US FDA may fast-track the approval process of Ariad Pharmaceutical’s investigational therapy AP24534 to treat chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
AP24534 has been granted orphan drug designation by both the U. S. Food and Drug Administration (FDA).
AP24534 is an investigational pan-BCR-ABL inhibitor. The molecule has broad potential applications in cancer.
Ariad is currently completing a Phase 1 clinical trial of oral AP24534 in patients with advanced hematological cancers and plans to begin a pivotal registration trial of AP24534 later this year.
Preclinical studies data as well as data from the Phase 1 trial show that AP24534 has hematologic, cytogenetic and molecular anti-cancer activity of AP24534 in heavily pretreated patients with resistant and refractory chronic myeloid leukemia (CML), including those with the T315I mutation.
In preclinical studies, AP24534 has also demonstrated potent inhibition of kinase targets associated with acute myeloid leukemia, as well as proliferation and angiogenesis in multiple solid tumors.
Orphan drug designation for AP24534 means that there is a lack of therapeutic options available for patients with CML or Ph+ ALL, who are resistant or refractory to currently available therapies.
Orphan Drug Designation also provides for special benefits, including research support, eligibility for protocol assistance and possible exemptions or reductions in certain regulatory fees during development or at the time of application for marketing approval.
Ariad expects to advance AP24534 into a pivotal registration trial later this year. The company also plans to pursue subsequent regulatory submissions for marketing authorization in these hematological cancers.
Chronic myeloid leukemia is characterized by an excessive and unregulated production of white blood cells by the bone marrow due to a genetic abnormality that produces the BCR-ABL protein.
Chronic myeloid leukemia starts with a chronic phase of production of too many white blood cells.
Then the disease typically evolves to more aggressive phases such as accelerated or blast crisis.
Ph+ ALL is a subtype of acute lymphoblastic leukemia that also carries the Ph+ chromosome that produces BCR-ABL.
Acute lymphoblastic leukemia has a more aggressive course than CML and is often treated with a combination of chemotherapy and tyrosine kinase inhibitors.
Since both of these diseases express the BCR-ABL protein, this would render them potentially susceptible to treatment with AP24534, Ariad said in a press release.
AP24534 has also received orphan designation is for CML and acute lymphoblastic leukemia in EU by the European Medicines Agency (EMA).
Ariad’s lead product candidate, ridaforolimus, is an investigational mTOR inhibitor in Phase 3 clinical development in patients with advanced sarcomas and is being developed in collaboration with Merck & Co., Inc.
AP24534 is Ariad’s second lead product candidate, an investigational pan-BCR-ABL inhibitor completing Phase 1 clinical development in patients with hematological cancers, notably chronic myeloid leukemia.
Ariad has an exclusive license to pioneering technology and patents related to certain NF-kB cell-signaling activity.