Industry Update: Regulations, approvals & acquisitions
Latest developments compiled from January 01 — February 28, 2017.
Latest regulations, approvals and acquisitions in the field of stem cell research and regenerative medicine compiled from publicly available information and press releases from non-academic institutions from January 01 — February 28, 2017, scheduled to be published in Volume 12 Issue 4 of Regenerative Medicine.
Regulations
US FDA
The US FDA (www.fda.gov) has unveiled a new designation category created as part of the 21st Century Cures Act to allow drugs to be eligible for designation as a regenerative advanced therapy (RAT). The stipulations for such a RAT designation include: “The drug is a regenerative medicine therapy, which is defined as a cell therapy, therapeutic tissue engineering product, human cell and tissue product, or any combination product using such therapies or products, except for those regulated solely under Section 361 of the Public Health Service Act and part 1271 of Title 21, Code of Federal Regulations; The drug is intended to treat, modify, reverse, or cure a serious or life-threatening disease or condition; and Preliminary clinical evidence indicates that the drug has the potential to address unmet medical needs for such disease or condition.” In terms of how to know if a company might qualify for such a designation, FDA points to its guidance on Expedited Programs for Serious Conditions — Drugs and Biologics, section III.A [1]. The guidance notes four other expedited designations: “Fast Track,” which includes actions to speed up development and review, “Breakthrough Therapy,” which features intensive guidance on efficient drug development, “Accelerated Approval,” which is based on “an effect on a surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict a drug’s clinical benefit,” and “Priority Review,” which shortens the review clock from 10 months to six months. The request for RAT designation must be made either concurrently with submission of an Investigational New Drug application (IND) or as an amendment to an existing IND.
Green light
BioRestorative
BioRestorative Therapies (NY, USA; www.biorestorative.com) has received a green light from US FDA to start a Phase 2 clinical trial assessing lead product candidate BRTX-100 for the treatment of lower back pain caused by protruding/bulging discs due to degenerative disc disease. The 72-subject randomized, double-blind study will evaluate the safety and efficacy of a single dose of the cell therapy injected directly into the affected disc. BRTX-100 is a product formulated from autologous cultured mesenchymal stem cells (MSC) collected from the patient’s bone marrow. BRTX-100 production process involves collecting a patient’s bone marrow, isolating and culturing stem cells from the bone marrow and cryopreserving the cells. In an outpatient procedure, BRTX-100 is to be injected by a physician into the patient’s damaged disc.
Cellectis
Cellectis (France; www.cellectis.com), a biopharmaceutical company focused on developing immunotherapies based on gene edited CAR T-cells (UCART), has received an Investigational New Drug (IND) approval from the US FDA to initiate Phase 1 clinical trials of UCART123 the Company’s most advanced, wholly owned TALEN® gene edited product candidate in patients with acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm. UCART123 is a gene edited T-cell investigational drug that targets surface antigen CD123.
Cell Medica
Cell Medica UK; www.cellmedica.co.uk) has received from US FDA a Fast Track designation to its lead oncology product CMD-003 for patients with relapsed/refractory lymphoma and post-transplant lymphoproliferative disease associated with the oncogenic Epstein Barr virus (EBV). CMD-003, also known as baltaleucel-T, is an investigational therapy in which the patient’s T cells are activated to kill malignant cells expressing EBV antigens. The product has the potential to address a range of EBV-associated lymphomas, nasopharyngeal carcinoma and gastric cancer. The FDA Fast Track designation follows Orphan Drug Designations from both the FDA (EBV-associated non-Hodgkin lymphoma) and European Commission (extranodal NK/T lymphoma, nasal type and post-transplant lymphoproliferative disease).
Fibrocell
Fibrocell Science (PA, USA; www.fibrocell.com) announced that the US FDA has granted Fast Track designation to FCX-007 for the treatment of Recessive Dystrophic Epidermolysis Bullosa (RDEB). Fibrocell, in collaboration with Intrexon (VA, USA; www.dna.com), is currently investigating FCX-007 in a Phase 1/2 trial for the treatment of RDEB. It was previously granted Orphan Drug designation for the treatment of Dystrophic Epidermolysis Bullosa and Rare Pediatric Disease designation for RDEB. FCX-007, a genetically-modified autologous fibroblast that encodes the gene for COL7, is being developed as an injectable for direct administration to the affected areas, thus avoiding systemic distribution.
GtreeBNT and RegeneRx
GtreeBNT (Korea; www.gtreebnt.com) has received permission from the US FDA to conduct a Phase 3 trial of RGN-137 – licensed from RegeneRx Biopharmaceutical (MD, USA; www.regenerx.com) – for epidermolysis bullosa (EB) in the US. RGN-137 is a dermal would healing gel that incorporates thymosin beta 4 as an active pharmaceutical ingredient which accelerates wound healing, reduce inflammation and induce regeneration to promote tissue integrity throughout the body that is defective in patients with EB. RGN-13 previously received orphan designation for EB from the US FDA.
