Dicerna Plans to Launch RNAi Clinical Trial in Liver Disease

Dicerna Pharmaceuticals, headquartered in Cambridge, Massachusetts, announced it has submitted a Clinical Trial Authorization (CTA) application to the Swedish Medical Products Agency (MPA). The goal is to receive approval to launch a first-in-human Phase I/II clinical trial of DCR-A1AT for the treatment of alpha-1 antitrypsin (A1AT) deficiency-associated liver disease.

Dicerna focuses on what is called RNA interference or RNAi. The technology turns off RNA, which results in halting the production of disease-causing proteins.

In 2016 the company abandoned its first cancer drug after underwhelming data from two early-stage clinical trials. That technology was a lipid nanoparticle, DCR-MYC, which was evaluated in two Phase I trials in patients with solid tumors, hematological cancers and pancreatic neuroendocrine tumors, and another in patients with hepatocellular carcinomas. Their research showed that the nanoparticle worked as a drug delivery system, but the therapy itself wasn’t as effective as hoped, so it pivoted to focus on its GalXC technology platform.

The new therapy it's seeking approval for utilizes the GalXC technology.

A1AT deficiency is a genetic disorder that can lead to liver disease in children and adults. Complications to the disease can be weight loss, fatigue, jaundice and life-threatening cirrhosis. They are also at risk of hepatocellular carcinoma.

“We are pleased to begin the clinical development phase of our A1AT deficiency-associated liver disease program, which serves two roles in Dicerna’s portfolio,” stated Douglas Fambrough, president and chief executive officer of Dicerna. “First, A1AT deficiency-associated liver disease fits with our rare disease strategy as an indication with a significant unmet medical need and a clear biomarker, presenting a rapid development path to approval.”

“Second,” Fambrough continued, “the program will inform and aid our efforts in the much broader chronic liver disease field, where we believe our GalXC platform can have a major impact, and which provides ample opportunities to collaborate with larger pharmaceutical company partners.”

The proposed clinical trial would evaluate DRC-A1AT in healthy adults and patients with A1AT deficiency-associated liver disease and would have two parts. Group A would be a single ascending-dose phase in healthy volunteers and enroll up to 36 participants in as many as six cohorts. Group B would be a multiple ascending-dose phase in patients with A1AT deficiency-associated liver disease and be made up of 24 participants in three or fewer cohorts.

If the Swedish MPA approves, the company hopes to launch screening of healthy volunteers for Group A in the third quarter of this year and start enrolling Group B patients in the first quarter of 2020. It hopes to have up to 16 sites in Europe, with the first in Sweden.

Dicerna does much of the research and discovery work but usually enters partnership arrangements for much of the development work. So far, it has signed development deals with Alexion Pharmaceuticals, Eli Lilly and Boehringer Ingelheim. The company indicates it is currently looking for a partner to commercialize a Hepatitis B drug it is developing. It doesn’t plan to partner on the new liver drug candidate.

“The launch of the DCR-A1AT clinical program is welcome news to the A1AT deficiency community, as there are currently no approved therapies that treat the liver manifestations of this condition,” stated Miriam O’Day, president and chief executive officer of the Alpha-1 Foundation. “We look forward to working with Dicerna as they advance DCR-A1AT through clinical trials.”