NEW YORK (GenomeWeb) – After teasing its return to the kind of big indications that once populated its pipeline, Alnylam Pharmaceuticals last week disclosed that it has early-stage efforts underway in non-alcoholic steatohepatitis (NASH) and type II diabetes — two liver diseases that affect millions of patients.
Speaking during a webcast research and development meeting with financial analysts, company officials noted that the programs are largely driven by a greater understanding of human genetics and advances made with the company's liver-targeting GalNAc subcutaneous delivery conjugates.
"There is robust new human genetics [that] is allowing us to think more about targets that are going to be important, as well as think about how we segment patient populations," Rachel Meyers, vice president of research and RNAi lead development at Alnylam, said during the event.
Meanwhile, with ever-increasing safety data on the GalNAc technology, "we can actually think about moving past rare disease and we can start thinking about accessing larger disease populations where we can have an impact in millions of patients potentially."
Company officials did not provide additional details about the programs during the presentation.
When Alnylam was founded in 2002, it set its sights on major diseases such as influenza, age-related macular degeneration cancer, respiratory syncytial virus, and Parkinson's disease. Yet none of these programs have advanced beyond Phase II, either due to technical limitations or changes in the competitive landscape.
In 2011, Alnylam announced a new strategy wherein it would focus on drug candidates against "genetically defined targets and disease … [with the] potential to have a major impact in a high unmet need population."
The result has been a growing pipeline of potential treatments for rare diseases including transthyretin-mediated amyloidosis (ATTR), hemophilia, complement-mediated disorders, porphyria, preeclampsia, beta-thalassemia, and alpha-1 antitrypsin deficiency. Notably, both of Alnylam's ATTR drugs — patisiran, which is delivered using lipid nanoparticles, and revusiran, which is GalNAc-enabled — are in Phase III.
Amid these advances, and bolstered by a sweeping, $700 million tie-up with Genzyme, Alnylam has slowly been testing the waters of bigger indications, although always with a focus on the liver where delivery is less challenging than with other organs or tissues.
Earlier this year, Alnylam announced that it had added to its pipeline a hepatitis B program, which it acquired when it bought the RNAi assets of Merck. The company has also been collaborating with The Medicines Company to push ahead a subcutaneously administered version of its hypercholesterolemia candidate ALN-PCS that uses GalNAc conjugates instead of the lipid nanoparticles of its predecessor.
The HBV treatment is expected to enter Phase I testing in 2015, while a Phase I study of the cholesterol drug kicked off earlier this month.
Both of these programs "represent the beginning of a strategy outside of the rare disease space," Alnylam Chief Business Officer Laurence Reid said in October during the Leerink Partners Rare Disease Roundtable.
The next steps, it seems, include NASH and diabetes.
Steatohepatitis is characterized by inflammation, fat accumulation, and scarring in the liver. Often caused by chronic alcohol abuse, it is also found in non-alcoholics who have diabetes, or are obese or insulin resistant.
According to Alnylam, roughly 1 million patients in the US are diagnosed with NASH annually, and the condition is the third most common cause of liver transplantation. There are no approved therapies.
When it comes to developing an RNAi treatment for NASH, "human genetics is really going to be our friend here and is going to guide us toward incredibly important targets that are expressed in the liver," Meyers said.
Additionally, Alnylam sees the potential for a combination approach to treating the disease, identifying multiple drug targets that affect different pathways and then combining them, she said.
As for type II diabetes, Meyers noted that the disease is one of the fastest growing health burdens and is expected to affect as many as 370 million people globally by 2030.
"Human genetics here again is going to guide the way … to identify important liver-expressed targets … [and] again, we can think about combination strategies," she said. Alnylam is aiming to develop a therapy that can provide a dual benefit to patients, such as glucose control in addition to weight loss.
Alnylam did not provide a timetable for when it might begin clinical testing of NASH or type II diabetes candidates, but indicated that Phase I studies could begin in 2017 or 2018.