Actinium Pharmaceuticals (NYSE MKT:ATNM) expects to begin a Phase 3 trial in the second half this year of its Iomab-B drug candidate as a conditioning agent in elderly patients with relapsed/refractory acute myeloid leukemia (AML) prior to a bone marrow transplant (BMT).
The company also has a second drug candidate, Actimab-A, now in a Phase 1/2 study in elderly, untreated AML patients.
“We believe, as potential breakthrough therapies, Iomab-B and Actimab-A may achieve successful market penetration, given strong support from key opinion leaders and significant unmet medical need,” president and CEO, Kaushik Dave, says in an interview with BioTuesdays.com.
Dr. Dave explains that Actinium develops cancer drugs with its Alpha Particle Immunotherapy (APIT) platform. The technology is based on attaching powerful alpha emitting radioisotopes, such as Actinium 225 or Bismuth 213, to monoclonal antibodies, which are large molecules capable of binding specifically to cancer cells, where the alpha emitter effectively targets and selectively kills the cancer cell.
Actinium licensed Iomab-B from the Fred Hutchinson Cancer Research Center, while Actimab-A was co-developed with the Memorial Sloan Kettering Cancer Center. A large safety database and proof-of-concept data have been obtained from more than 300 patients in five Phase 1 and Phase 2 trials with the two drug candidates.
Dr. Dave notes that there are also seven physician trials ongoing with the antibody in Iomab-B for other indications, which could be used to expand the initial indication beyond AML. “Iomab-B represents a potentially faster pathway to a BMT, with fewer side effects,” he adds.
The current approach to BMT conditioning for relapsed/refractory elderly AML patients is chemotherapy for patients who can tolerate it.
Dr. Dave points out that the time from chemotherapy to a BMT in the elderly who qualify for BMT is currently 28-to-42 days, while Iomab-B gets all patients ready for BMT in about 10 days, getting them there more safely and without the need for chemotherapy.
“This is important because AML is a galloping disease,” he explains. “Leukemic blood cancer cells in AML double in number every three days, and patients go downhill very quickly.”
Most relapsed and refractory AML patients over the age of 55 are either unable to endure another dose of chemotherapy or are in situations where chemotherapy has no effect on their disease and they move into hospice, or end-of-life, care. Iomab-B has the potential to prepare all of these patients for a BMT. “We have the potential to provide a treatment alternative to patients with no options,” Dr. Dave adds.
Actinium is advancing Iomab-B to a Phase 3 study on the strength of Phase 1/2 data, which demonstrated a complete response rate of 100% and a one-year survival rate of 30% and a two-year survival rate of 19%. That compares with retrospective data of one-year survival of 10%, with chemotherapy and BMT, and a zero survival rate after two years in older relapsed and refractory patients.
According to Dr. Dave, if a BMT patient is still alive after two years, the patient effectively has been cured. He adds, “…and we have cured one-in-five.”
Based on an end-of-Phase 2 meeting with the FDA, Actinium’s Phase 3 trial will enroll 150 AML patients aged 55 and older, with 75 patients in a treatment arm where they will be treated with Iomab-B and 75 in the control arm receiving conventional chemotherapy care followed by bone marrow transplant where feasible. The primary endpoint is six months of durable complete response, with a secondary endpoint of overall survival at one year.
Dr. Dave figures enrollment will take about 12 months, with an additional nine months or so to obtain primary data.
The top 10 BMT centers in the U.S. currently perform 30% of AML transplants, and eight of these centers have already indicated that they will participate in the pivotal trial.
Actinium is targeting FDA approval of Iomab-B for AML in 2017 and a launch in 2018. The company estimates the worldwide potential of the drug at $750-million for AML alone.
The Fred Hutchinson Cancer Research Center is currently conducting Phase 1 and 2 trials with Iomab-B in patients with myelodysplastic syndrome, acute lymphoblastic leukemia, non-Hodgkin’s lymphoma and Hodgkin’s disease. The company figures these blood cancers could boost Iomab-B’s total market potential to more than $4-billion.
Actinium’s second platform is using the HuM 195-alpha antibody linked with an alpha-emitting radioisotope to attack AML.
Using a first generation drug candidate, Bismab-A, the company obtained positive proof-of-concept data, demonstrating that Bismab-A resulted in a median survival in elderly AML patients that was four times greater than shown by historical data.
According to Dr. Dave, a short half-life and high cost of goods prompted the company to replace Bismab-A with a second-generation product, Actimab-A, which is 500 times more potent than Bismab-A, enabling the use of a smaller dose. Actimab-A also has a much longer half than Bismab-A and significantly reduced cost of goods.
Actimab-A is currently in a Phase 1/2 dose escalation study, with final data expected in mid-2015 from the Phase 1 portion of the study. “No toxicity has been observed to data outside of blood cells at doses expected to be clinically effective,” he points out.
At the end of 2014, the company released interim Phase 1 data from the study. Most notably, median overall survival of the seven secondary AML patients in the study was 9.1 months, compared with historical norms of two-to-five months, depending on the treatment modality. In addition, two patients lived longer than one year, and one patient surprisingly survived for 24 months.
“Based on the favorable safety profile in clinical trials to date, Actimab-A has the potential to be a low intensity therapy for older AML patients to extend overall survival and quality of life, especially since intensive chemotherapy is associated with a high mortality rate and limited benefits to high-risk patients,” Dr. Dave contends.
He says Actinium’s APIT technology and drug candidates are covered by 39 issued and pending patents. “Our proprietary strategy for Iomab-B involves trade secrets, orphan drug exclusivity and data exclusivities with intent to file process, labeling and other patents, raising the barrier to entry by anyone else,” he adds.
Shares of Actinium closed at $2.87 on Friday. In an initiation report last July, Canaccord Genuity analyst, John Newman, set a $16 price target for Actinium but noted that there was potential upside to about $33, if FDA approves both assets.