Alexion Adds More Complement System Targets to Dicerna’s RNAi-based Therapy Collaboration

Alexion Pharmaceuticals now holds exclusive rights to Dicerna’s potential RNA interference (RNAi) therapies developed against four targets of the complement system, which plays a role in many diseases, including atypical hemolytic uremic syndrome (aHUS).

aHUS results from an abnormal activation of the complement system, a set of more than 50 blood proteins mainly produced by the liver that contribute to the body’s natural immune defenses.

Alexion’s Soliris (eculizumab) and Ultomiris (ravulizumab-cwvz) are two monoclonal antibodies approved by the U.S. Food and Drug Administration for treating aHUS. They both specifically target protein C5 of the complement system and have been shown to effectively prevent or reduce complement overactivation and associated damage in aHUS patients.

Aiming to expand its portfolio of complement-directed therapies, Alexion initiated a collaboration with Dicerna, a leading developer of investigational RNAi therapies, in 2018.

RNAi is a natural process of gene silencing in which small interfering RNA (siRNA) molecules regulate the expression of genes. siRNA binds to a specific messenger RNA (mRNA) — the molecule generated from DNA that guides the production of a specific protein — targeting it for destruction, ultimately preventing production of that protein.

Since specific siRNA molecules can be designed for any gene of interest, and a single siRNA molecule is able to silence many target mRNAs, RNAi therapy has the potential to prevent or reverse complement over-activation in people with complement-associated diseases, including aHUS.

Dicerna’s RNAi technology platform, called GalXC, was designed to develop next-generation, optimized RNAi-based therapies that prevent the production of specific proteins in the liver.

The initial goal of Alexion and Dicerna collaboration was to identify and develop subcutaneous (delivered under the skin) RNAi-based therapies targeting two complement molecules for the treatment of complement-associated diseases.

Now, Alexion has exerted its option to include two additional complement targets in its agreement with Dicerna, associated with a total $20 million payment.

“With more than 20 years of experience, Alexion is a clear leader in the field of complement biology, and we are very pleased by our collaboration’s success to date in identifying potential new GalXC RNAi-based therapeutic approaches to treating complement-related diseases,” Douglas M. Fambrough, PhD, Dicerna’s president and CEO, said in a press release.

“We are encouraged by the collaboration’s progress and the strong relationship our teams have developed over the past year, and we are pleased to expand our efforts to include additional targets in the complement pathway,” said John Orloff, MD, Alexion’s executive vice president and head of research and development.

While Dicerna is leading the discovery and development of these potential therapies in the preclinical stage, Alexion will lead their development through the clinical phase, with exclusive worldwide licensing and commercial rights.

“Our collaboration with Dicerna to discover and develop GalXC RNAi therapies, which have the potential to [suppress] uncontrolled activation of the complement system in new ways, represents an exciting opportunity for Alexion to expand its leadership in developing new medicines for complement-mediated diseases,” Orloff said.

“Alexion’s decision to exercise its option, along with our other new collaborations in different therapeutic areas, underscores the growing recognition of the significant potential for RNAi therapies as a new modality in the treatment of a broad range of diseases,” Fambrough added.