FDA Places HPN217, Immunotherapy for Advanced Disease, on Fast Track
The U.S. Food and Drug Administration (FDA) has given fast track designation to Harpoon Therapeutics’ HPN217 as a potential immunotherapy for people with relapsed, refractory multiple myeloma (RRMM) who have tried at least four prior therapies.
Fast track status is given to therapies that show potential in addressing serious conditions for which available treatments fall short. It is meant to speed their clinical development and regulatory review — enabling a rolling review and qualification for accelerated approval and priority review.
Rolling review means the company can submit sections of a regulatory application as they come ready, rather than waiting for every section to be completed before the application can be reviewed by the agency.
“We are pleased that HPN217 has received FDA Fast Track designation because it highlights the serious unmet medical need for patients with relapsed, refractory multiple myeloma who received multiple lines of therapy,” Julie Eastland, Harpoon’s president and CEO, said in a press release.
HPN217 is currently being tested in heavily treated RRMM patients in a Phase 1/2 clinical trial (NCT04184050). Enrollment is ongoing at sites across the U.S., France, Germany, and Spain; more information can be found here.
“We are focused on selecting an initial dose to study in the expansion phase of the ongoing Phase 1/2 clinical trial in the first half of this year as we progress HPN217 forward as an innovative new treatment option for these patients,” Eastland added.
Co-developed by AbbVie, HPN217 is a form of immunotherapy designed to direct cancer-killing immune T-cells specifically toward myeloma cells, promoting their death and leaving healthy cells largely unharmed.
Created with Harpoon’s Tri-specific T-cell Activating Construct (TriTAC) platform, the therapy intends to act as a bridge between T-cells and cancer cells by binding to the CD3 surface receptor on T-cells, and the B-cell maturation antigen (BCMA) found at high levels on the surface of myeloma cells. This link promotes an immune response against cancer cells.
While the mechanism is similar to that of a bispecific antibody, HPN217 is much smaller and more stable in the bloodstream, potentially allowing less frequent dosing and providing greater benefits.
The two-part Phase 1/2 trial is evaluating the therapy’s safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary effectiveness in up to 114 adults with RRMM who received at least three prior lines of treatment. These include a proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor.
Pharmacokinetics refers to the therapy’s movement into, through, and out of the body, while pharmacodynamics comprise its effects on the body.
In the study’s ongoing dose-escalation part, participants receive one of several increasing doses of HPN217 directly into the bloodstream once a week. Researchers will then determine the optimal dose to be evaluated in a larger group of patients in its expansion part.
The second part will only include patients who had not received any previous BCMA-targeting therapies.
Interim data from the study’s first part in 37 patients, treated at doses between 5 and 3,240 micrograms per week (µg/week), were presented at the 2021 American Society of Hematology Annual Meeting and Exposition.
These early results showed that the therapy was generally well-tolerated, with no serious or life-threatening cytokine release syndrome (CRS) being reported and one report of a dose-limiting toxicity, suggestive of liver damage, that was resolved. CRS is a serious immune reaction that can be triggered by certain types of cancer immunotherapies.
The maximum tolerated dose had not yet been reached.
Clinical responses were also observed in patients given higher doses.
In the group receiving HPN217 at 2,150 µg/week, seven out of eight (88%) patients showed reduced or stable disease. Disease reduction was detected in five of them (63%): a stringent complete response (no detectable cancer), a very good partial response, and three partial responses.
Another stringent complete response was observed in a patient given the 2,860 µg/week dose.
As per the agreement signed between Harpoon and AbbVie in 2019, Harpoon will be in charge of developing HPN217 through Phase 1/2 studies, after which AbbVie may choose to license the therapy and carry out all subsequent development, manufacturing, and commercialization.
HPN217 was previously designated an orphan drug by the FDA for this same patient group. This designation also aims to speed the therapy’s development by providing regulatory support and financial benefits, as well as a marketing exclusivity period of seven years should it be approved.