- SIOPEL 6 met primary endpoint (p=0.002)
- 48% reduction in the incidence of hearing loss
- No evidence of tumor protection
RESEARCH TRIANGLE PARK, N.C., June 21, 2018 (GLOBE NEWSWIRE) — Fennec Pharmaceuticals Inc. (NASDAQ:FENC) (TSX:FRX), a specialty pharmaceutical company focused on the development of PEDMARK TM (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. “PEDMARK TM 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 PEDMARK TM. Fennec plans to pursue regulatory approval for PEDMARK TM 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 PEDMARK TM 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 PEDMARK TM (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 PEDMARK TM (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 PEDMARK TM 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 Raykov
Chief Executive Officer
Fennec Pharmaceuticals Inc.
T: (919) 636-5144