The U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority (BARDA) has awarded separate contracts totalling $56.3 million to four companies and one academic institution to support the development of five potential drugs for treating acute radiation syndrome.
The authority states that while such drugs will primarily be developed for the treatment of bone marrow, gastrointestinal, lung, and skin injury caused by radiation, they may also have utility in the treatment of thermal burns resulting from a nuclear detonation, and clinical applications in the treatment of side effects resulting from radio- and chemotherapies for cancer.
The award recipients are Neumedicines, RxBio, the University of Arkansas for Medical Sciences, Araim Pharmaceuticals, and Cellerant Therapeutics.
The $17 million 18-month contract awarded to Neumedicines will be used toward evaluating the safety and efficacy of the firm’s recombinant human interleukin-12 (rhuIL-12) candidate HemaMax™ and further developing manufacturing process for the drug. Under a 2008 BARDA contract, Neumedicines has already conducted proof-of-concept studies with HemaMax, which demonstrated that treatment reduces bone marrow damage caused by damaging radiation. The firm says additional financing over the next 3.5 years may also be available through milestone-based options to be exercised by BARDA, which could potentially bring the total value of the award to some $273 million.
In June the company began dosing healthy volunteers with HemaMax in a first-in-human Phase I study to evaluate the safety, tolerability, and pharmacokinetics of HemaMax for the treatment of hematopoietic syndrome of acute radiation syndrome (HSARS). The safety study will be followed by several larger safety studies in healthy human volunteers, prior to submission of a HemaMax BLA to the FDA, which is projected by 2016. HemaMax is also being developed for reducing the side effects of radiation or chemotherapy in cancer patients, and a Phase I clinical trial for the prevention of chemotherapy-induced thrombocytopenia (CIT) in patients with solid tumors is expected to begin in the first half of 2012.
RxBio has been awarded a two-year, $15 million contract to study the efficacy of RxBio’s lead compound Rx100, a small molecule analog of an endogenous, prosurvival molecule, and also to support process development for manufacturing. Earlier this month the firm reported data demonstrating that Rx100 protects against lethal, whole-body radiation when administered before, during, or up to 72 hours after exposure.
The two-year, $4.5 million contract awarded to the University of Arkansas for Medical Sciences (UAMS) support evaluation of the Novartis drug pasireotide (SOM230) for the treatment of radiation-induced gastrointestinal injury. UAMS’ development of the somatostatin analogue is being conducted under an agreement with Novartis, which originally targeted pasireotide for the treatment of Cushing disease. As part of the BARDA contract, the UAMS researchers will generate the data needed for Novartis to submit an NDA for approval of the drug for treating gastrointestinal injuries from radiation exposure. SOM230 appears to protect the intestine by reducing pancreatic secretions that exacerbate intestinal inflammation.
Araim Pharmaceuticals’ two-year, $3.1 million BARDA contract will fund studies with the clinical-stage candidate ARA 290, to evaluate whether the short peptide-based drug improves overall survival following administration 24 hours or more after exposure to high doses of ionizing radiation. ARA 290 is designed to mimic the three-dimensional structure of the tissue protective region of an endogenous protein that Araim says has several biological functions, one of which is to interact with a tissue-protective receptor, shutting down the local inflammatory reaction. ARA 290 is already in clinical development for reducing neuropathic pain in patients with critical limb ischemia, diabetes, or sarcoidosis, and for patients with rheumatoid arthritis. The drug’s cognitive effects are separately being evaluated in normal volunteers, with a view to further development as a treatment of depression.
Cellerant Therapeutics’ $16.7 million contract follows on from a 2010 BARDA award, and will support continued development of CLT-008, a myeloid progenitor cell-based therapy for the treatment of neutropenia caused by exposure to high levels of ionizing radiation. CLT-008 contains only early-to-late-stage myeloid progenitor cells, and not the mature T cells that can cause immune reactions, and so will not require immune system matching, the firm claims. Animal models have demonstrated the treatment can effectively prevent lethal bacterial and fungal infections after radiation exposure. The product is also being developed for use in patients with blood disorders, and those receiving bone marrow or cord blood transplants.