The FDA granted KRN5500 a second Orphan Drug Designation, this time for the treatment of multiple myeloma.
In our article below we summarize some publications highlighting data from KRN5500 in both neuropathy and multiple myeloma.
We believe DARA's commercial business is worth $15 to $20 million. KRN5500 adds another $10 to $15 million in value within our model.
Investors are getting DARA's commercial business at fair-value at today's price. We believe they are getting KRN5500 for free. If a deal can be struck, we see sizable upside.
On June 16, 2014, DARA BioSciences, Inc. (DARA) announced that the U.S. Food and Drug Administration (FDA) had granted Orphan Drug Designation (ODD) to KRN5500 for the treatment of multiple myeloma (MM). This is the second such award for the drug following the company's announcement in late February 2014 that the agency granted Orphan Drug Designation to KRN5500 for the parenteral treatment of painful, chronic, chemotherapy-induced peripheral neuropathy (CCIPN) that is refractory to conventional analgesics.
We believe this is very positive news for the company. The application was approved on first cycle review by the agency, with data supporting the application largely taken from early-stage trials and a comprehensive publication in 2012 which we discuss below. We see this second ODD as validation for the company's efforts to pursue further development of the compound. This clearly makes KRN5500 even more attractive to potential pharmaceutical partners looking to push forward with a phase 2b study in CCIPN or Phase 2a study in MM.
…Background on KRN5500…
KRN5500 an intravenous semisynthetic derivative of the nucleoside-like antineoplastic antibiotic spicamycin, originally isolated from the bacterium Streptomyces alanosinicus. The drug was originally developed by Japan's Kirin Brewery in an effort to identify new anti-cancer agents that induce apoptosis and differentiation of myeloid leukemia cells. The work was performed in collaboration with the Massachusetts General Hospital (MGH), the National Cancer Institute (NCI), and Eastern Cooperative Oncology Group (ECOG) in the U.S. Preclinical data demonstrated that KRN5500 has significant in vitro activity against human chronic lymphocytic leukemia (CLL) cells, thus providing support for advancement into clinical trials for patients with CLL, as well as those with acute myeloid leukemia (AML) and solid tumors. In July 2011, a paper published by H. Miki et al in the British Journal of Haematology outlines the potential anti-myeloma effects of the drug.
Four human clinical trials have been conducted in cancer patients, including one in Japan and three in the U.S. A total of 91 patients with solid tumors have been treated with intravenous fusions of KRN5500 with doses of up to 21 mg/m2 and weekly doses of up to 42 mg/m2. Unfortunately, no objective antitumor response was observed at the maximum tolerated dose (MTD) in any of these programs. A paper outlining the Phase 1 results with KRN5500 for the treatment of refractory solid tumors in 26 patients was published in Clinical Cancer Research in November 2003. Authors from MGH conclude, "There were no objective responses, although 3 of 17 evaluable patients exhibited disease stabilization for 5-6 cycles" (Supko et al., 2003).
Despite the lack of meaningful objective response in solid tumors, potent neuropathic pain reduction was observed in a significant number of patients. Analysis of these finds was published in the Journal of Pain and Symptom Management in April 2012. The authors conclude, "At study endpoint, KRN5500 exhibited a significant median decrease in pain intensity from baseline of 24% compared with 0% for placebo (P=0.03). The median for largest weekly reduction in target pain intensity was 29.5% for KRN5500 and 0% for placebo patients (P=0.02)" (Weinstein et al., 2012). We present some of the key additional data from that study below.
Based on these findings, KRN5500 was reformulated, specifically to remove excipients that caused severe gastrointestinal side-effects in the original cancer trials, and development was moved forward in CCIPN. CCIPN is a type of pain that results from nerve damage and is characterized by an abnormal hypersensitivity to innocuous, as well as noxious stimuli. This type of pain is extremely difficult to manage, fails to respond to standard analgesic interventions including opioids, and often worsens over time. There are currently no FDA approved treatments for CCIPN. Given the void in the market and peer-reviewed data supporting potential utility of the drug, the U.S. FDA granted Fast Track status for KRN5500 in CCIPN in August 2011. As noted above, in February 2014, the FDA granted Orphan Drug Designation to a sub-population of around 150,000 to 200,000 CCIPN patients in the U.S. each year. KRN5500 is ready to begin Phase 2b testing in CCIPN later this year.
…Impetus For MM…
According to management, a significant number of multiple myeloma patients experience painful neuropathy associated with their treatment options, including use of thalidomide or bortezomib. Data supports this population being in the range of 16,500 patients in the U.S., or around 75% of the total 22,000 myeloma patients diagnosed in the U.S. each year. Multiple myeloma is a plasma cell malignancy characterized by the presence of osteolytic bone destruction causing severe bone pain, pathological fractures, and hypercalcaemia (Kyle & Rajkumar, 2008). Peer-reviewed research supporting the potential utility of KRN5500 in MM comes from a July 2011 paper published in the British Journal of Haematology by researchers at the Department of Medicine and Bioregulatory Sciences at The University of Tokushima in Japan. The paper discusses several cell proliferation assays and in vivo animal studies comparing KRN5500 in various MM disease models. Below we present several of the primary conclusions from that study:
KRN5500 suppresses the growth of myeloma cells in a time- and dose-dependent manner by inducing G1 arrest and apoptosis: The authors analyzed the effects of KRN5500 on MM cell growth by examining seven MM cell lines and seven primary MM cells incubated with various concentrations of KRN5500 for 72 hours and measuring cell viability by WST-8 cell proliferation assay. The figure below shows the relative suppression of cell growth in MM cell lines in a time- and dose-dependent manner. The effect of KRN5500 on normal haematopoietic stem cells was also examined using colony assay and no apparent effect was found....
MFG
Chali
|
Thread abonnieren
