Positive Results Announced: APVO436 for AML, MDS

In a recent company update, via AccessWire, biotechnology company Aptevo Therapeutics Inc. (“Aptevo”) shared positive results from a Phase 1 dose-escalation trial. During the trial, Aptevo evaluated APVO436 for patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The therapy was developed using Aptevo’s proprietary ADAPTIR and ADAPTIR FLEX technologies.


According to Aptevo, APVO436 is:

an optimized ADAPTIR bispecific antibody candidate designed to redirect T-cell cytotoxicity through the dual targeting of CD3, a T-cell co-receptor that promotes cytotoxicity, and CD123, a cell surface receptor highly expressed in several hematological malignancies, including acute myeloid leukemia, acute lymphoblastic leukemia, hairy cell leukemia, myelodysplastic syndrome, and blastic plasmacytoid dendritic cell neoplasm. In preclinical studies, APVO436 was shown to redirect T-cell cytotoxicity against CD123-expressing tumor cells in both in vitro and in vivo assays.

By targeting both CD3 and CD123, APVO436 spurs the immune system to destroy cancerous cells. As described above, the therapy has also shown promise in preclinical studies. For example, in mice models of AML, those treated with APVO436 showed significantly longer survival rates than untreated animals. APVO436 is also designed to stay in the blood long enough to target and destroy cancerous cells.

Thus far, APVO436 received Orphan Drug designation from the FDA.

Phase 1 Data

During the Phase 1 dose-escalation trial, researchers explored the efficaciousness of different APVO436 doses. Altogether, 46 patients enrolled. Patients had either AML or MDS. Once enrolled, patients received escalating APVO436 infusions, administered intravenously. Doses ranged from 0.3 micrograms up to 60 micrograms. Study findings included:

  • Ultimately, the primary endpoint was determining an active dose for future studies. The trial did achieve this goal using doses found in Cohort 6.
  • In Cohort 6, there were 7 evaluable patients with relapsed AML. During treatment, 4 patients (57%) showed cancer stabilization. Of these patients, one had cancer progression after one month. However, the other three patients lived for between 246 and 281 days.
  • Following treatment, 2 patients achieved partial or complete remission.
  • Overall, APVO436 was relatively safe and well-tolerated. Neurological toxicity, found in other similar treatments, was not common in patients within this study.
  • Unlike other treatments which target CD123, APVO436 did not cause severe neutropenia (low neutrophil / white blood cell count).

More targeted and personalized treatments are needed for those with AML and MDS. APVO436 offers the opportunity to fulfill this need.

Myelodysplastic Syndromes (MDS)

Myelodysplastic syndromes (MDS) consist of a group of progressive conditions which prevent the bone marrow from producing enough healthy platelets, red blood cells, and white blood cells. In these bone marrow failure disorders, cells never grow and mature. Instead, they either remain in the bone marrow as immature cells or have very short lives. Altogether, there are five subtypes of MDS: refractory anemia, refractor anemia with excess blasts, refractory anemia with sideroblasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. However, doctors are not quite sure what causes MDS. Generally, MDS affects those older than 60. It also impacts males more than females. In around 50% of all diagnoses, MDS progresses and becomes AML. For low-risk patients, the approximate survival rate is 6 years. Alternately, this is only 5-6 months for high-risk patients.

Symptoms include:

  • Anemia (low red blood cell count)
  • Neutropenia (low white blood cell count)
  • Thrombocytopenia (low platelet count)
  • General malaise
  • Fatigue and/or lethargy
  • Petechiae
  • Heart palpitations
  • Frequent infections
  • Pallor (pale skin)
  • Easy bruising and bleeding
  • Chest pain
  • Shortness of breath

Acute Myeloid Leukemia (AML)

Leukemias are cancers which form in blood cells – or at least cells that would develop into blood cells. In the case of acute myeloid, or acute myelogenous, leukemia (AML), the cancer forms within the bone marrow. Normally, this spongy tissue inside bones contains stem cells which later develop into platelets, white blood cells, and red blood cells. But in patients with AML, the bone marrow instead produces abnormal blood cells, including abnormal myeloblasts (a white blood cell). As these abnormal cells crowd out healthy cells, the blood is unable to do its work. Risk factors for developing AML include age (65+), previous radiation exposure or cancer treatment, being male, and cigarette smoking. Symptoms include:

  • Pallor (pale skin)
  • Easy bruising
  • Unusual bleeding (frequent nose bleeds, periodontal bleeding)
  • Unintended weight loss
  • Fatigue and/or lethargy
  • Petechiae under the skin
  • Appetite loss
  • Shortness of breath
  • Night sweats
  • Fever with no known cause
  • Bone pain
  • Frequent infections
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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