IPL344 is an experimental treatment for amyotrophic lateral sclerosis (ALS) that is being developed by Immunity Pharma to slow disease progression.
How does IPL344 work?
ALS is a progressive disease of the nervous system characterized by the death of motor neurons — nerve cells that control voluntary muscles. The disease affects both upper motor neurons in the brain and lower motor neurons in the spinal cord and brainstem. The loss of upper motor neurons leads to symptoms such as muscle tightness (spasticity), while the loss of lower motor neurons results in twitching, the shrinking of muscles (atrophy), and muscle weakness.
IPL344 is a molecule that researchers designed to activate the Akt signaling pathway, which plays a role in the survival of cells. That pathway inhibits apoptosis, or naturally programmed cell death, and blocks inflammation in cells. Studies have shown that the activity of the Akt pathway is reduced in patients with ALS. By activating that pathway, researchers think that IPL344 may help protect nerve cells and slow the progression of the disease.
IPL344 in clinical trials
Researchers are currently investigating IPL344 in an open-label Phase 1/2a clinical trial (NCT03652805). The study aims to recruit 15 adults with ALS in Israel to receive intravenous (IV; into-the-vein) injections of IPL344. In the Phase 1 portion, participants are given increasing daily doses of IPL344 for 28 days. Patients start with a dose of 1.7 mg/kg of body weight and increase by 0.5 mg/kg every three to four days, up to a maximum dose of 3.2 mg/kg.
The goals for this phase of the trial are to assess the therapy’s safety, tolerability, and pharmacokinetics (movement in the body), and to determine the maximum tolerated dose of the treatment.
After the 28 days, the investigators may offer patients the option to continue receiving treatment for up to three years during the Phase 2 portion of the trial (NCT03755167). This follow-up portion is designed to continue to monitor the safety and tolerability of the treatment, as well as evaluate its initial efficacy.
Interim results from the study showed that eight participants completed the initial 28-day portion of the study without any treatment-related side effects.
Six patients had completed between four and 13 months of treatment, with an average of eight months. They showed a decrease in their functional decline compared with the period prior to starting treatment, based on measures of their functional ability using the ALS Functional Rating Scale-Revised (ALSFS-R). Based on the period before treatment (average of six months), the patients’ scores declined an average of 4.7 points, which was fewer than projected.
The researchers also reported a slowing in the decline of slow vital capacity (SVC), a measurement of lung function that determines how much air a person can expel slowly. Patients lost 1.3% of their SVC per month on average. Meanwhile, the average loss in the general ALS population is 3.1% per month. The interim results also showed that IPL344 restored Akt activation values to normal levels.
Following these encouraging results, Immunity Pharma is planning a placebo-controlled Phase 2 trial in the future to further investigate the treatment. The current trial continues to recruit patients; researchers expect it to conclude in August 2022.
The U.S. Food and Drug Administration and the European Medicines Agency both granted IPL344 orphan drug designation in early 2020. That status provides incentives for pharmaceutical companies to develop treatments for serious rare diseases that affect fewer than 200,000 people in the U.S and 5-in-10,000 in Europe. It provides 10 years of protection against competing sales of the same drug in Europe and seven years in the U.S. In Europe, it also guarantees a centralized regulatory process.
Last updated: Dec. 9, 2020
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