Pasadena-based Arrowhead Pharmaceuticals Inc. in recent weeks has notched significant progress with clinical trials of drugs developed from its platform that turns off genes that can trigger diseases.

On June 24, Arrowhead presented what it termed “promising” updated results of a Phase 2 clinical study of a drug for treatment of a specific type of liver disease.

Then, three days later, Arrowhead announced it had filed an application with the Food and Drug Administration to begin clinical trials of its first drug that directly targets the body’s central nervous system – in this case to treat patients with amyotrophic lateral sclerosis (ALS, more commonly known as Lou Gehrig’s disease after the famous ballplayer who contracted it) caused by a specific set of genetic mutations.

Arrowhead’s liver-disease drug, which it calls fazirsiran, targets a subset of the disease associated with a deficiency of alpha-1 antitrypsin, which protects the body from the over-production of an infection-fighting enzyme called neutrophil elastase. Essentially, alpha-1 antitrypsin prevents this immune-system enzyme from going into overdrive. But some patients develop a mutant non-functional strain of alpha-1 antitrypsin that can accumulate in the liver and cause damage on its own. It is this mustant strain that fazirsiran targets.

The company released updated results from a Phase 2 clinical study of this fazirsiran drug at a recent European conference focused on liver diseases and their treatment. According to Arrowhead, the results were similar to another ongoing Phase 2 study of the drug, demonstrating significant reductions of the mutant strain of alpha-1 antitrypsin, which in turn resulted in a reduction of common symptoms associated with liver disease.

“The clinical results from the Phase 2 Sequoia study of fazirsiran were clear and compelling,” Javier San Martin, Arrowhead’s chief medical officer, said in a statement on the clinical trial results. “Fazirsiran treatment demonstrated a substantial effect on several key markers of liver disease.”

San Martin said Arrowhead is in the midst of a Phase 3 clinical trial – generally the last and most extensive clinical trial phase before a drug is submitted to the FDA for approval – of fazirsiran. That trial involving 160 patients is being conducted jointly with Tokyo-based Takeda Pharmaceutical Co., which has a licensing partnership with Arrowhead.

While clinical trials are nearing their conclusion for fazirsiran, Arrowhead is hoping it can soon begin clinical trials for its new – as yet unnamed – drug targeting the central nervous system. This drug is designed to reduce the expression of a gene known as superoxide dismutase 1 in the central nervous system. Around the turn of this century, this gene – or more accurately a mutated version of this gene –was the first one directly linked to ALS.

Pending regulatory clearance, Arrowhead intends to proceed with a randomized, placebo-controlled dose escalation Phase 1 study to evaluate the safety, tolerability and drug transmission mechanics of its drug, which has been given the placeholder name of ARO-SOD1. The clinical trial is expected to enroll as many as 24 subjects.

“The ARO-SOD1 program entering clinical studies represents the further expansion of our proprietary TRiM platform, which now includes product candidates addressing a multitude of diverse disease areas that target the liver, lung, muscle, and central nervous system,” Chris Anzalone, Arrowhead’s chief executive, said in the announcement. 

TRiM is the name Arrowhead has given to its platform that uses RNA interference technology to regulate the activation of genes that can cause a wide range of diseases. This is done by using small pieces of RNA to inhibit the production of proteins that activate the genes.

Neither of these clinical trial announcements prompted significant movement of Arrowhead’s stock, which has mostly traded in a narrow range between $35 to $37 a share since the beginning of June.