An Arrowhead Pharmaceuticals drug for a rare liver disease now has early Phase 2 results and the data so far look good. Not only did the therapy reduce levels of a mutant protein associated with the disorder, but patients also showed improvements in several biological measures of liver injury.
The results are for just four patients from a small 16-patient study testing the drug, ARO-AAT, as a treatment for liver disease associated with alpha-1 antitrypsin deficiency. But the early results are an encouraging sign for Arrowhead (NASDASQ: ARWR) and its approach to treating inherited diseases by stopping genes from producing the problem proteins at the root of these conditions.
Arrowhead’s stock price soared as high as $50.39 in Wednesday morning trading, up more than 51 percent from Tuesday’s close.
Arrowhead, which is based in Pasadena, CA, and houses its research operations in Madision, WI, develops drugs that harness RNA interference, a biological mechanism cells use to stop a gene from producing a disease-causing protein. Alpha-1 antitrypsin deficiency is an inherited disorder leading to low levels of the protein that gives the disease its name. That deficiency can lead to lung and liver disease, according to the National Organization for Rare Disorders (NORD). While there are treatments for the lung problems associated with this protein deficiency, there are no specific liver therapies, NORD says.
The Arrowhead drug is intended to silence the gene that produces a mutant version of the alpha-1 antitrypsin protein, preventing its accumulation in the liver. In doing so, the company says the organ can then clear the accumulated mutant protein and prevent repeated cycles of cellular damage. It’s hoped that the drug can prevent or even reverse the progression of liver fibrosis.
Arrowhead isn’t the only company testing an RNAi drug for alpha-1 antitrypsin deficiency. Boston-area companies Dicerna Pharmaceuticals (NASDAQ: DRNA) and Alnylam Pharmaceuticals (NASDAQ: ALNY) have clinical-stage therapies in their respective pipelines, and earlier this year they struck up cross-license agreement for the development and potential commercialization of their RNAi drugs for the disease.
Arrowhead is testing its injectable alpha-1 antitrypsin deficiency drug in two separate studies. The first, a placebo-controlled Phase 2/3 clinical trial enrolling approximately 120 patients, is intended to be a pivotal study with the potential of supporting a filing seeking FDA approval. The results released Wednesday were for an open-label Phase 2 study assessing changes in the liver over time. According to those results, after 24 weeks, levels of the mutant protein in the blood were reduced by up to 93 percent in the four patients; levels of the mutant protein in the liver were reduced by up to 95 percent. Arrowhead also reported additional data showing that fibroris, or liver scarring, improved by up to 26 percent and the biological signs of liver injury were reduced by up to 66 percent.
The results disclosed were the best single patient for each metric, SVB Leerink analyst Mani Foroohar wrote in a Wednesday note to investors. But he added that those results look robust, and they suggest the drug could modify the disease and help patients as long the clinical measures are shown to be related to the knockdown of the mutant protein.
Arrowhead has submitted a late-breaker abstract for presentation at the American Association for the Study of Liver Disease meeting in November. If accepted, the company plans to report additional data at the meeting. Foroohar wrote in his research note that additional liver biopsies are expected every six months up to the 24 month mark. Those results will inform the goals of the pivotal Phase 2/3 study and the regulatory path forward for the Arrowhead drug.
In a prepared statement, Arrowhead Chief Medical Officer Javier San Martin said that the company expected that six months of treatment would lead to substantial reductions in the mutant protein. But the improvements in the biological indicators of liver injury “were more substantial than we expected,” he said. San Martin added that the company plans to talk with the FDA to identify ways that the program could be streamlined or accelerated.
ARO-AAT is Arrowhead’s most advanced wholly owned drug candidate. The company licensed its hepatitis B program to Janssen, a Johnson & Johnson (NYSE: JNJ) subsidiary; a cardiovascular disease program is in development under a partnership with Amgen (NASDAQ: AMGN).
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