FDA grants Fast Track Review to Tri-Specific Antibody HPN217 to treat Relapsed/Refractory Myeloma

The clinical stage development company, Harpoon Therapeutics, has announced recently that their development product HPN217 (a tri-specific antibody) was granted ‘Fast Track’ designation by US FDA. HPN217 has been developed to treat myeloma patients whose disease has relapsed or become refractory following several prior lines of treatment.

“Fast Track is a process designed to facilitate the development, and expedite the review, of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier.”

One needs to understand, however, that Fast Track does not mean that final approval is imminent. The FDA MAY grant Fast Track based on the early results of human clinical studies (basically Phase I safety/efficacy/dose ranging trial(s)) that give an indication of clinical benefit to a target patient population. As such, FDA has given an early indication that HPN217 has clinical benefit. Fast track designation does not mean, however, that final approval will automatically be forthcoming in the future. That can only happen once the full set of all clinical data are reviewed.

HPN217, co-developed by AbbVie, targets the BCMA protein found on the surface of myeloma cells and is one of quite a few different products that are currently being evaluated in various clinical trials. What is different about HPN217? The product is a fairly small protein that binds to three different targets:

• CD3: a protein found on the surface of T-cells (cells to be used to kill cancerous cells),
• BCMA: a protein on the surface of the myeloma cells;
• Albumin: found in our blood. This last part is important in that it extends the half-life of the total construct [myeloma cell – HPN217 – T-cell]. Longer half-life is of value, and interest, to the patient in that it allows for a longer interval between successive doses.

The part of HPN217 that binds to albumin is located between the two parts that bind to CD3 and BCMA. A nice graphical presentation of the total construct can be seen in this link (from a presentation at the most recent ASH forum).

The Phase I study included 37 patients, and some relevant data are provided below:

Patient Characteristics

• Median age : 71 years
• Median duration of disease : 8 years
• Median number of prior therapies: 7
• The overwhelming majority (+ 90 %) of the patients had been treated before with an immunomodulator (mostly Revlimid and/or Pomalyst), a proteasome inhibitor (mostly Velcade and/or Kyprolis) and/or an anti-CD-38 antibody (mainly Darzalex).  Twenty seven percent (27%) of the patients in the clinical trial had also been previously treated with one of the anti-BCMA products (either already FDA approved or in a clinical setting).

Dosing

Weekly infusions of 1 hour are given. The company is still fine-tuning dosing schedules and dosing loads, exploring both step-dosing as well as less frequent dosing.

Side Effects

Adverse reactions included mainly anemia, fatigue, and cytokine release syndrome, all at manageable/tolerable levels.

Impact

HPN217 has shown clinical activity at various dose levels. The highest number of patients (8 out of 37) were dosed at 2,150 micrograms per infusion. At that level the overall response rate was 63% with an 88% Disease Control Rate (this means that the patients in question had stable disease or better). 13% achieved stringent complete response, 13% reached very good partial response, 38% very good partial response including with one patient who had relapsed after prior anti-BCMA targeting therapy.

We need to remind ourselves, though, that these are results from the Phase I study with a limited cohort  of patients. Harpoon Therapeutics is still several years away from completing the necessary Phase II/III human trials and going through the full FDA review process. It will be a worthwhile effort for us, patients, to follow future results to be published during that period of time. Fingers crossed; we will end up with one more product in the future toolkit to treat our disease.