Risdiplam

Detailed information

General information about assessment reports

Since 2006, an Environmental Risk Assessment (ERA) for the active pharmaceutical substance shall accompany an application for a marketing authorisation in EU for a medicinal product for human use. Parts of environmental data are available in the public assessment report (PAR/EPAR for centrally approved medicines). Environmental considerations are not included in the benefit-risk assessment for human medicines. If new data emerge after approval that necessitate an update of the environmental risk assessment, a variation application (“type IB C.I.z variation”) must be submitted to the regulatory authority.

Assessment report

Assessment report for Evrysdi (risdiplam), Roche Registration GmbH, typ II-variation, 27 March 2025, EMA/130688/2025.

Hazard

Persistence: No data.

Bioaccumulation: Risdiplam is not considered bioaccumulative, with log K_ow values of 0.69 at pH 5.0, 2.37 at pH 7.0, and 2.63 at pH 9.0. The measured bioconcentration factor (BCF) was < 3 at pH 7.0.

Comment: The text states that “The ion-corrected log D_ow values for diflunisal at pH levels 5, 7, and 9 are recorded as 0.69, 2.37, and 2.63, respectively. Therefore, a screening for PBT of diflunisal will not be required.” As these log D values correspond to those reported for risdiplam in Table 1, the reference to diflunisal is considered a typographical error. The same log D values at pH 5, 7, and 9 (0.69, 2.37, and 2.63, respectively) are reported for risdiplam in fass.se, supporting the conclusion that the statement was intended to refer to risdiplam.

Toxicity: No data.

Risk

The risk, PEC/PNEC, calculated from data in the assessment report from a European perspective:

PEC _{Surface water refined} = 0.0009 mikrog/L. Below the threshold of 0.01.

Risdiplam has only undergone a phase I study in accordance with regulatory requirements for environmental risk assessments (Guideline on the environmental risk assessment of medicinal products for human use, EMEA/CHMP/SWP/4447/00 Rev. 1- Corr.) A phase I study includes data on bioaccumulation and an estimation of the environmental concentration of risdiplam (PEC_{Surface water}). If the specified threshold values are not exceeded, the company is not required to conduct a Phase II study, which includes data on toxicity, persistence, and risk assessment based on PEC/PNEC.

Fass environmental information

Fass environmental information for Evrysdi from Roche (retrieved on 2026-09-02).

Hazard

Persistence: Risdiplam is not readily biodegradable. In an OECD 301 F test, no biodegradation was observed after 28 days, based on the ratio of biological oxygen demand (BOD) to theoretical oxygen demand (ThOD), supporting the conclusion that risdiplam is potentially persistent.

Bioaccumulation: Risdiplam has a low potential for bioaccumulation, as the log D at pH 7 was 2.37 (OECD 107) and 0.58 (OECD 117), both below the threshold value of 4.

Acute toxicity: There are data for 3 trophic levels, most sensitive algae NOEC 344 microg/L.

Risk

PEC/PNEC is based on total sold amount API (active pharmaceutical ingredient) in Sweden year 2025.

PEC = 0.00004 microg/L.

PNEC = Lowest NOEC, 344 microg/L/1000 (Assessment Factor (AF) for 3 acute studies) = 0.344 microg/L.

PEC/PNEC = 0.00013 which gives the risk insignificant.