FDA Clears Way for Clinical Trial of HDP-101

Heidelberg Pharma has been cleared in the U.S. to begin a clinical trial testing its investigational therapy HDP-101 for the treatment of multiple myeloma.

The U.S. Food and Drug Administration (FDA) allowed the start of a Phase 1/2a trial following the submission of an investigational new drug (IND) application. The company expects to enroll the first patient and administer the first dose of HDP-101 by June.

“We have been working towards this goal for many months and are delighted that the FDA has allowed us to proceed with the Phase I/IIa trial with HDP-101,” Andreas Pahl, PhD, chief scientific officer of Heidelberg Pharma, said in a press release.

HDP-101 is a novel investigational therapy belonging to the class of antibody-drug conjugates. It is made up of an antibody that specifically binds to B-cell maturation antigen (BCMA) — a protein found at high levels in multiple myeloma cells — linked to a toxic compound.

When the antibody binds to its target, it releases the compound into cancer cells, destroying them without damaging healthy cells.

HDP-101 specifically contains a toxic compound called amanitin, a natural molecule found in poisonous mushrooms that prevents cells from making messenger RNA, the intermediate molecules between DNA and proteins, eventually leading to their death. Of note, amanitin does not require that cancer cells enter cell division to exert an effect, unlike most other compounds used in similar treatments, meaning it also could destroy dormant cells or cells involved in drug resistance.

Using anti-BCMA antibodies developed at the Max Delbrück Center for Molecular Medicine in the Helmholtz Association, in Germany, Heidelberg synthesized several antibody targeted amanitin conjugate (ATAC) molecules for myeloma and generated comprehensive preclinical data. Based on these data, the company selected HDP-101 as its lead candidate for clinical development.

In experiments performed in the laboratory, HDP-101 was safe, well-tolerated and showed a strong anti-tumor activity, leading to complete tumor remission in mouse models for multiple myeloma even at very low doses.

Following these positive preliminary results, Heidelberg began designing a first-in-human clinical trial, in collaboration with clinical centers in the U.S. and Germany.

“Developing a completely novel drug candidate to the point of first-in-human testing is a complex process. Therefore, the start of clinical development of the first candidate from our ATAC platform is an important milestone for us,” Pahl said.

The upcoming study will be conducted in two parts. In a dose-escalation phase, a total of 36 patients will receive ascending doses of HDP-101 to determine its maximum tolerated dose and the optimal dose for further tests.

Then, the dose-expansion Phase 2a part will enroll 30 additional patients to continue investigating the safety and effectiveness of the established dose.

Preclinical studies suggest that amanitin is particularly effective in a subset of patients carrying 17p deletion mutations, which usually is associated with high-risk and poor prognosis. Thus, patients in this phase will be divided based on their 17p deletion status to clarify the clinical relevance of this marker.

The company now is working to submit the study protocol to the Paul-Ehrlich-Institut in Germany.