A forthcoming Phase 2 trial could go a long way to determining whether InhaleRx can fill the pharmaceutical void for patients suffering from breakthrough cancer pain. The signs are encouraging.
ASX-listed InhaleRx is striving to “redefine” treatment options for Breakthrough cancer pain (BTcP) as it seeks to fill a pharmaceutical void left by the withdrawal of fentanyl drugs in the US.
A Phase II trial is set to launch in early 2025 exploring the benefits of IRX211, an inhaled synthetic THC formulation, which InhaleRx management believes has the potential to provide rapid onset and predictable pain relief for BTcP patients.

The company uses novel cold-delivery pMDI technology (a non-heated, non-vaped, pressurised metered-dose inhaler) with initial phase I pharmacokinetics data delivering encouraging results.
Breakthrough cancer pain (BTcP) is a sudden and severe pain episode that interrupts the background pain relief provided by long-acting analgesics. It typically occurs without warning, sometimes with no identifiable causes, peaks within minutes and lasts for up to an hour.
Historically, immediate-acting fentanyl-based drugs such as Abstral or Fentora (fentanyl buccal tablets) and Actiq (fentanyl lozenges) were widely used for managing the condition.
But while those treatments provided significant relief over the past two decades, the withdrawal last year due to safety concerns and misuse potential of transmucosal immediate-release fentanyls (TIRFs), has left patients with no approved BTcP-specific therapies.
The withdrawal was largely triggered by FDA-mandated Risk Evaluation and Mitigation (REMs) programs that were imposed on all fast-acting fentanyl therapies. It saw prescription numbers rapidly dwindle and the drugs becoming uneconomical to market.
InhaleRx chief executive Darryl Davies said the need for new medicine was clear.

“In short, there are no current FDA-approved products making a label claim for BTcP on the US market today,” he said: “Breakthrough cancer pain remains one of the biggest unmet needs in the cancer world and it is devastating to think that so many patients can suffer through it without there being any reasonable pharmaceutical solutions.”
Despite the potential harms and fears over their role in the global opioid epidemic, TIRFs are understood to have provided a clear benchmark for evaluating the efficacy threshold for new therapies seeking FDA approval, targeting BTcP, including IRX211.
According to Dr Sud Agarwal, chief executive of iNGENū, a contract research organisation with close ties to InhaleRx, the most common endpoints used by the FDA to approve previous drugs was the Pain Intensity Reduction at 30 minutes, or Sum of Pain Intensity Differences at 30 minutes (SPID₃₀).
For Fentora, a fentanyl buccal tablet, SPID₃₀ was 3.0 compared to 1.8 for placebo, reflecting an improvement of 1.2 points above placebo.
Meanwhile, Actiq, a fentanyl lozenge, achieved a mean pain relief score of 2.5 at 30 minutes compared to 1.0 for placebo, an improvement of 1.5 points above placebo.
“These efficacy results highlight the substantial pain relief these drugs provided,” Dr Agarwal said. “For IRX211 to establish itself as a viable alternative, its pivotal trials should demonstrate similar or greater improvements in pain intensity and relief.

“The trial is designed to rigorously evaluate its efficacy and safety profile, with the hope of providing a much-needed solution for this highly challenging condition.”
Dr Agarwal said the initial phase I pharmacokinetics data was encouraging, with IRX211 achieving similar plasma THC doses without heating, vaping or smoking and with no significant adverse events.
Based on these THC results via a pMDI, it could have the potential to provide comparable or superior efficacy to fentanyl-based drugs, he added.
The risk of dependency and abuse is also greatly reduced, given it is a non-opioid mechanism, using synthetic THC.
While researchers are reluctant to predict or even speculate on the results of clinical trials, Dr Agarwal said IRX211 represents a “promising solution for BTcP” with the potential to provide rapid-onset, tailored pain relief with a safer profile than historical fentanyl-based treatments.
BTcP remains one of the “biggest unmet needs in the cancer world”, he added.
“Breakthrough cancer pain significantly limits patients’ physical abilities, disrupts sleep, and diminishes overall strength, leaving many dependent on caregivers for daily tasks,” Dr Agarwal said. “And beyond its physical toll, it causes severe emotional distress, contributing to anxiety, fear of future episodes, and depression, which can lead to social isolation and a reduced quality of life.
“By aiming to achieve similar or superior efficacy to Abstral, Fentora and Actiq in the pivotal trials, IRX211 has the potential to fill the void left by these withdrawn drugs and provide a much-needed option for cancer patients experiencing breakthrough pain.”