Directions Spring 2020

Research Update

A clinical trial, also called an interventional study, tests new drugs and treatments. It can also test new applications for approved drugs or treatments (e.g., using drugs in different combinations or for different diseases). A drug must pass each individual phase of a clinical trial before advancing.

PHASE 1

PHASE 2

PHASE 3

PHASE 4

Increases the number of people test- ed—up to 100-200 including the control or placebo group. A drug that passes these three phases can be approved and marketed to the general public.

Primarily involves ongoing evaluation and monitoring, even after a drug is approved for the general public.

Tests safety and dosage levels, usually on 10-20 individuals. Sometimes, these volunteers are healthy individuals. However, for an orphan disease like SMA, some or all may be patients with the condition being studied.

Tests a slightly larger group, usually 20-40 individuals, all of whom have the condition being studied.

Recruiting and Ongoing Clinical Trials for SMA Genentech , a member of the Roche group, is assessing the safety and efficacy of risdiplam in its clinical trials RAIN- BOWFISH (currently recruiting), JEWELFISH, SUNFISH, and FIREFISH (ongoing). Risdiplam is an investigational, oral med- icine that is systemically distributed and designed to increase SMN protein levels in the central nervous system (CNS) and throughout the body. It is designed to help the SMN2 gene produce more functional SMN protein that better supports motor neurons and muscle function. In November 2019, the U.S. Food and Drug Administration (FDA) granted Priority Review for risdiplam with a decision for approval expected by May 24, 2020. As requested by the FDA in February of this year, additional data from the pivotal SUNFISH Part 2 study was

submitted, and due to the volume of data submitted by the company, the FDA extended its New Drug Application (NDA) review to August 24, 2020. The FDA confirmed the extension is not related to any current efficacy or safety concerns of Risdiplam or to the COVID-19 pandemic. AveXis is conducting a long-term, safety follow up study of patients in the AVXS-101-CL-10 (START) gene replacement therapy clinical trial for SMAType 1, delivering onasemnogene abeparvovec-xioi . Patients will roll over from the parent study into this long-term study for continuous safetymonitoring for up to 15 years. This study is expected to be completed in late 2033.

40 |

DIRECTIONS | SPRING 2020

UPDATES