Ronald Hoffman, MD, a professor of medicine, hematology, and medical oncology at Mount Sinai, discusses the design of an ongoing phase 2 trial (NCT04057040) evaluating the first-in-class synthetic hepcidin mimetic PTG-300 in patients with polycythemia vera. 

According to Hoffman, there are 3 components to the trial. The dose-finding component will determine the optimal dose of PTG-300 that can maintain a patient’s hematocrit levels below 45%, says Hoffman. 

Once the optimal dose has been established, patients will be randomized to continue on treatment with PTG-300 or placebo, Hoffman explains. The goal of this portion of the study is to determine whether erythrocytosis will return in patients who are receiving placebo. 

Finally, patients randomized to placebo will receive PTG-300 in the continuation phase of the study, Hoffman says. As the frequency of phlebotomy is a metric that is being used to determine the efficacy of PTG-300, eligible patients have to have had more than 3 phlebotomies over a period of 6 months prior to study entry, concludes Hoffman. 

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Ronald Hoffman, MD, discusses the design of an ongoing phase 2 trial evaluating the first-in-class synthetic hepcidin mimetic PTG-300 in patients with polycythemia vera. 


Dr. Hoffman on the Design of an Ongoing Trial Testing PTG-300 in Polycythemia Vera 

Ronald Hoffman, MD, a professor of medicine, hematology, and medical oncology at Mount Sinai, discusses the safety profile of the first-in-class synthetic hepcidin mimetic agent PTG-300 in patients with polycythemia vera (PV).

PTG-300 is under examination in an ongoing phase 2 study (NCT04057040), says Hoffman. The primary objective of this research is to introduce a novel therapeutic agent to the limited PV treatment paradigm. To date, a limited number of patients have received the agent, says Hoffman. A total of 8 patients were included on the trial; of those, 7 have received the treatment and 6 were considered to be evaluable. Notably, these patients were heavily dependent on phlebotomy, Hoffman notes.

Results from the trial showed that PTG-300 was tolerable with no notable adverse effects (AEs) beyond those associated with the administration of a subcutaneous drug, such as local irritation, says Hoffman. That effect was reported in several patients, but was found to be easily managed. Additionally, no allergic reactions to the drug were observed, nor did patients experience progression to myelofibrosis, myeloid leukemia, or myeloproliferative neoplasm (MPN) blast phase. Patients also did not experience a hemorrhagic or thrombotic event during the administration phase of the trial, Hoffman concludes.

Ronald Hoffman, MD, discusses the safety profile of the first-in-class synthetic hepcidin mimetic agent PTG-300 in patients with polycythemia vera.

Dr. Hoffman on the Safety Profile of PTG-300 in Polycythemia Vera

Ronald Hoffman, MD, professor of medicine, hematology, and medical oncology and director of the Myeloproliferative Diseases Program at The Icahn School of Medicine at Mount Sinai, discusses the advantages of self-administration with the investigational hepcidin mimetic PTG-300 for patients with polycythemia vera (PV).

PTG-300 is being evaluated in an ongoing phase 2 clinical trial (NCT04057040). Preliminary data have shown encouraging clinical activity and a tolerable safety profile in patients with PV.

The first-in-class agent is to be self-administered by patients subcutaneously, says Hoffman. Conventional treatment of patients with PV consists of repeated phlebotomies to maintain a hematocrit level below 45%.

Phlebotomies can cause elderly patients to become syncopal or exacerbate congestive heart failure, explains Hoffman. Additionally, the treatment can be frightening or traumatic for some patients.

Between phlebotomies, patients’ hematocrit levels are likely elevated, Hoffman adds. However, this often goes undetected as continuous testing is not currently implemented.

As such, the self-administration of PTG-300 may provide sustained hematocrit control, reduction of long-term thrombotic events, and systemic symptom relief. Additionally, patients may have improved satisfaction with the agent as self-administering medication will provide them more independence, concludes Hoffman.

Ronald Hoffman, MD, discusses the advantages of self-administration with the investigational hepcidin mimetic PTG-300 for patients with polycythemia vera (PV).



Dr. Hoffman on Advantages of Self-Administration With PTG-300 in Polycythemia Vera

Ronald Hoffman, MD, professor of medicine, hematology, and medical oncology and director of the Myeloproliferative Diseases Program at The Icahn School of Medicine at Mount Sinai, discusses the mechanism of action of the investigational hepcidin mimetic PTG-300 in polycythemia vera (PV).

Hepcidin regulates the absorption of iron into the body from the intestine, as well as the release of iron from macrophages, says Hoffman.

Patients with PV typically present with iron deficiency, which is exacerbated with phlebotomy, explains Hoffman. As such, hepcidin mimetics including PTG-300 could be a potential treatment for these patients.

PTG-300 administered subcutaneously may block the release of iron from macrophages, which could then serve as nursing cells that reduce the uncontrolled production of red blood cells, concludes Hoffman.

Ronald Hoffman, MD, discusses the mechanism of action of the investigational hepcidin mimetic PTG-300 in polycythemia vera.



Dr. Hoffman on the Mechanism of Action of PTG-300 in Polycythemia Vera

Ronald Hoffman, MD, professor of medicine, hematology, and medical oncology and director of the Myeloproliferative Diseases Program at The Icahn School of Medicine at Mount Sinai, discusses the current polycythemia vera treatment paradigm.

Patients under the age of 60 or who have not experienced a prior thrombotic event are typically treated with phlebotomy with the goal of maintaining hematocrit at a level of less than 45%, Hoffman explains.

Conversely, patients over the age of 60 or who have had a prior thrombotic event usually receive myelosuppressive therapy, such as pegylated interferon or hydroxyurea, which is the current standard of care. If patients progress on those agents, they will be given the JAK1/2 inhibitor ruxolitinib (Jakafi). Additionally, it is not uncommon for patients to receive aspirin, Hoffman adds.

All these therapeutic strategies are geared toward reducing the incidence of thrombosis. However, the most important metric is sustaining hematocrit at a level of less than 45%, Hoffman says. Notably, none of the available treatment options prevent disease progression to myelofibrosis or acute myeloid leukemia (AML), Hoffman concludes.

Ronald Hoffman, MD, discusses the current polycythemia vera treatment paradigm.

Ronald Hoffman, MD

Articles

Dr. Hoffman on the Design of an Ongoing Trial Testing PTG-300 in Polycythemia Vera

Dr. Hoffman on the Safety Profile of PTG-300 in Polycythemia Vera

Dr. Hoffman on Advantages of Self-Administration With PTG-300 in Polycythemia Vera

Dr. Hoffman on the Mechanism of Action of PTG-300 in Polycythemia Vera

Dr. Hoffman on the Current Polycythemia Vera Treatment Paradigm