Efficacy: 11 patients (8 PH1 and 3 PH2 reached by day 120 receiving once-monthly nedosiran 9/11 (82%) had achieved normal or near-normal urinary oxalate (Uox) levels, defined as below 0.46 mmol/1.73 m2 body surface area adjusted (BSA)/24 hr (laboratory assay upper limit of normal [ULN]) and from 0.46 to 0.6 mmol/1.73 m2 BSA/24 hr (1.3xULN, defined per protocol as near-normal), respectively
Safety: No drug-related severe adverse events; 3 injection-site reactions and 1 serious AE that was unrelated to Nedosiran); AE profile comparable to that of PHYOX1 (Phase 1)
Based on the cumulative number of days, total patient exposure to monthly dosing of nedosiran delivered subcutaneously has reached 5.8 years
Dicerna has created a first-in-class molecule Nedosiran (silencing lactate dehydrogenase A (LDHA)) to treat PH1 (AGXT gene mutation), PH2 (GRHPR gene mutation) and PH3 (HOGA1 gene mutation)
Nedosiran has been granted orphan drug designation for PH (2018), breakthrough therapy for PH1 (2019), rare pediatric disease designation for PH (2020) by FDA; Is in discussion for a potential expansion of the Breakthrough Therapy Designation to include PH2
With PHYOX3 showing positive signals, Dicerna is one step closer to NDA submission of Nedosiran for the treatment of PH1 and PH2
Results from patients with PH1 are very encouraging, but only 1/3 patients with PH2 achieved normalization at day 120
Due to COVID-19, Dicerna changed its guidance of enrollment completion for its registrational PHYOX2 trial (for PH1 and PH2) from Q2 to Q4 2020; Any further delays will be detrimental to trial enrolment because Alnylam’s Lumasiran’s (PH1) PDUFA date is scheduled for Dec 3, 2020
To support its submission package of PHYOX2 and PHYXO3, Dicerna has planned additional supportive studies:
PHYOX4: In patients with PH3; Enrollment initiation expected in Q3 2020
PHYOX7: In patients with PH1, PH2; Enrollment initiation expected in Q4 2020
PHYOX8: In patients with PH1, PH2; Enrollment initiation expected in Q1 2021
PHYOXOBX: In patients with PH3; Study initiation expected in Q3 2020
An NDA in US by Q3’21 and subsequent filings are expected in Europe and then Japan; Nedosiran market approval is expected in 2022