Arrowhead Pharmaceuticals’ “gene-silencing drug” candidate for a fatty liver disease, non-alcoholic steatohepatitis (NASH), is ready for the next phase of clinical testing, and GlaxoSmithKline will take this step in its hands.The pharmaceutical giant has agreed US$120 million in advance Fight for Arrowhead’s right to treat drug candidates and bet that its approach to new disease targets can stand out in the field of drug research that has suffered numerous setbacks.
The transaction was announced after the close on Monday, granting GlaxoSmithKline the right to develop and commercialize Arrowhead’s drug ARO-HSD. These exclusive rights are spread all over the world, except for China, where Arrowhead reserves its rights. Milestone payments may bring up to $910 million in benefits to biotechnology, which is a considerable advantage and represents the scale of treatment opportunities.
NASH is a fatty liver disease that has become increasingly popular with poor eating habits. It has no FDA-approved treatment. Fat accumulation can lead to scarring of the liver; in the most severe cases, the patient must receive an organ transplant.according to American Liver Foundation, NASH is the most common chronic liver disease in the United States, affecting approximately 25% of adults in the country.
The drug development headquartered in Pasadena, California is based on RNA interference (RNAi), a type of therapy made from small interfering RNA. These drugs prevent genes from producing the RNA needed for disease-causing proteins. This method is sometimes called gene silencing. Alnylam Pharmaceuticals won FDA approves RNAi drugs for the first time in 2018, To treat nerve pain caused by rare genetic diseases. Arrowhead’s NASH drug ARO-HSD targets HSD17B13, an enzyme involved in the metabolism of hormones, fatty acids, and bile acids. Studies have shown that stopping this enzyme can prevent liver disease, including NASH.
At the annual meeting of the American Association for the Study of Liver Diseases held earlier this month, Arrowhead Phase 1 data of the report Shows that its drug causes a decrease in messenger RNA and HSD17B13. The reduction is dose-dependent, and at the highest of the three doses, the reduction in mRNA is greater than 90%. The level of HSD17B13 was reduced at all doses, and the drug caused a reduction in two key liver enzymes at medium and high doses. The patient tolerated Arrowhead therapy well and no serious adverse events were reported.
In a prepared statement, John Lepore, head of research at GlaxoSmithKline, stated that the evidence linking HSD17B13 variants to protecting the liver from inflammation suggests that Arrowhead drugs have a chance to become a first-class treatment for NASH. Arrowhead CEO Chris Anzalone stated on the conference call that the transaction with GlaxoSmithKline allowed Arrowhead to use the funds it had originally used to develop ARO-HSD for the possible commercialization of the biotechnology.
GSK is Arrowhead’s second NASH partner. Johnson & Johnson subsidiary Janssen is developing a NASH drug candidate developed using Arrowhead’s RNAi technology. The drug JNJ-75220795 is designed to reduce the expression of PNPLA3, which is a different liver enzyme with preclinical verification that drives liver fat accumulation and damage. The Janssen drug is currently in the first phase of testing.
Although the unmet medical needs in NASH are attractive to drug developers, there have been several notable mistakes in the field. Gilead Sciences’ NASH drug candidates failed to pass Phase 3 studies in 2019. last year, Genfit’s NASH drug candidate failed key test. After that setback FDA rejects Intercept Pharmaceuticals drug This was once regarded as the front runner of the first approved NASH therapy. Last year, a clinical trial of a Cymabay Therapeutics NASH drug candidate was cleared. But when Cymabay Resumption of clinical trials, the company did not continue in NASH And chose to continue testing the drug in rare liver diseases.
These setbacks did not stop the company from developing NASH drugs. Gilead is still working with Novo Nordisk to test treatments for this diseaseOther companies with mid-to-late NASH drug candidates include Madrigal Pharmaceuticals, Viking Therapeutics, Akero and 89Bio. According to Anzalone, Arrowhead’s NASH drug collaboration process is competitive. Although he did not provide details, he said that the ongoing NASH alliance between Johnson & Johnson and Arrowhead did not give it any priority to obtain ARO-HSD​​.
“We talked to multiple companies about this asset, and GlaxoSmithKline seems to be the best partner,” Anzalon said. “Johnson & Johnson has no right of first refusal or similar rights [ARO-HSD]. “
Arrowhead has established multiple partnerships with major companies in a range of therapeutic areas. In addition to NASH, the Johnson Alliance also includes chronic hepatitis B virus infection. Amgen is developing an Arrowhead RNAi therapy for cardiovascular disease. last year, Takeda Pharmaceutical paid 300 million US dollars in advance to start cooperation on Arrowhead A medicine to treat rare liver diseases. And earlier this year, Horizon has paid US$40 million in advance to obtain the right to develop Arrowhead RNAi therapy for gout.
The Arrowhead/GSK deal was announced last week Novo Nordisk will acquire Dicerna Pharma, its RNAi research and development partner, for USD 3.3 billionAnzalone said that Arrowhead has not seen an increase in partner interest recently, adding that recent acquisitions in this area will not affect the daily business of biotech companies.
“Our job is to make drugs that are safe and can help patients in ways that other drugs cannot help,” Anzalone said. “As long as we can focus on this, we can succeed in this area, and we can do it quickly, and everything else will follow.”
Photo by GlaxoSmithKline
