Some countries in Europe and elsewhere are looking ahead for opportunities that might emerge from the recent public policy change in the United States that allows federal funding of embryonic stem cell research. Industry experts expect the stem cell industry to flourish in the favorable environment they see developing.

The National Institutes of Health (NIH) set July 7 as its target date for finalizing its Draft Guidelines for Human Stem Cell Research, although no major changes are anticipated.

The draft was released for public comment after the President issued an order in March that reversed a prior ban restricting federal funding for embryonic stem cell research.

The guidelines discuss acceptable use of stem cells derived from embryos created by in vitro fertilization (IVF) for reproductive purposes and no longer needed for those purposes. According to the NIH, the guidelines will try to ensure that such use is “ethically responsible, scientifically worthy, and in accord with applicable law.” The guidelines also describe the conditions and informed consent procedures required during the derivation of such embryonic stem cells.

Despite the delays that could result, however, overseas businesses with which LSL talked about the new U.S. policy are optimistic about its potential spin-off effects. Scotland-based Angel Biotechnology plc, a contract manufacturer, has been involved in the GMP manufacture of cell-based therapies and stem cells since 2005. Angel’s COO, Gordon Sherriff, forecasts that “commercially, whatever the changes, the removal of those barriers will benefit Europe and elsewhere.” The size of the U.S. market gives it the technology and money to fund research culminating in a commercial product, he said. “The change will prompt investors to start putting money into the stem cell industry,” said Sherriff.

When Georgia-based Aderans Research Institute (ARI) needed product manufactured for use in a recently completed Phase I clinical study conducted in the United Kingdom, Angel provided GMP manufacturing services for an autologous cell treatment. UK-based ReNeuron, another Angel client, recently gained approval from the MHRA (Medicines and Healthcare Product Regulatory Agency) to conduct a clinical trial using expanded neural stem cell therapy for treatment of patients left disabled by an ischemic stroke. Angel will manufacture the therapeutic ReN2001 cells, which have the potential to restore lost brain tissue.

“Every product that comes through has to be treated as an individual product, and the manufacturing process is very particular depending on where the product is to be finally distributed,” noted Angela Scott, Angel’s director of operations, referring to different countries’ regulatory requirements.

Hiram Chipperfield, Ph.D., of ERA Consulting Ltd. in London, which also has an international clientele, says the firm has an increasing number of cell therapy clients who seek assistance in matters of regulatory affairs and product development. Chipperfield agrees that as more U.S. companies enter the embryonic stem cell area, companies in the United Kingdom and all of Europe might attract more funding.

Chipperfield, who is ERA’s regulatory affairs project manager, referred to the differing regulations among European countries as “a patchwork.” At one end of the spectrum, the United Kingdom allows a lot of embryonic stem cell research, and also embryo research as long as it is properly licensed and regulation-compliant. Germany is one of the countries at the opposite end, having made it a criminal offense to create a new embryonic stem cell line, notes Chipperfield. In between the two extremes, there are variations by country; in some, no embryonic stem cell regulation exists.

Unlike basic research, cell therapies are governed by the European Medicines Agency (EMEA) of the EU, which makes no distinction between embryonic and other stem cells. Chipperfield said that a therapy derived from embryonic stem cells would, therefore, be approved Europewide, but that no such therapy has been approved to date.

HUMAN CLINICAL TRIALS BEGIN
In the United States, the first embryonic stem cells clinical trial in humans has been cleared by the FDA and is set to begin this summer. California-based Geron, the trial’s sponsor, said it planned to enroll 8-10 patients in the Phase I study to assess the safety of its therapy, GRNOPC1, being studied for patients with acute thoracic spinal cord injury. In announcing the trial’s clearance, Geron’s CEO, Thomas Okarma, M.D., Ph.D., stated that the potential product could mark the beginning of a new chapter in medical therapeutics — one that reaches beyond pills to a new level of healing — the restoration of organ and tissue function achieved by the injection of healthy replacement cells.

Despite NIH funding restrictions, U.S. research activities with embryonic stem cells have been ongoing, financed by private and state government sources. The California Institute of Regenerative Medicine (CIRM) recently granted two awards totaling $6.2 million to San Diego-based Novocell for research using human embryonic stem cell-derived pancreatic cells for diabetes cell therapy.

GOVERNMENT FUNDING IS NOT KEY TO PROGRESS
A total of 2,147 clinical trials (Phase I-IV) for stem cell therapies overall were listed, as of June, on NIH’s website: www.ClinicalTrials.gov. Many of the studies utilize adult stem cells, a second type of stem cells used in therapies, which can serve as a repair system for the body and have the potential to develop into many different types of body cells.

In its clinical trial underway, New Jersey-based Celgene Cellular Therapeutics (CCT) is testing an immunomodulatory therapy, PDA001, which uses human placenta-derived stem cells to treat patients with Crohn’s disease. It is the first study to use placenta-derived stem cells for the repair of damaged or diseased tissue and is currently completing the Phase I stage of development.

Of NIH’s new policy, CCT’s CEO, Robert Hariri, M.D. says the change will have “no impact” on the progress of turning stem cells to medicine. “What is driving progress is not government funding of one type of technology or another,” he continued. “It’s the investment by industry in doing the essential clinical testing that is necessary,” he said, emphasizing that the translational part of the equation is what is important. “Over the past 10 years, companies have invested hundreds of millions of dollars in creating the processes and support technologies to identify the cells that are clinically useful,” continued Hariri, “and then to come up with methods to deliver them to patients as pharmaceuticals.”

Hariri notes that while embryonic stem cells are an interesting platform to do research, from which much has been learned, there are fundamental deficiencies in embryonic stem cells and problems with their stability “that may take decades to work through.” Alternatively, there are proven platforms that derive stem cells from other sources, which have been used in thousands of patients.

Doctors have used blood-forming stem cells in bone marrow transplants — from the patient himself or a donor — for more than 40 years. They are used to reconstitute one’s immune system after leukemia lymphoma, or after various blood or autoimmune disorders have been treated with chemotherapy.

Michael Werner, Esq., a partner in the Washington, D.C. law firm Holland & Knight (and former chief policy officer at the Biotechnology Industry Organization [BIO] trade group), holds a contrasting opinion, viewing the ban removal as “very important,” based on his background in regenerative medicine, which includes stem cells and other technologies to repair or replace damaged cells, tissues, or organs. “We need to have basic research to advance the technology; we need to have the imprimatur of the NIH that this is important research,” emphasizes Werner. “You need to have more information so when the FDA makes decisions on safety and efficacy, they [the reviewers] have case studies on the technology.” He adds that the previous ban meant that during that period other countries developed the infrastructure to do the work, their scientists became more expert in the technology.

Looking ahead, Werner is confident that, despite the “lost time,” the United States will devote sufficient resources to stem cell research, and “because of the nature of our industry here, we will be able to catch up.” Meanwhile, other countries will be watching for signs of U.S. progress and will be on the lookout for opportunities that may accompany it.