Japan
The government-affiliated Riken Research Institute in Kobe (www.kobe.riken.jp/en), Kyoto University (www.kyoto-u.ac.jp/en), Osaka University (www.osaka-u.ac.jp/en) and the Kobe City Medical Center General Hospital (www.chuo.kcho.jp) have received a green light from the Japanese Ministry of Health, Labour and Welfare (www.mhlw.go.jp/english/) on a regenerative treatment that utilizes donated iPSC, which will likely reduce the cost and time of the procedure by about 90%. The ministry determined that the proposed clinical research satisfied safety requirements. Kyoto University will provide Riken with the iPS cells that will be grown into retinal cells. Osaka University and the Kobe medical center will perform the surgeries. A solution containing the retinal cells will be injected into the back of the patients’ eyes. In 2014, Riken and others performed the world’s first retinal transplant treating age-related macular degeneration with iPSC. Those cells came from the patient’s body. The process cost roughly US$ 881,000 (¥100 million), which included tests for cancer. The approximately 10-month preparatory period was also seen as a barrier to widespread adoption.
Vericell
Vericel (MI,USA; www.vcel.com has announced that the US FDA has designated the investigation of ixmyelocel‘T for reduction in the risk of death and cardiovascular hospitalization in patients with chronic advanced heart failure due to ischemic dilated cardiomyopathy as a Fast Track Development Program. The Fast Track program is an expedited drug development and review program for new drugs or biologics intended to treat serious or life-threatening conditions that demonstrate the potential to address an unmet medical need. Ixmyelocel-T is an investigational autologous expanded multicellular therapy manufactured from the patient’s own bone marrow using Vericel’s proprietary, highly automated, fully closed cell-processing system. This process selectively expands the population of mesenchymal stromal cells and alternatively activated macrophages, which are responsible for production of anti-inflammatory and pro-angiogenic factors known to be important for repair of damaged tissue. Ixmyelocel-T has been designated as an orphan drug by the U.S. Food and Drug Administration for use in the treatment of dilated cardiomyopathy.
ViaCyte
ViaCyte (CA, USA; www.viacyte.com) and Beyond Type 1 (CA, USA; www.beyondtype1.org) a not-for-profit advocacy and education group for those living with type 1 diabetes, have announced a grant from Beyond Type 1 to support ViaCyte’s efforts to develop a functional cure for type 1 and other insulin-requiring diabetes.
ViraCyte
ViraCyte (TX, USA; www.viracytellc.com) has announced that the US FDA has granted Fast Track designation for Viralym-C, ViraCyte’s T cell immunotherapy product designed to treat refractory cytomegalovirus infections in patients following a stem cell transplant (www.clinicaltrials.gov ID: NCT02313857www.clinicaltrials.gov ID: NCT02313857).
Pending
BrainStorm
BrainStorm (Israel; www.brainstorm-cell.com) had signed an agreement with the Centre for Commercialization of Regenerative Medicine (CCRM; ON, Canada; www.ccrm.ca), a not-for-profit organization that supports development of regenerative medicine, to support a market authorization request for its Amyotrophic Lateral Sclerosis treatment, called NurOwn®. NurOwn technology takes MSCs and, by growing them in proprietary conditions, converts them into biological factories secreting a variety of neurotrophic factors. CCRM is helping BrainStorm meet requirements for the Canadian health regulator’s early access pathway, which provides rapid review for drugs to treat serious or life-threatening conditions.
Kite
Kite Pharma (CA, USA; www.kitepharma.com) has submitted an Investigational New Drug (IND) application with the US FDA to initiate a Phase 1 trial of KITE-718, a T cell therapy engineered to express T cell receptors (TCRs) that target MAGE A3 and MAGE A6. MAGE A3/A6 are frequently found in common tumors including bladder, esophageal, head and neck, lung and ovarian cancers. KITE-718 recognizes the MAGE A3 and MAGE A6 fragments bound to a Class II HLA (DPB1*04:01) and therefore has the potential to kill tumor cells both directly and indirectly through activation of the immune system given it incorporates a class II TCR. Class II HLA (DPB1*04:01) is found in 50 percent to 70 percent of Caucasians. The trial is designed to assess the safety and anti-tumor effect of KITE-718 on these solid tumors.
Acquisitions
Allergan and LifeCell
Acelity (TC, USA; www.acelity.com) has completed the sale of its regenerative medicine business unit, LifeCell Corporation and each of LifeCell’s subsidiaries, to Allergan (NJ, USA: www.allergan.com) for US$ 2.9 billion in cash. LifeCell’s regenerative medicine and reconstructive surgery portfolio will be combined with Allergan’s portfolio of medical aesthetics, breast implants and tissue expanders, enhancing the potential for continued long-term growth.
Cytori and Azaya
Cytori Therapeutics (CA, USA; www.cytori.com) has acquired certain assets from privately held Azaya Therapeutics (TX, USA). The acquisition would provide Cytori with a proprietary liposomal nanoparticle technology platform that would expand and complement the Company’s position in regenerative medicine market.
References
[1] Food and Drug Administration. Center for Drug Evaluation and Research. Guidance for industry. Expedited programs for serious conditions — drugs and biologics (2014).