric patients with localized, non-metastatic, solid tumors. It is a unique formulation of sodium thiosulfate in single-dose, ready-to-use
vials for intravenous use in pediatric patients.7 PEDMARK is also the only therapeutic agent with
proven efficacy and safety data with an established dosing paradigm, across two open-label, randomized Phase 3 clinical studies, the
Clinical Oncology Group (COG) Protocol ACCL0431 and SIOPEL 6.
In the U.S. and Europe, it
is estimated that, annually, more than 10,000 children may receive platinum-based chemotherapy. The incidence of ototoxicity 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 that suffer ototoxicity at critical stages of development lack speech
language development and literacy, and older children and adolescents lack social-emotional development and educational achievement.
PEDMARK (sodium thiosulfate injection) is indicated to reduce the risk of ototoxicity associated
with cisplatin in pediatric patients 1 month of age and older with localized, non-metastatic solid tumors.
The safety and efficacy of PEDMARK have not been established when administered following cisplatin infusions longer
than 6 hours. PEDMARK may not reduce the risk of ototoxicity when administered following longer cisplatin infusions, because irreversible
ototoxicity may have already occurred.
PEDMARK is contraindicated in patients with history of a severe hypersensitivity to sodium thiosulfate or
any of its components.
Hypersensitivity reactions
occurred in 8% to 13% of patients in clinical trials. Monitor patients for hypersensitivity reactions. Immediately discontinue PEDMARK
and institute appropriate care if a hypersensitivity reaction occurs. Administer antihistamines or glucocorticoids (if appropriate) before
each subsequent administration of PEDMARK. PEDMARK may contain sodium sulfite; patients with sulfite sensitivity may have hypersensitivity
reactions, including anaphylactic symptoms and life-threatening or severe asthma episodes. Sulfite sensitivity is seen more frequently
in people with asthma.
PEDMARK is not indicated
for use in pediatric patients less than 1 month of age due to the increased risk of hypernatremia or in pediatric patients with metastatic
Hypernatremia occurred in
12% to 26% of patients in clinical trials, including a single Grade 3 case. Hypokalemia occurred in 15% to 27% of patients in clinical
trials, with Grade 3 or 4 occurring in 9% to 27% of patients. Monitor serum sodium and potassium at baseline and as clinically indicated.
Withhold PEDMARK in patients with baseline serum sodium greater than 145 mmol/L.
for signs and symptoms of hypernatremia and hypokalemia more closely if the glomerular filtration rate (GFR) falls below 60 mL/min/1.73m2.
Administer antiemetics prior
to each PEDMARK administration. Provide additional antiemetics and supportive care as appropriate.
The most common adverse reactions
( 25% with difference between arms of >5% compared to cisplatin alone) in SIOPEL6 were vomiting, nausea, decreased hemoglobin,
and hypernatremia. The most common adverse reaction ( 25% with difference between arms of >5% compared to cisplatin alone) in COG
ACCL0431 was hypokalemia.
see full Prescribing Information for PEDMARK at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212937s000lbl.pdf.
Fennec Pharmaceuticals Inc. is a specialty
pharmaceutical company focused on the development and commercialization of PEDMARK for the prevention of platinum-induced
ototoxicity in pediatric patients. Further, PEDMARK received FDA approval in September 2022 and has received Orphan Drug Designation
in the U.S. Fennec has a license agreement with Oregon Health and Science University (OHSU) for exclusive worldwide license