Currently, there are no treatments available for patients with hereditary ATTR amyloidosis (hATTR); most available therapies are designed to aid with symptom management. However, biotechnology company and RNA-targeted therapeutics leader Ionis Pharmaceuticals, Inc. (“Ionis”) is working to address this unmet need through eplontersen. According to a press release shared by AP News, enrollment is now complete in the Phase 3 NEURO-TTRansform clinical trial evaluating eplontersen for patients with hATTR and hATTR-related polyneuropathy.
So what exactly is eplontersen? According to Ionis, eplontersen is:
a ligand-conjugated (LICA) investigational antisense medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of TTR amyloidosis (ATTR), a systemic, progressive and fatal disease. In patients with ATTR, both the mutant and wild type TTR protein builds up as fibrils in tissues…[and] interferes with the normal functions of these tissues.
Thus, to prevent tissue damage and a worsening quality of life (QOL), eplontersen is designed to stop TTR protein accumulation. In prior studies, the treatment inhibited TTR production by up to 94%, showing extreme efficacy.
Thus far, a large amount of patients have enrolled in the Phase 3 NEURO-TTRansform trial. In fact, Ionis even went over its target for trial enrollment. Altogether, over 160 patients are expected to enroll – and be dosed – within this trial. During the trial, researchers seek to understand the safety, efficacy, and tolerability of eplontersen in patients with hATTR-related polyneuropathy. Learn more about polyneuropathy, caused by peripheral nerve damage.
Patients enrolled in the trial have either Stage 1 or 2 polyneuropathy. Altogether, the trial will run for around 66 weeks, with a follow-up period of 85 weeks. Researchers will evaluate the drug’s efficacy through a change in serum TTR concentrations, as well as changes in scores using mNIS+7 and Norfolk QoL-DN.
Hereditary ATTR Amyloidosis (hATTR)
TTR gene mutations cause hereditary ATTR amyloidosis (hATTR). This is considered the familial subtype of amyloidosis, a disease in which abnormal proteins (amyloids) accumulate in organs and tissues, causing a variety of issues. In patients with hATTR amyloidosis, this most often affects the heart and nervous system. hATTR amyloidosis may appear as familial amyloid cardiomyopathy, senile systemic amyloidosis, or familial amyloid polyneuropathy.
Symptoms depend on which organs or tissues are affected by abnormal amyloids. For example, if the heart is affected, symptoms may include:
- Unintended weight loss
- Shortness of breath
- Worsening fatigue
- Swelling of the lower extremities
- Chest pain
- Atrial fibrillation
If the nervous system is affected, patients may experience:
- Autonomic or peripheral neuropathy
- Sensorimotor impairment
Alternately, symptoms associated with digestive system function include:
- Nausea and vomiting
- Diarrhea or constipation
- Difficulty maintaining bladder control
- Appetite loss
- Feeling of “fullness,” even without eating a lot
- Unintended weight loss