Island backs ISLA-101 dengue potential with top-line Phase 2a/b data

Island Pharmaceuticals says Phase 2a/b top-line results advocate for continued clinical development of ISLA-101 to treat dengue virus.

Island receives top-line results of Phase 2a/b trial of ISLA-101 in dengue virus. Pic via Getty.

• Island Pharmaceuticals says Phase 2a/b top-line results advocate for continued clinical development of ISLA-101 in dengue virus

• ISLA-101 associated with meaningful reduction in viral load and symptoms in preventative cohort

• Company says treatment cohort demonstrated signals of drug effect with investigations ongoing

 

Special Report:  Antiviral drug development company Island Pharmaceuticals is forging ahead after reporting top-line results from its Phase 2a/b PROTECT Trial using ISLA-101 in a human challenge model of dengue virus infection.

Island Pharmaceuticals (ASX:ILA) said initial reviews showed that ISLA-101 was associated with a reduction in viremia (viral load) and a clinically meaningful reduction in symptoms in the preventative cohort.

ISLA-101 was also associated with tangible drug effects in the treatment cohort.

Island’s Phase 2a/b PROTECT trial comprised two patient cohorts:

• Phase 2a evaluated ISLA-101’s ability to prevent dengue fever in four subjects, randomised 3:1 (active: placebo).
• Phase 2b involved 10 subjects, randomised 8:2 (active: placebo), and assessed whether ISLA-101 could reduce viral load and symptoms in individuals already infected with the dengue challenge virus.

Subjects receiving the active treatment in both cohorts were dosed at 600 mg/m²/day.

The challenge virus was provided by the US Army under a Cooperative Research and Development Agreement (CRADA) with support from the Walter Reed Army Institute of Research (WRAIR).

This strain is weaker than wild type dengue, yet subjects are infected with replicating virus and experience mild to moderate dengue symptoms.

The trial was conducted at the State University of New York (SUNY) Upstate in Syracuse, New York, using the SUNY Dengue Human Infection Model (DHIM), which produces measurable viral load and symptoms.

Island said ISLA-101 was the first small molecule tested in this model to show potential benefit.

Watch: Safeguarding against dengue fever

Phase 2a dosed group less sick than placebo

The Phase 2a cohort received ISLA-101 or placebo three days before being inoculated with dengue, to investigate whether the drug can reduce or prevent viral load and dengue symptoms compared to placebo control.

Island said ISLA-101 demonstrated clinically meaningful anti-dengue activity, including a material reduction in viral load and symptoms.

The company said the three subjects treated with ISLA-101 exhibited a clear reduction in virus level.

The dosed subjects also exhibited a clinically meaningful reduction in symptoms compared to control.

When evaluating the maximum possible number of recorded symptoms:

• The control reported ~63% of all potential symptoms; and
• The ISLA-101 pre-treated subjects reported ~33% of all possible symptoms.

Island said the results highlighted ISLA-101’s potential as a preventative measure in dengue, leaving dosed patients less sick than those receiving placebo.

Source: Island Pharmaceuticals

ISLA-101 impacts viral replication in Phase 2b; further study underway

Island said the Phase 2b cohort were inoculated with dengue before being administered either ISLA-101 or seven days after virus exposure.

The company said the primary endpoint was to assess viral load in subjects and based on the preliminary review ISLA-101 impacted viral replication.

Island said because some subjects already had the virus in their blood and symptoms at time of first dosing “alterations in symptoms were less pronounced and are being investigated further”.

“Initial findings highly encouraging”

Following receipt of initial unblinded results, Island said it had undertaken an in-person meeting with its clinical advisory board to review the data and obtain guidance on recommended subsequent actions for clinical development of ISLA-101.

The company said it would continue to work with its advisory board to gain a better understanding of the data, which would determine the potential course of action.

“We are very excited to share top-line results from our successful Phase 2a/b PROTECT study, which show clear anti-dengue activity in humans,” CEO and managing director Dr David Foster said.

“Despite being in a small number of subjects, initial findings are highly encouraging and advocate for continued development of ISLA-101.”

He said the company was pleased to advance the pre-clinical work from Monash and Harvard universities to further highlight the potential for ISLA-101.

“We are confident that additional data will provide a clear determination for the next steps in our clinical trial pipeline and look forward to sharing this as it materialises,” he said.

Chairman Phil Lynch said the ISLA-101 results built positively on the drug's historical assessment and supported consulting with its clinical advisory board to determine the most optimal and economical means of progressing clinical plans.

“Dengue remains a large and growing unmet healthcare need – our ability to address that meaningfully would be well received by patients and the medical community and remains a significant commercial opportunity,” he said.

Scientific advisory board member Professor Stephen Thomas said dengue human challenge studies were complex to execute but could provide a wealth of information about candidate countermeasures early in their development.

“Our collaboration was fortunate to be able to consolidate resources from Island, Upstate Medical University, WRAIR and the US CDMRP to support this study and we are pleased the challenge was successful and performed as expected,” he said.

Dengue fever is the most prevalent mosquito-borne viral disease and, according to the World Health Organization, its incidence has grown dramatically around the world in recent decades.

“The dengue problem is worsening and the number of candidate countermeasures in clinical testing does not align with the global scope of the problem,” he said.

“For this reason, we are very excited Island’s candidate compound demonstrated evidence of antiviral activity against a rigorous dengue human infection model.

“These results set the stage for continued clinical development.”

This article was developed in collaboration with Island Pharmaceuticals,  a Stockhead advertiser at the time of publishing.

This article does not constitute financial product advice. You should consider obtaining independent advice before making any financial decisions.

Originally published as Island backs ISLA-101 dengue potential with top-line Phase 2a/b data