Intellia Therapeutics has dosed the first patient in a pivotal trial of its in vivo clustered regularly interspaced short palindromic repeat (CRISPR) candidate NTLA-2001.
The US-based biotech has begun dosing in the global, Phase III study with its one-time gene editing treatment for patients with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
The in vivo CRISPR-Cas9 candidate acts by inactivating the transthyretin (TTR) gene to prevent the production of the TTR protein, which causes the disease.
The MAGNITUDE trial (NCT06128629) will be a randomised, double-blind, placebo-controlled study evaluating the efficacy and safety of NTLA-2001 in 765 patients. Patients will be randomised on a 2:1 ratio to receive a single 55mg infusion of the candidate or a placebo.
The first patient was dosed at Richmond Pharmacology in the UK. The trial will take place across three other sites, notably two in New Zealand and one in the US.
The primary endpoint of the study is cardiovascular (CV) mortality and CV-related events at 18 months. Secondary endpoints will evaluate change in serum TTR and change in Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OS) at 18 months.
Intellia Therapeutics has partnered with Regeneron for the development of NTLA-2001.
GlobalData’s annual consensus forecast for NTLA-2001 projects that sales will reach $1.4bn in 2029.
GlobalData is the parent company of the Clinical Trials Arena.
CRISPR landscape
December 2023 marked an important moment in the history of CRISPR therapies after Vertex Pharmaceuticals’ and CRISPR Therapeutics’ exagamglogene autotemcel (exa-cel) was the first CRISPR-based therapy to receive approval from the US Food and Drug Administration (FDA).
The landscape is still evolving with many companies at discovery and pre-clinical stages. There are some candidates in clinical trials but 88% of them are in the early stages.
Several CRISPR candidates are further ahead in the pipeline, including Vor BioPharma’s VOR33, Shanghai Vitalgen BioPharma’s VGB-Ex01 and EdiGene ET-02.
Although expected to be one of the greatest pharmaceutical advances of the decade, there are potential risks and challenges associated with CRISPR gene editing including ethical and practical difficulties in conducting trials, concerns about safety and long-term adverse events of CRISPR therapies, potential off-target effects, and unintended modifications.
In 2020, the Royal Swedish Academy of Sciences awarded the Nobel Prize in Chemistry to two leading CRISPR researchers, Jennifer Doudna and Emmanuelle Charpentier.
