Welcome to your Update from the Clinic for the month of July. The cancer stem cell companies were back in the news last month. OncoMed initiated its ALPINE clinical trial of Tarextumab for pancreatic cancer, while Stemline Therapeutics announced an investigational new drug (IND) for SL-401 and initiation of clinical trials in two blood cancer indications. Fate Therapeutics also announced clearance of an IND to use its PROHEMA technology in inherited metabolic disorders. Read on to find out more.
The cancer stem cell company OncoMed (OMED) initiated its Phase 2 ALPINE (antibody therapy in first-line pancreatic cancer investigating anti-notch efficacy and safety) study investigating Tarextumab (anti-notch 2/3) for pancreatic cancer. The stem cell targeting antibody is being deployed for patients with previously untreated stage IV pancreatic cancer, an indication in dire need of new therapeutics.
The 5-year survival rate of this patient subclass is a mere 1 per cent. Tarextumab will be assessed as a combination therapy along with the chemotherapeutics Nab-Paclitaxel and Gemcitabine. The study is a clinical milestone for OMED, which is advancing a number of other stem cell-specific antibody candidates through early-stage safety studies. An additional four Phase 2 trials are anticipated in the coming nine months.
OMED’s industry peer, Stemline Therapeutics (STML), announced the opening of the corporate SL-401 IND, an antibody directed to the interleukin-3 receptor. STML will pursue blood cancers in the clinic, including a very rare cancer, blastic plasmacytoid dendritic cell neoplasm (BPDCN), and acute myeloid leukemia, the latter of which has a high relapse rate following first-line therapy due to the existence of cancer stem cells that sustain malignant growth.
The therapy has already been investigated in a physician-sponsored Phase I/II study, where seven of nine BPDCN patients showed a response, including five complete responses (disappearance of all signs of cancer). The SL-401 clinical program will be broad, and will address several myeloproliferative disorders that share a common IL-3+ progenitor cell, including mastocytosis, hypereosinophilic syndrome, myelofibrosis, and chronic myelomonocytic leukemia. STML will seek accelerated approval for all indications.
California-based Fate Therapeutics (FATE), which recently secured $20 million in debt financing, also announced an IND for its PROHEMA technology in patients with inherited metabolic disorders (IMDs) undergoing hematopoietic stem cell transplant. The company will begin enrolment for its PROVIDE (PROHEMA evaluation for the treatment of inherited metabolic disorders) study in pediatric patients with IMDs later this year. Clinical studies have already been completed investigating the therapy in patients with various blood cancers.
MiMedx (MDXG), a company specializing in the development of bioimplants created from amniotic membrane, announced filing of an IND with the FDA for the use of its allogeneic grafts for a group of indications. MDXG will subsequently file biologics license applications for its products should its clinical development programs be successful. The company’s two primary products, AmnioFix® and EpiFix®, are derived from placentas donated by women who elect to provide their placentas following full-term caesarean sections. Tissue is then processed using a proprietary process known as PURION®.
A peer-reviewed retrospective study of three commonly used cell-based wound healing technologies, including MDXG’s EpiFix®, and also Apligraf® and Dermagraft® (both owned by Organogenesis), showed that EpiFix® was most effective at treating diabetic foot ulcers (DFUs). Over the course of 12-weeks, 92 per cent of patients receiving the EpiFix® patch exhibited complete wound closure, versus 56 per cent and 30 per cent for Apligraf® and Dermagraft®, respectively. The rate of ulcer recurrence was also quite low, around 5.6 per cent, showing that the graft supported maintenance of healthy skin function following treatment. Prospective comparative effectiveness trials will be needed to substantiate the results.
Interestingly, as opposed to Apligraf® and Dermagraft®, which are both viable cell products derived from neonatal foreskin, EpiFix® is a non-viable cell-based product that is dehydrated prior to use. The graft preserves extracellular matrix, and a host of growth factors and cytokines, which drive wound healing and closure following its application. From a logistics perspective, this is highly favourable. It also appears to be beneficial from a cost perspective; EpiFix® starts at a cost of ~$330, depending on the size of the graft, which ranges from 14mm to 60mm. Apligraf and Dermagraft cost north of US$1,600 per graft, which is typically cut to size by the physician with waste being discarded.
Companies brave enough to go after wound healing have typically targeted DFUs due to the significant market size; however, it continues to be a space that remains challenging commercially due to the poor reimbursement climate offered by the CMS reimbursement schedule, which currently lumps cellular and acellular products together. More impactful clinical results, like those published by MiMedx, will help illustrate the value of cell-based wound healing products and improve their prospects for adoption.
Disclaimer: “Update from the Clinic” is a blog post generated by news flow from public regenerative medicine (RM) companies around the globe. As CCRM has public RM companies in its industry consortium, and the number of such companies is relatively limited on a global scale, Mark Curtis will sometimes include CCRM consortium members in his review. This blog post is provided for general information only and nothing contained in the material constitutes a recommendation for the purchase or sale of any security. The author is not a shareholder of any public RM company. To see a list of CCRM’s industry consortium members, please visit http://ccrm.ca/industry-consortium