Teeing up the World Stem Cell Summit’s discussion of global regenerative medicine trends, Mike Druckman, U.S.-based partner in the Hogan Lovells pharmaceuticals & biotechnology regulatory practice area, served as the moderator and invited each panelist to summarize the hot topics in each of their jurisdictions, emphasizing how these advanced medicinal therapies carry unique legal challenges. The panel then went on to discuss three evolving arenas that are critical for regenerative medicine companies to understand: clinical trials regulations, reimbursement issues, and the marketing of unapproved therapies.
Clinical trial issues
Opening up the conversation surrounding clinical trial issues, Mandi Jacobson, Sydney-based partner in the Hogan Lovells medical devices and technology regulatory practice group, pointed out that a lack of manufacturing capacity is presenting challenges for makers of regenerative medicinal therapies in Australia. Nevertheless, Ms. Jacobson added, there have been 322 regenerative medicine clinical trials in Australia in the past six years, with 133 still ongoing, and gene therapy being the most common type of regenerative medicine product tested. These trials have been focused on the oncology and central nervous system spaces. Ms. Jacobson predicted there would continue to be sizable growth in this clinical trials market.
Mikael Salmela, Paris-based partner in the Hogan Lovells strategic operations, agreements & regulation (SOAR) practice group, summarized how there have been many clinical trials ongoing in Europe in this space as well. Mr. Salmela explained how despite this growth, the European regulatory framework for advanced therapeutic medicinal products (ATMPs) has not kept pace with scientific developments. For instance, human cells may be regulated as either “tissue” or as “blood,” and this classification may vary across countries in the EU, which can create issues for collection centers. In addition, EU data protection and privacy rules often create issues for health institutions. Further, Mr. Salmela said, EU good clinical practices (GCP) and good manufacturing practices (GMP) regulations contain specific requirements for companies operating in the EU, and firms doing business in Europe will often need to educate their contracting partners about these rules in order to ensure compliance.
Continuing the panel’s discussion of compliance issues, Lowell Zeta, U.S.-based partner in the Hogan Lovells pharmaceuticals & biotechnology regulatory practice area, highlighted manufacturing issues that occur at early stages for developers of regenerative medicines. Mr. Zeta described how the industry is seeing a greater emphasis on standardizing protocols at these early stages, including validating methods and processes to gear up for tech transfer to contract manufacturers, and to allow for better comparability analyses. Mr. Zeta emphasized how continuous manufacturing (CM) processes can advance drug quality, reduce drug shortages, and potentially lower the time it takes for products to come to market. Mr. Zeta also advised that the success of personalized medicine may depend on valid and accurate companion diagnostics.
Shifting the conversation to issues surrounding payment and reimbursement for regenerative medicines, Charlotte Damiano, Paris-based partner in the Hogan Lovells health practice group, summarized how the French government has considered favoring gene therapies with rapid market access. However, the French government has become stricter with the requirement for comparative data, and rejected indirect data, Ms. Damiano explained. Further, although the French authorities have shown a willingness to negotiate outcome-based pricing agreements for regenerative medicines, Ms. Damiano cautioned that these arrangements are difficult to reach in practice. In addition, the French government has recently asked manufacturers of gene therapies to cut their prices, further demonstrating the need for regulatory assistance in bringing ATMPs to market in France.
Meanwhile in the U.S., James Huang, Washington, DC-based counsel in the Hogan Lovells health practice group, explained that there is a patchwork of different health care payment systems, with a myriad of payers ranging from governmental agencies to private entities – and transformational medicines are challenging those payers and payments systems, he said. However, Mr. Huang observed that we have begun to see novel reimbursement pathways targeting regenerative medicines in the U.S. For example, in 2020, Medicare developed a special payment pathway for CAR-T cell therapies. Nevertheless, numerous open questions remain regarding reimbursement for novel regenerative medicines in America, Mr. Huang noted, pointing out that the manner in which payers classify, cover, and reimburse for these types of products can vary a great deal. Mr. Huang thus advised that early engagement — especially with major U.S. payers, like the Medicare program —can be critical for the success of a regenerative medicine sponsor.
Turning to payment for regenerative medicines in China, Lu Zhou, Beijing-based partner in the Hogan Lovells corporate & finance practice group, spotlighted competition for international companies to be added to the National Reimbursement Drug List, which allows companies access to the vast majority of the Chinese population. China’s regulators will typically demand manufacturers to cut their drug prices by up to 50 percent in the course of negotiating entrance into the drug list. There are currently only two domestic CAR-T cell therapy products approved to be marketed in China. However, they have not been included in the drug list, meaning CAR-T cell therapy products cannot be reimbursed by China’s public health system at this stage, and must be paid out of the patient’s own pocket, or covered by private insurance. Therefore, Ms. Zhou concluded, entrance into China’s health care market requires companies to weigh the potential loss of profit margins against the potential increase in volume of sales.
Continuing the panel’s discussion of issues facing regenerative medicine firms in China, Carol Shao, Beijing-based associate in the Hogan Lovells corporate & finance practice group, explained how drugs cannot enter the Chinese market until they are approved by the National Medicinal Products Authority (NMPA). Ms. Shao outlined one exception to this general rule, summarizing how Chinese regulators have provided a special pathway for unauthorized drugs to be imported and marketed in one part of the Hainan province - Boao Medical Pilot Zone. Foreign manufacturers of regenerative medicine which have already obtained the special importation and marketing approval in Boao may apply for a real world data (RWD) research pilot in Boao for use of such drug in order to generate RWD which could then turn into real world evidence to the benefit of subsequent product registration with the NMPA, Ms. Shao added.
Closing the conversation, Ernesto Algaba, Mexico City-based partner in the Hogan Lovells pharmaceuticals & biotechnology regulatory practice group, similarly described that as a general rule only drugs approved by the national regulator may be lawfully sold in Mexico. However, that there is a wide field for using and developing regenerative therapies and related drugs through the carrying out of clinical trials, he explained. Given the particularities of the Mexican population and a diversified spectrum of health institutions, there has been a trend toward carrying out research activities in Mexico. Mr. Algaba emphasized the importance of whether Mexico classifies a medicinal product as a “biologic” or as a “transplant.” In addition, Mr. Algaba spotlighted regulations in Mexico related to informed consent and data privacy. Further, given the geographical location of Mexico, medical tourism activities have also increased there in relation to regenerative medicine.
You can view video recordings and summaries of the other panels from the World Stem Cell Summit online here:
This article is the twelfth in our 2022 series, “Trends in Cell, Tissue, and Gene Therapies,” which aims to help you stay informed about the broad array of legal and regulatory issues affecting companies operating in the regenerative medicine space. From clinical studies, to obtaining patents, to scaling up manufacturing, our global team will discuss novel issues arising in all parts of the world, including unique deal-making, litigation, and inspections concerns for CTGT companies.