Industry Update: Clinical trials
Latest developments compiled from 01 February — 31 March 2015.
Latest developments in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions 01 February — 31 March 2015, scheduled to be published in Volume 10 Issue 5 of Regenerative Medicine.
apceth
apceth (Germany; www.apceth.com) successfully completed the Phase I and initiated the Phase II part of its ongoing monocentric Phase I/II clinical trial TREAT-ME 1 with the engineered cell therapeutic product Agenmestencel-T, at the Klinikum Grosshadern in Munich. To the company’s knowledge, this is the first time that a genetically engineered MSC treatment has successfully completed a Phase I clinical trial and been approved to initiate a Phase II trial. The first patient in the Phase II trial has already been treated. The completed Phase I trial included six patients suffering from advanced-stage gastrointestinal adenocarcinomas (3 colorectal, 2 pancreatic, and 1 cholangiocellular carcinoma). Analysis confirmed that the infusion of the engineered cells and the treatment was safe and tolerable.
Asterias
BioTime’s (CA, USA; www.biotimeinc.com) subsidiary Asterias Biotherapeutics (MA, USA; www.ocata.com), announced today that Shepherd Center (GA, USA; www.shepherd.org), has commenced enrollment for the Phase 1/2a clinical trial of AST-OPC1 (oligodendrocyte progenitor cells) in newly injured patients with sensory and motor complete cervical spinal cord injury. The Phase 1/2a trial follows the successful completion of the Phase 1 trial run by Geron (CA, USA; www.geron.com), which met its primary endpoints of safety and feasibility when administered to five patients with neurologically complete, thoracic spinal cord injury. Shepherd Center was a site in the Phase 1 study and enrolled two of the five subjects in that study. Asterias intends to initiate enrollment for the Phase 1/2a trial at up to seven additional sites in the coming months. The Phase 1/2a clinical trial is designed to assess safety and activity of escalating doses of AST-OPC1 for complete cervical spinal cord injury. The trial will be an open-label, single-arm study testing three escalating doses of AST-OPC1 in patients with sub-acute, C-5 to C-7, neurologically complete cervical SCI. These individuals have essentially lost all sensation and movement below their injury site with severe paralysis of the upper and lower limbs. AST-OPC1 will be administered 14 to 30 days post-injury. Patients will be followed by neurological exams and imaging methods to assess the safety and activity of the product. The company plans to seek US FDA concurrence to increase the robustness of the proof of concept in the Phase 1/2a clinical trial by expanding enrollment from 13 patients to up to 40 patients. The company believes these changes will increase the statistical confidence of the safety and efficacy readouts, reduce the risks of the AST-OPC1 program and position the product for potential accelerated regulatory approvals. Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides US$ 14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT02302157).
BioLineRx
BioLineRx (Israel; www.biolinerx.com) announced successful top-line results from the Phase 1 safety and efficacy study of its lead clinical candidate, BL-8040, as a novel approach for mobilization and collection of bone-marrow stem cells from the peripheral blood circulation. All safety and efficacy endpoints were met, showing that treatment with BL-8040 as a single agent was safe and well tolerated at all doses and resulted in efficient stem cell mobilization and collection in all study participants. Importantly, the results support BL-8040 as one-day, single-dose collection regimen, which is a significant improvement upon the current standard of care. Robust stem cell mobilization was evident in all treated participants, across the different doses tested, supporting a novel approach to stem cell collection. After a single administration, BL-8040 enabled collection of a yield of stem cells that exceeds the number required to support a transplant in all treated participants, following only one collection procedure. BL-8040 is a short peptide, which functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. BL-8040 also mobilizes cancer cells from the bone marrow and may therefore sensitize these cells to chemo- and bio-based anti-cancer therapy. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.
Bone Therapeutics
Bone Therapeutics (Belgium; www.bonetherapeutics.com) announced that the first four patients in the phase IIA proof-of-concept study for spinal fusion procedures have been treated with Bone Therapeutics’ allogeneic osteoblastic cell therapy product, ALLOB®. This pilot Phase IIA study will enroll 16 patients with symptomatic degenerative lumbar disc disease who require interbody fusion surgery (a type of spinal fusion surgery that involves placement of fusion implants and bone grafts into the area between two vertebral bodies). Patients will be treated with a single dose of ALLOB® combined with bioceramic granules to achieve bone formation and fusion of the vertebral bodies. Safety and efficacy of this treatment will be assessed over 12 months, using clinical and radiological evaluation. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT02205138).
