Sodium thiosulfate

38828006

New Medicines

Pedmark (US) · Hearing loss due to cisplatin chemotherapy in children - prevention

Information

Pedmark (US)
New formulation
Fennec
Fennec

Development and Regulatory status

Pre-registration (Filed)
Pre-registration (Filed)
Pre-registration (Filed)
Yes
Feb 20 · According to its latest annual report, Fennec is planning for commercial launch of sodium thiosulfate for infusion, if approved, in H1 2021 in Europe and in H2 20 in the US. Specific plans for UK launch not described [8].
Feb 20 · EMA accepts MAA application for sodium thiosulfate infusion for prevention of ototoxicity induced by cisplatin chemotherapy in patients one month to <18 years of age with localized, non-metastatic, solid tumors [7].
Dec 18 · Fennec Pharmaceuticals initiated a rolling NDA submission for Pedmark for the prevention of ototoxicity induced by cisplatin chemotherapy in patients of age 1 month to less than 18 years with localised, non-metastatic, solid tumours. Approval is anticipated H2 2019 [6].
Aug 18 · Pediatric committee (PDCO) of the EMA accepts the Fennec paediatric investigation plan (PIP) for Pedmark for prevention of platinum-induced ototoxic hearing loss for standard risk hepatoblastoma (SR-HB). The company was also advised that Pedmark is eligible for submission of an application for a Pediatric Use Marketing Authorisation (PUMA) [5].
Mar 18 · Granted breakthrough therapy designation in US for prevention of cisplatin-related ototoxicity in paediatric patients with standard risk hepatoblastoma. The designation was granted based on the safety and efficacy results from the SIOPEL 6 and COG ACCL0431 studies [5].
Mar 18 · Granted fast track status in US for prevention of cisplatin-related ototoxicity in pediatric patients with standard risk hepatoblastoma [5].
Oct 17 · Regulatory submissions are planned in the EU and US in 2018 [3].
Sep 14 · PIII study is taking place in the US, Australia and Canada [2].
Sep 14 · PIII [1].

Category

Sodium thiosulfate is a chemoprotectant/antioxidant. It inactivates platinum complexes by binding electrophilic platinum with with thiol, thus forming a covalent complex that is not cytotoxic and can be excreted rapidly.
Platinum compounds, such as cisplatin, have significant adverse effects including ototoxicity and associated permanent hearing loss. The effect of hearing loss in young children is significant and can influence speech and language development, educational achievement, and social-emotional development. Approximately 60% of children treated with cisplatin develop permanent bilateral hearing loss.
Hearing loss due to cisplatin chemotherapy in children - prevention
Intravenous

Further information

Yes
To be confirmed

Trial or other data

Oct 17 · Positive results from the PIII SIOPEL 6 study (NCT00652132) announced. The study met its primary endpoint. The study demonstrated that the addition of sodium thiosulfate (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%) treated with cisplatin alone and in 20/54 (37%) treated with Cis+STS, corresponding to a relative risk of 0.56 (p=0.0033) [3].
Jan 17 · Results from ACCL0431 trial published in the Lancet Oncology [4].
Dec 16 · Fennec Pharmaceuticals completed the PIII ACCL0431 trial (NCT00716976; n=126) which met the primary endpoints of prevention of cisplatin-induced hearing loss in children. Cisplatin-induced hearing loss occurred in 29% of patients who received sodium thiosulfate prophylaxis, compared with 56% of those who did not receive prophylactic treatment (p = 0.004). A reduced overall survival rate in patients with disseminated metastatic disease raised the possibility that STS treatment may have a tumour protective effect [3].
Apr 14 · The study is ongoing but no longer recruiting pts [2].
Jun 08 · A PIII (NCT00716976) study began recruitment of 131 children aged 1 to 18 years, to study sodium thiosulfate to see how well it works in preventing hearing loss in young patients receiving cisplatin for newly diagnosed germ cell tumor, hepatoblastoma, medulloblastoma, neuroblastoma, osteosarcoma, or other malignancy. Sodium thiosulfate is administered by IV at 16g/m2 (or 533mg/kg for patients whose therapeutic protocol administers cisplatin on a per kg basis due to young age or small body mass) over 15 minutes, beginning 6 hours after the completion of each cisplatin infusion until the completion of cisplatin therapy. The study is expected to compete Sep 12. Primary outcome is Incidence of hearing loss, defined by comparing hearing sensitivity at follow up evaluation (4 weeks following the last dose of cisplatin) relative to baseline measurements using ASHA criteria. The proportion of patients treated with sodium thiosulfate who develop hearing loss will be compared with that of patients who did not receive the study drug [2].

Evidence based evaluations

Hearing loss due to chemotherapy

Information

Licence extension / variation
Hope Pharmaceuticals
Hope Pharmaceuticals

Development and Regulatory status

None
None
Pre-registration (Filed)

Jun 18: Hope Pharmaceuticals files sNDA for treatment of patients with chemotherapy induced damage in USA [1].

Category

Sodium thiosulfate is a chemoprotectant/antioxidant. It inactivates platinum complexes by binding electrophilic platinum with with thiol, thus forming a covalent complex that is not cytotoxic and can be excreted rapidly.
Platinum compounds, such as cisplatin, have significant adverse effects including ototoxicity and associated permanent hearing loss. The effect of hearing loss in young children is significant and can influence speech and language development, educational achievement, and social-emotional development. Approximately 60% of children treated with cisplatin develop permanent bilateral hearing loss.
Hearing loss due to chemotherapy
Intravenous

Calciphylaxis - treatment of associated pain in chronic haemodialysis patients

Information

Licence extension / variation
Hope Pharmaceuticals
Hope Pharmaceuticals

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials
Yes
Yes

Category

The mechanism by which sodium thiosulfate treats calciphylaxis is not clear. Sodium thiosulfate induces calcium removal through chemical chelation, and thus reduces the risk factor of dysregulation of the calcium and phosphorous metabolism.
Prevalence of calciphylaxis is estimated to be 5.0 per 100,000 population; using the latest midyear population estimates for England Wales this would equate to 2,919 persons. The UK Calciphylaxis Study states that calciphylaxis occurs in about one case per year for every 600 dialysis patients in the UK; there are estimated to be around 30,000 people on dialysis in the UK, which equates to 50 cases per year [3].
Calciphylaxis - treatment of associated pain in chronic haemodialysis patients
Intravenous