Trial launched to test DISC-3405 for easing iron overload in SCD
Injection therapy to be assessed at 3 doses in 24 adults with sickle cell
Disc Medicine has launched a small clinical trial to test DISC-3405, its treatment candidate for reducing iron levels and easing iron overload, in people with sickle cell disease (SCD).
The Phase 1b trial (NCT07187973) is expected to recruit 24 adults with SCD, who will receive the therapy at up to three dose levels, via subcutaneous, or under-the-skin, injection. Initial data from the trial are expected in 2026, according to the developer.
“We expect new data from … studies of DISC-3405 in … SCD next year,” John Quisel, PhD, CEO and president of Disc, said in a company press release that provided a business update alongside third-quarter financial results.
“With a strong balance sheet … we are well-positioned … [in] advancing [toward] our goal of delivering new treatment options to patients suffering from hematological diseases,” Quisel said.
The company did not provide any data on where the study is being conducted. Eligible participants must be 18 or older, and have experienced SCD-related complications within the last year.
SCD is caused by gene mutations that result in the production of a faulty version of hemoglobin — the protein that carries oxygen in red blood cells — that makes red blood cells acquire a sickle-like shape.
Sickled cells tend to get stuck inside blood vessels, blocking blood flow, and are destroyed more quickly than their healthy counterparts. This can cause anemia, or a shortage of red blood cells, among patients.
Blood transfusions for SCD can cause iron overload in patients
To treat anemia, people with SCD commonly receive blood transfusions, which provide a supply of healthy blood cells. However, frequent transfusions may cause iron levels to become dangerously high, known as iron overload, which can cause organ damage.
DISC-3405 is an antibody-based therapy that aims to reduce iron levels by blocking the transmembrane serine protease 6 (TMPRSS6), a protein involved in iron metabolism. This is expected to increase the levels of hepcidin, a hormone that helps to control iron absorption and storage.
According to the company, the mechanism of action of the experimental therapy mimics what happens in people with mutations in the TMPRSS6 gene. Those mutations make these individuals less likely to experience iron overload.
A previous Phase 1 study (NCT06050915) tested the treatment’s safety and tolerability in 64 healthy adult volunteers. All were randomly assigned to receive single or multiple ascending doses of DISC-3405 or a placebo. Single doses ranged from 75 mg to 300 mg, while multiple ascending doses were given at 150 or 300 mg, once every four weeks.
The treatment was well tolerated at all single doses tested, with no serious adverse effects reported.
DISC-3405 also increased the blood levels of hepcidin in a dose-dependent manner, and led to meaningful and sustained reductions in iron levels, achieving a 50% to 80% reduction.
These effects were sustained for at least four weeks, supporting a potential monthly dosing regimen. Single and multiple DISC-3405 reduced hemoglobin levels and the proportion of red blood cells, and were able to block iron dietary absorption, supporting its use for treating iron overload.
Trial’s main goal is testing safety, effectiveness of DISC-3405
The main goal of the newly launched Phase 1 trial testing DISC-3405 in SCD is to assess the treatment’s safety and tolerability for up to 36 weeks, or about nine months. It will also assess DISC-3405’s pharmacodynamics — the therapy’s impact on the body and its mechanism of action — and its pharmacokinetics, or how the therapy moves inside the body.
The company is also advancing a Phase 2 trial (NCT06985147) that’s testing DISC-3405 to treat polycythemia vera, a rare blood cancer marked by iron overload. Initial data from this trial is also expected next year.
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