|Q&A: Actinium Pharmaceuticals Inc. CEO Eyes Orphan Drug Application for Flagship Drug|
|Wednesday, 07 January 2015 00:00|
Actinium Pharmaceuticals Inc. a biopharmaceutical company developing innovative targeted payload immunotherapeutics for the treatment of advanced cancers announced last month that the US Food and Drug Administration (FDA) had granted orphan-drug designation for Actimab-A, an alpha radiolabeled antibody being developed for newly diagnosed AML in patients over the age of 60.
Actimab-A is currently in a multicenter Phase 1/2 trial clinical trial. The company also recently reported interim results for the Actimab-A trial that was published in the American Society of Hematology’s journal, Blood. We sat down with Kaushik J. Dave, President and CEO of Actinium to discuss these new significant events for Actinium.
GARZA: Can you give us some background on of the breakthrough or novel approach Actinium is pursuing in the oncology space?
DAVE: Our approach called “Targeted Payload Cancer Therapeutics” (TPCT) combines the ability of a target agent (monoclonal antibody- mAb) to bind to a cancer cell and the ability targeted radiation to kill cancer cells. Essentially the antibody acts as the GPS guided missile to get directly to the cancer cells and avoid healthy cells and the attached radioactive isotope is the killing weapon to eradicate the cancer.
GARZA: Can you describe some of the programs at Actinium?
DAVE: Our lead program, Iomab-B, is set to enter late stage trials at Fred Hutchinson Cancer Center (FHCC) and Memorial Sloan Kettering Cancer Center (MSKCC), among other leading cancer centers in the US most recently Baylor Sammons Cancer Center.
For Iomab- B we are currently preparing a single, pivotal, multicenter Phase III clinical study in refractory and relapsed Acute Myeloid Leukemia (AML) patients over the age of 55. Our second program Actimab-A, which we believe could significantly change the treatment landscape in AML on other cancers, is in a Phase I/IItrial for newly diagnosed AML patients over the age of 60 in a single-arm multicenter trial.
Iomab-B has already been successfully used as a myeloconditioning/myeloablative agent in over 250 patients with incurable blood cancers. In both Phase I and Phase II trials Iomab-B has delivered strong 1 and 2-year survival data which at 2-years is essentially considered curative for a patient group with limited to no options other than supportive care and weeks or month to live. The only potentially curative treatment option for those patients is bone marrow transplantation (BMT) but vast majority of patients over the age of 55 are either ineligible for myeloablative conditioning ( high dose chemotherapy) due to concomitant conditions or have a high burden and/or very resistant disease that makes reduced dose conditioning futile. Iomab-B can potentially change this equation enabling a majority of patients the opportunity to have a BMT and possibly be cured.
GARZA: You recently received a nod from the FDA for Orphan Drug Status. What drug was it for?
DAVE: That would be for Actimab-A, our second program which uses an alpha emitter Actinium 225, hence the name of the company. Alpha-emitting particles are highly targeted and have potency 100-fold higher than beta’s which increase the killing power against targeted tumor cells and given their extremely short range, which further limits the damage inflicted on healthy tissues. Actimab-A is a second generation product, which to date has shown a good safety profile and superior potency compared with our first generation compound. The development of the first generation compound, which had positive Phase II data, was discontinued due to the high cost of manufacture and short half-life which made it not commercially viable. Actimab-A addresses both of these issues and provides greater potential based on its initial safety data and stronger potency when compared at the same stage of development.
GARZA: Where are some of the key milestones in the coming months?
DAVE: In a Phase II study, Iomab-B was shown to accelerate the ability to move a patient to bone marrow transplant by about one month, and significantly improve survival in a patient population with few to no options. Phase 2 results showed survival at year 1 of ~ 30% and survival at year 2 of ~20%. This compares very favorably with survival for chemotherapy and conventional bone marrow transplant of 10% in year 1 and essentially 0% or no survival at 2 years post treatment in this targeted patient population.
Based on this compelling data, we had a very favorable end of Phase II meeting with the FDA and are now preparing to move to a Phase 3 trial in mid-2015. If the trial goes as planned and we receive FDA approval, we would anticipate commercialization in 2017.
The second program, Actimab-A, is continuing its clinical development in a Phase I/II trial for newly diagnosed AML patients over the age of 60 in a single-arm multicenter trial. We recently reported positive interim data from the ongoing Phase I/II trial of Actimab-A in older patients with newly diagnosed AML demonstrated median overall survival ("OS") of the seven secondary AML patients (with prior myelodysplastic syndrome, or MDS) in the study was 9.1 months, which is a prolongation of life compared to historical norms of typically 2 to 5 months. Older AML patients are already higher risk, with secondary AML patients considered to have the more severe and less treatable form of AML, and the shortest expected survival.
In this interim analysis, a total of 9 patients were evaluated thus far with a median age of 76 (range 73-81). All had intermediate or poor risk cytogenetics, and 7 of 9 patients had secondary AML as a result of prior MDS. These 7 secondary AML patients had a median OS of 9.1 months from study entry (range 2.3-24 months). Of these, 2 patients lived longer than 12 months and the longest surviving patient lived greater than 24 months. Overall, for all 9 patients median overall survival was 5.4 months.
GARZA: How big is the market for each and what are the other indications/markets you are or may pursue?
DAVE: There are approximately 18,900 AML patients diagnosed each year of which ~2/3 are over the age of 55, a majority of which will be relapsed or refractory.. We think the WW market opportunity for Iomab-B in this initial indication is about $700- $800 million WW with potentially more than $4 billion WW when you include some of the other potential indications that are also in clinical development. For Actimab –A, in newly diagnosed patients over the age of 60, or roughly 60% of AML patients, we estimate the market opportunity in this indication alone is in excess of $900 million worldwide.
GARZA: Who does this put you in competition with?
DAVE: For the relapsed and refractory market for patients +55, there have been no drugs approved or currently on the market for AML in decades. There a few companies pursing AML using different approaches, but we are confident based on our preliminary data and input from our world-class scientific advisory board, we believe Iomab-B will address an underserved patient population with limited to no options with a potentially curative treatment regimen.
With respect to Actimab, we believe it should provide an alternative to or complimentary treatment with current or in development therapies based on its current safety profile and potency exhibited in clinical trials to date. Let me give you some perspective on the value the market is placing on targeting radio therapeutics. The most recent success in this space is Algeta who received approval last year for Xofigo a radiotherapy for prostate cancer that has spread to the bone and was sold to Bayer for $2.9 billion earlier this year. We believe we have a more robust technology platform with the potential to address a number of cancer indications which we are studying. This supports our belief that there will be strong interest from potential partners as we continue to move the programs forward.
GARZA: Are you working with partners or what is your commercialization strategy?
DAVE: In the US, the BMT market is highly concentrated with approximately 30% of the market for allogenic BMT’s being performed in 10 leading cancer centers in the US, many of which will be participating in our clinical trials. We believe that with a small sales force, we can effectively address the market and commercialize Iomab-B on our own in the US. As we move forward, we will determine the best course for the development and commercialization outside the U.S.
With respect to Acitmab-A, given it used alpha emitters, it can be used in an outpatient setting and therefore be administered by a broader physician group. We would anticipate leveraging the Iomab-B salesforce to commercialize in the US to the top cancer centers, and partner for other physicians and healthcare settings.
For more information about Actinium Pharmaceuticals, log on to www.actiniumpharma.com