Cell Cure
BioTime’s (CA, USA; www.biotimeinc.com) subsidiary Cell Cure Neurosciences (Israel; www.cellcureneurosciences.com) opened the clinical trial of OpRegen® titled “Phase I/IIa dose escalation safety and efficacy study of human embryonic stem cell (hESC)-derived retinal pigment epithelium cells transplanted subretinally in patients with advanced dry-form age-related macular degeneration with geographic atrophy” at Hadassah University Medical Center in Jerusalem, Israel. Patient enrollment is expected to begin shortly. OpRegen consists of animal product-free retinal pigment epithelial (RPE) cells with high purity and potency. Cell Cure also announced that the option granted to Teva Pharmaceutical Industries (Israel; www.tevapharm.com) under a Research and Exclusive Option Agreement of October 7, 2010 to license-in rights to its OpRegen product has expired without having been exercised by Teva. Cell Cure will therefore be continuing the clinical development of OpRegen on its own and pursuing discussions with other potential strategic partners. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT02286089).
Cellerant
Cellerant Therapeutics (CA, USA; www.cellerant.com) announced that patient dosing has commenced in its multi-center, open-label, randomized controlled Phase 2 clinical trial of CLT-008, a first-in-class, allogeneic, cellular therapy, in de novo acute myeloid leukemia patients receiving induction chemotherapy. CLT-008 is a unique, off-the-shelf, cryopreserved, cell-based therapy that contains human myeloid progenitor cells derived from adult hematopoietic stem cells that have the ability to mature into functional granulocytes and platelets in vivo. Cellerant’s CLT-008 development program, including this Phase 2 clinical trial in AML patients, and the nonclinical studies required for approval in treating Acute Radiation Syndrome, is funded under a United States Government contract awarded on September 1, 2010 and valued at up to US$ 188 million. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT02282215).
NeuralStem
Neuralstem, Inc. (MD, USA: www. www.neuralstem.com) announced top line data from the Phase II trial of NSI-566 spinal cord-derived neural stem cells under development for the treatment of amyotrophic lateral sclerosis (ALS). The study met primary safety endpoints. The maximum tolerated dose of 16 million transplanted cells and the surgery was well tolerated. Secondary efficacy endpoints at nine months post-surgery indicate a 47% response rate to the stem cell treatment, as measured by either near-zero slope of decline or positive slope of ALS Functional Rating Scale (ALSFRS) score in seven out of 15 patients and by either a near-zero decline, or positive strengthening, of grip strength in seven out of 15 patients. Grip strength is an indicator of direct muscle strength of the lower arm. ALSFRS is a standard clinical test used to evaluate the functional status of ALS patients. The average ALSFRS score for responders at 9 months after treatment was 37. Non-responders scored an average of 14. These score represent 93%, versus 35%, of the baseline score retained, respectively, by the responders versus non-responders at 9 months, which is a statistically significant difference. As measured by an average slope of decline of ALSFRS, responders’ disease progression was -0.007 point per day, while non-responders’ disease progression was -0.1 per day, which was again statistically significant. Lung function as measured by Seated Vital Capacity shows that responder patients remained within 94% of their starting scores, versus 71% for non-responder patients. The trial met its primary safety endpoints. Both the surgery and cells were well tolerated, with one patient experiencing a surgical serious adverse event. Further information about this clinical trial are available at http://clinicaltrials.gov (ID: NCT01730716).
Ocata
Ocata Therapeutics (MA, USA; www.ocata.com), formerly known as Advanced Cell Technology (MA, USA; www.advancedcell.com), has completed dosing of its Phase 1/2 studies for dry age-related macular degeneration (dry AMD) and Stargardt’s Macular Degeneration. A total of 38 patients have been safely dosed. The 200,000 cell cohort, the highest level planned was successfully completed, paving the way for the next phase of the programs. Ocata previously announced that it has been granted Advanced Therapy Medicinal Product (ATMP) designation for its RPE therapy for macular degeneration. The SMD program has orphan status both in Europe and the US. Further information about these clinical trials are available at http://clinicaltrials.gov (ID: NCT01344993 and NCT01345006).