Annamycin has little to no cardiotoxicity, avoids multidrug resistance, has been shown to be more potent in AML cell lines and has shown activity in patients for whom standard of care has failed.
Annamycin is an anthracycline we are developing for the treatment of relapsed or refractory acute myeloid leukemia or AML. Anthracyclines have been the cornerstone of AML treatment regimen for over 50 years. Together with another chemotherapeutic agent known as cytarabine, the combination is often referred to as “7+3 induction therapy” and its purpose is to induce remission sufficient to allow for a successful bone marrow transplant. Currently, the only viable long-term option for most acute myeloid leukemia patients is a bone marrow transplant, which is successful in a considerable number of patients. However, to qualify for a bone marrow transplant, patients must first succeed with induction therapy and, unfortunately, current induction therapies only work for around 20% of patients.
One of the leading anthracyclines used for induction therapy in acute leukemia patients is doxorubicin, which has reported over $700 million in annual revenues. Despite the importance and success of approved anthracyclines like doxorubicin, they are all unfortunately cardiotoxic, which can result in damage to the heart and limit the dosage amount that may be administered to patients. Additionally, the tumor cells being treated often have or develop resistance to the first line anthracycline, often through what is called “multidrug resistance” making them capable of purging themselves of the current anthracyclines and limiting the effectiveness of the therapy. Consequently, there remains no effective therapy for the vast majority of these patients and most will succumb quickly to their leukemia. This is where we believe Annamycin can be a complete game-changer.
Annamycin is a unique next-generation liposome formulated anthracycline (also referred to in literature as “L-Annamycin”) that has been designed to eliminate cardiotoxicity and avoid the multidrug resistance mechanisms that often defeat currently approved anthracyclines. In animal models designed to test for cardiotoxicity, Annamycin was shown to be non-cardiotoxic and in human clinical trials focused on leukemia, it showed fewer dose-limiting toxicities than are normally experienced with doxorubicin (one of the leading first-line anthracyclines used for induction therapy).
Annamycin has been tested in 6 prior clinical trials and 114 patients with little to no reported cardiotoxicity, including two clinical trials focused on leukemia, treating patients who had relapsed from or were refractory (nonresponsive) to first-line induction therapy. Each of these trials was conducted by a prior developer of Annamycin, and not by our company.
Annamycin demonstrated efficacy in 8 of 16 patients in a Phase I study in adult relapsed or refractory AML patients, with 6 of 14 patients completely clearing leukemic blasts. The reason only 14 (rather than 16) patients were tested for leukemic bone marrow blasts is that 2 of the 16 patients succumbed to their disease before bone marrow testing could be completed.
A 30-patient dose-ranging Phase I/II study in acute lymphocytic leukemia demonstrated a similar efficacy profile, with 3 of 8 patients treated with the maximum tolerable dose clearing their leukemic blasts to a level sufficient to qualify for a bone marrow transplant. One of these patients went on to receive a successful curative bone marrow transplant. The results of this most recent trial were reported in the journal Clinical Lymphoma, Myeloma & Leukemia in 2013 (Phase I/II Trial of Nanomolecular Liposomal Annamycin in Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia, Clinical Lymphoma, Myeloma & Leukemia, Vol. 13, No. 4, 430-4, 2013).
Acute Leukemia Patients
We believe Annamycin may give new hope to patients who have run out of options.
We believe Annamycin is better than the currently approved induction therapy drugs in four key ways:
- it has demonstrated clinical activity in a patient population for whom there are currently no effective therapies,
- it appears to be capable of avoiding the “multi-drug resistance” mechanisms that often limit the effectiveness of currently approved anthracyclines;
- it appears to be capable of avoiding the “multi-drug resistance” mechanisms that have been associated with limiting the effectiveness of currently approved anthracyclines;
- in certain AML cell lines, it has been shown to be more potent than one of the leading approved anthracyclines.
Clinical Development Strategy
If Annamycin can be shown to be an effective induction therapy for relapsed or refractory AML patients, we believe its lack of cardiotoxicity could make it an ideal first-line therapy for this disease. However, the regulatory pathway for first-line approvals is longer and more expensive than approval as a second-line therapy where there exists a significant unmet need. For this reason, we are intending to seek approval as a second-line therapy for AML patients who have not responded adequately to first-line therapies (estimated at around 80% of AML patients).
We believe the results generated by Annamycin’s prior developer would have been sufficient to warrant an accelerated approval pathway, had the trial been properly concluded. Unfortunately, the developer was unable to continue funding through completion and final report, so the data are not acceptable to regulatory authorities. Accordingly, our approach is to repeat Phase I/II trials that we believe will be sufficient to support an accelerated approval pathway, assuming similar results can be achieved.
We are currently studying Annamycin in two separate Phase I/II clinical trials, one in the US and one in Poland. We hope to provide important updates on the progress of these trials during 2019.