Mr. Rosty Raykov reports

FENNEC ANNOUNCES POSITIVE RESULTS FROM PHASE 3 SIOPEL 6 STUDY ON PEDMARK (SODIUM THIOSULFATE) PRESENTED AT THE 49TH CONGRESS OF THE INTERNATIONAL SOCIETY OF PEDIATRIC ONCOLOGY (SIOP) 2017 MEETING

Fennec Pharmaceuticals Inc. has released data from its phase 3 SIOPEL 6 study, which were presented during the late breaker session on Saturday, Oct. 14, 2017, at SIOP 2017 in Washington.

Top-line efficacy data

The SIOPEL 6 study met its primary end point. The study demonstrated that the addition of sodium thiosulphate (STS) significantly reduces the incidence of cisplatin-induced hearing loss without any evidence of tumour protection. Among the 99 evaluable patients, hearing loss occurred in 30/45 (67 per cent) treated with cisplatin (Cis) alone and in 20/54 (37.0 per cent) treated with Cis plus STS, corresponding to a relative risk of 0.56 (P equals 0.0033).

Fennec plans to pursue regulatory approval for Pedmark based on the data from the SIOPEL 6 study along with the proof of principle data from COG ACCL0431. STS has received orphan drug designation in the United States in this setting and plans to pursue European market exclusivity for pediatric use upon approval.

"I am absolutely delighted that after 30 years of research we have found a safe way to reduce ototoxicity in children receiving platinum containing chemotherapy," said Dr. Penelope Brock, MD, PhD, international chair of SIOPEL. "This means that children who are cured from cancer after receiving platinum treatment can look forward to a normal healthy life, fully integrated into society. I believe this marks a new standard of care in pediatric oncology."

The company also reported top-line data for secondary end points event free survival (EFS) and overall survival (OS). The combination of Cis plus STS was generally well tolerated. With a follow-up of 52 months, three-year EFS is Cis 78.8 per cent and Cis plus STS 82.1 per cent; three-year OS is Cis 92.3 per cent and Cis plus STS 98.2 per cent.

"We are very pleased with the results of this study," stated Rosty Raykov, chief executive officer of Fennec. "We would like to thank all the patients and their families who participated in this trial, physicians, the entire SIOPEL 6 team, and Dr. Neuwelt and his research team at OHSU. We believe that if approved Pedmark would be an important therapy for patients and caregivers where currently there are no treatment options."

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 presents the toxicities of the two arms.

          TOXICITIES OF THE TWO ARMS

Adverse event       Grade     CIS      CIS+STS 
   
                            N     %    N     %  
 
Febrile neutropenia     3   7  13.5    5   8.8 
                        4   -     -    -     -   
Infection               3   5   9.6    6  10.5
                        4   -     -    -     -   
Hypomagnesemia          3   1   1.9    1   1.8 
                        4   -     -    -     -   
Hypernatremia           3   -     -    1   1.8 
                        4   -     -    -     -   
Vomiting                3   1   1.9    3   5.3 
                        4   -     -    -     -   
Nausea                  3   3   5.8    2   3.5 
                        4   -     -    -     -

SIOP 2017 presentation

Fennec will provide access to the recording of SIOP 2017 late breaker presentation on the company's website. To access the archived recording, visit the Fennec website.

SIOPEL 6

SIOPEL 6 is a multicentre 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 11 countries enrolled 113 evaluable patients. The study is closed to recruitment and all protocol prespecified IDMC safety reviews are now complete. The primary efficacy hearing end point 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 per cent power and a 5-per-cent significance level to detect an absolute 25-per-cent reduction in the rate of Brock grade equals 1 hearing loss with a chi-square test, from a 60-per-cent hearing loss in Cis alone arm to a 35-per-cent hearing loss in Cis plus STS arm. The primary end point is the rate of Brock grade equals 1 hearing loss determined after the end of treatment at the age of equals 3.5 years by pure tone audiometry.

About Pedmark (sodium thiosulphate/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.

In the United States and Europe it is estimated that over 7,000 children are diagnosed with local cancers that may receive platinum-based chemotherapy. Localized cancers that receive platinum agents may have overall survival rates of greater than 80 per cent further emphasizing the 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 suboptimal 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 co-operative groups in two phase 3 clinical studies of survival and reduction of ototoxicity, the clinical oncology group protocol ACCL0431 and SIOPEL 6. Both studies are closed to recruitment. The COG ACCL0431 protocol enrolled one of five childhood cancers typically treated with intensive cisplatin therapy for localized and disseminated disease, including newly diagnosed hepatoblastoma, germ cell tumour, osteosarcoma, neuroblastoma and medulloblastoma. SIOPEL 6 enrolled only hepatoblastoma patients with localized tumours. COG ACCL0431 final results were published in the Lancet Oncology.

In May, 2017, Fennec announced the launch of a named patient program in Europe. European-based health care professionals can obtain details about STS named patient program by emailing clinical@fennecpharma.com.

About Fennec Pharmaceuticals Inc.

Fennec Pharmaceuticals is a specialty pharmaceutical company focused on the development of sodium thiosulphate (STS) for the prevention of platinum-induced ototoxicity in pediatric patients. STS has received orphan drug designation in the U.S. in this setting. Fennec has an exclusive licence agreement with OHSU for exclusive worldwide licence rights to intellectual property directed to STS and its use for chemoprotection, including the prevention of ototoxicity induced by platinum chemotherapy, in humans.

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