PEDMARK™* has the potential to reduce the incidence and/or grade of chemotherapy-induced hearing loss and be the first available agent approved for this condition.
*PEDMARK is an investigational drug and has not yet been approved by the U.S. Food and Drug Administration (FDA) or any regulatory authority.
A unique formulation of sodium thiosulfate (STS)
Development
We believe PEDMARK is the only agent that is
specifically in development for the prevention of ototoxicity from cisplatin in
pediatric patients
PEDMARK is a small molecule, unique formulation
of STS
Drug Delivery
PEDMARK STS is administered 6 hours post completion of cisplatin infusion in an intravenous (IV) bolus dose over 15 minutes
Toxicology
STS is generally recognized as safe (GRAS) in the United States with respect to active ingredient STS but not established in current proposed use
Intended mechanism of action
Anticancer activity of cisplatin occurs during the first 2 hours after administration when the free (unbound) cisplatin distributes into the cancer cells1
Cisplatin is readily cleared from most organs but is longer term retained in the cochlea2
Cisplatin-induced ototoxicity is caused by irreversible damage to hair cells in the cochlea3
Cochlea is very sensitive to oxidative stress, which has been shown to be involved in ototoxicity4
STS inhibits oxidative stress5
Administering STS 6 hours after completion of cisplatin infusion ensures that levels of unbound cisplatin are minimal5
Two randomized studies have been completed
Proof of Concept Study | COG ACCL0431
131 patients with heterogenous solid tumors
Achieved primary efficacy endpoint – ASCO 2014
Final results published in Lancet Oncology, December 2016
Pivotal Study | SIOPEL 6
109
patients with standard risk hepatoblastoma (SR-HB)
Achieved
primary endpoint – SIOP 2017
Showed
no evidence of tumor protection
Final
results published in New England Journal of Medicine, June 2018
Granted Fast Track and Breakthrough Therapy Designation by the FDA
Completed NDA to FDA and MAA to EMA : PEDMARK (US) / PEDMARQSI (EU) is proposed to be indicated for the prevention of ototoxicity induced by cisplatin chemotherapy in patients 1 month to <18 years of age with localized, non-metastatic solid tumors.
Priority review granted upon acceptance by FDA.
FDA assigned PDUFA target action date of November 27, 2021. Prior FDA issued CRL was based on deficiencies with the facility of the drug product manufacturer identified during pre-approval inspection. No clinical or safety issues were identified.
Potential for 7.5 YEARS US market exclusivity with Pediatric Orphan Drug Designation
Patent protection in the US until 2039 for the for the unique anhydrous form of the active ingredient in Fennec’s PEDMARK product, as well as related methods of synthesis
EU regulatory milestones achieved
EMA validation received for MAA
Positive opinion on PIP received by PDCO at EMA
Potential for 10 YEARS EU market exclusivity with Pediatric-use Marketing Authorization (PUMA), if granted
PEDMARK has the potential to be the first and only therapy indicated in this area of significant high unmet medical need
Collaboration with Oregon Health and Science University (OHSU)
Fennec Pharma licensed 1 US and 9 foreign patents from OHSU for STS. The STS methods of use patents expire in Europe and Japan in 2021 and are currently pending in the US
Patent Protection was recently granted in the US until 2038 for method of use for children <5 years of age
References: 1. Cisplatin Injection [prescribing information ]. WG Critical Care, LLC., Paramus, NJ; February 2019. 2. Breglio AM, Rusheen AE, Shide ED, Fernandez KA, Spielbauer KK, McLachlin KM, et al. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun. 2017;8(1):1654. 3. Landier W. Ototoxicity and cancer therapy. Cancer. 2016;122(11):1647-1658. 4. Langer T, am Zehnhoff-Dinnesen A, Radtka S, Meitert J, Zolk O. Understanding platinum-induced ototoxicity. Trends Pharmacol Sci. 2013;34(8):458-469. 5. Data on file, Fennec Pharmaceuticals 2020.
PEDMARK™ is a registered trademark of Fennec Pharmaceuticals Inc.