Aligos planning for Phase 2 trial of treatment for hepatitis B
FDA clears launch of drug-drug interaction study
The U.S. Food and Drug Administration (FDA) has cleared the launch of a Phase 1 drug-drug interaction study to evaluate the effects of certain drugs on the pharmacological properties of ALG-000184, Aligos Therapeutics’ oral treatment candidate for hepatitis B.
Aligos said the study will involve sites in the U.S., but didn’t provide details about estimated time of trial initiation or exact locations.
The clearance “allows us to begin the next stages of our clinical development for ALG-000184, including the advancement of the compound into Phase 2 clinical trials,” Lawrence Blatt, PhD, chairman, president, and CEO of Aligos, said in a company press release.
The therapy is already being tested in healthy people and those chronically infected with the hepatitis B virus (HBV) in a Phase 1 clinical trial (NCT04536337) conducted outside the U.S. Preliminary data have indicated ALG-000184 is well tolerated and leads to sustained viral suppression.
“ALG-000184 has demonstrated impressive data to date with broad antiviral activity,” said Hardean Achneck, MD, Aligos’ chief medical officer. “ALG-000184 has the potential to improve outcomes compared to the current standard of care.”
Phase 2 study plans
The company is already preparing for the launch of a Phase 2 study, with plans to file applications with regulatory agencies seeking the treatment’s clearance in the first quarter of 2025.
“We look forward to finalizing the Phase 2 study design in conjunction with [key opinion leaders] and the FDA and anticipate enrolling patients next year,” Achneck said.
In hepatitis B, infection with HBV gives rise to liver inflammation. While hepatitis B often resolves without major problems, some people will go on to develop chronic infections that increase the risk of serious liver damage and liver cancer.
Current treatment for chronic HBV infection includes a class of antiviral therapies called nucleoside/nucleotide analogues, which work to stop the virus from being able to replicate its DNA in the body.
ALG-000184 belongs to a class of therapies called capsid assembly modulators, which essentially interfere with the formation of the capsid, or the shell that surrounds a viruses’ genetic material. Ultimately, the treatment is expected to not only suppress viral DNA, but also the production of important proteins that the virus needs to infect human cells.
By targeting HBV at all points in its life cycle, Aligos expects that ALG-000184 will lead to better suppression of HBV infections than other types of antivirals.
“ALG-000184 is the first novel, oral drug candidate for the treatment of HBV infection that can inhibit multiple components of the viral lifecycle, leading to more complete suppression of the virus compared to other therapeutic modalities,” Blatt said.
Evaluating long-term effects
In the first two parts of the ongoing Phase 1 study, single and multiple doses of ALG-000184 were found to be well tolerated in healthy volunteers.
For its third part, people with chronic HBV infections not on other antivirals received daily ALG-000184 (10-300 mg) or a placebo for about a month. Results showed that the treatment was well tolerated at all doses, and resulted in strong antiviral activity, with the ability to suppress HBV DNA and other protein markers of infection.
The study’s ongoing fourth part is evaluating the long-term effects of ALG-000184 (300 mg) when used alone or in combination with approved antiviral therapy entecavir (sold as Baraclude, with generics available) among chronic hepatitis B patients.
A total of 15 participants were enrolled in China, receiving either treatment regimen for three months. Participants in both groups are receiving the combination therapy for up to 96 weeks (about 1.8 years). At sites elsewhere, 21 patients were enrolled, all of whom are receiving ALG-000184 alone for up to 96 weeks.
All participants enrolled in China and half of those enrolled elsewhere were positive for HBeAg, an HBV protein that signals that the virus is actively replicating in the body.
Results from up to 1.5 years of treatment showed that ALG-000184 led to “best-in-class” reductions in relevant viral markers, reflecting the treatments’ ability to disrupt HBV at all points in its life cycle, according to Aligos.
The ALG-000184-entecavir combo led to greater reductions in viral load than entecavir alone, and ALG-000184 was similarly effective regardless of whether it was used with entecavir. The virus remained consistently suppressed the entire time, both for patients positive and negative for HBeAg.
Dosing through 96 weeks is ongoing, Aligos said. The company plans to report additional trial data at upcoming scientific conferences, it said.
The drug-drug interaction study will evaluate the effect of drugs that influence the activity of cytochrome P450, a key enzyme for the metabolism of many medications, in ALG-000184’s movement into, through, and out of the body.
Should it be approved by regulatory bodies, the Phase 2 trial will test ALG-000184 against standard-of-care antiviral therapies in people with chronic hepatitis B with and without for HBeAg.
The main goal will be to assess the proportion of patients showing very low levels of HBV DNA after about one year. Secondary goals will include the proportion of HBeAg-positive patients who become negative for that marker, and changes in these and other HBV DNA, RNA, and protein biomarkers.
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