EU Workshop Report on Authorization of Advanced Therapy Medicinal Products
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The European Medicines Agency (EMA) published a report from a multi-stakeholder expert meeting held in May exploring ways to foster the development of ATMPs in Europe and expand patients’ access to these new treatments.
ATMPs comprise gene therapies, tissue-engineered products, and somatic cell therapies. These medicines have the potential to reshape treatments of a wide range of conditions, particularly in diseases for which conventional approaches are inadequate. However, eight years since EU legislation on ATMPs went into force, only five ATMPs are currently authorized. At the same time, clinical trials investigating ATMPs are a fast-growing field of interest, underlining the need to better support innovation through a coherent and appropriate regulatory environment.
“We have organized this meeting with all relevant stakeholders to discuss concrete proposals on how we can nurture a regulatory environment that encourages development of ATMPs, safeguards public health and, ultimately, facilitates timely access for patients to much needed treatments,” said EMA’s executive director Guido Rasi in his opening address.
The meeting brought together leading academics and researchers, representatives from patients’ and healthcare professionals’ organizations, small and large pharmaceutical companies, the investment community, incubators and consortium organizations, health technology assessment (HTA) bodies, national competent authorities, and the European Commission. In their discussions, they focused on four key areas:
- Facilitating research and development
- Optimizing regulatory processes for ATMPs
- Moving from hospital exemption to marketing authorization
- Improving funding, investment, and patient access.
Ideas and solutions proposed by the different stakeholders are summarized in the meeting report. Some of the recurring themes include the need for early interaction and guidance from regulators, more transparency and information sharing, greater harmonization between Member States on various aspects of the ATMP legislative framework, and measures to tackle inequalities in patient access to ATMP treatments.
EMA and its scientific committees, together with the European Commission and the national competent authorities, are discussing the proposals made during the meeting. Concrete actions will be determined over the next few months and shared with stakeholders.
Zika and the Need for a Global Strategy Against Mosquito-Borne Diseases
Developing a protective vaccine against the Zika virus is only one step in providing a long-term solution to the disease, and should be viewed in the context of tackling all mosquito-borne diseases, according to research and consulting firm GlobalData. The company’s latest analysis covering the endemic, “The Zika Virus: An Update on the Outbreak and the Fight Against It,” states that the uncertainty around the virus has brought Flaviviruses to the world’s attention. This opportunity should be used not only to develop a vaccine specifically protecting against the Zika virus, but to formulate a global strategy against mosquito-borne diseases. The Zika virus is transmitted by the Aedes aegypti species of mosquito.
Mirco Junker, GlobalData’s analyst covering infectious diseases, says: “The Zika virus is a member of the genus Flavivirus, a group of single-stranded RNA viruses that also includes dengue, West Nile, yellow fever, Japanese encephalitis, and chikungunya virus, all of which are transmitted by mosquitoes. Approaches to combating the vector instead of the virus include the prevention of vector reproduction through limiting breeding grounds, insecticides, direct genetic manipulation, or the use of bacteria, ultimately leading to the demise of the mosquitoes.”
In terms of potential vaccines, the vast majority of Zika vaccine products are currently in early preclinical trials. It will take many years until one of them receives market approval. For pharmaceutical companies, developing vaccines is a difficult and resource-intensive process.
Junker continues, “The majority of companies that have entered the race are smaller biotech companies with limited resources, whereas the large pharmaceutical companies — including GlaxoSmithKline, Johnson & Johnson, Merck, Pfizer, Sanofi, and Takeda — are currently evaluating only how their abilities and experiences can help in the fight against Zika. Vaccines are based on biological agents that require stringent establishment of lot-to-lot consistency and stability. From a scientific perspective, it is also not yet clear which vaccine strategy will ultimately lead to a protective vaccine. These complicating factors highlight the need for more collaboration between the companies themselves, as well as support from governmental organizations in identifying the most promising vaccine candidates and bringing them to the market.”
Robust Pipeline of Stem Cell Therapies Faces Commercial Challenges
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According to business intelligence provider GBI Research, a number of obstacles remain before stem cell therapies can become widely commercially viable. That is despite the significant driving factors for growth, steady progress in clinical research, and increasing evidence of product effectiveness. In a July 2016 report (Stem Cell Therapies: Global Trends in the Competitive, Technological, and R&D Landscape) GBI states that the pipeline as a whole is relatively large, with 330 products in active development. R&D is gaining momentum as candidates move into clinical trials and the results demonstrate therapeutic potential.
GBI managing analyst Rodrigo Gamboa says that stem cells provide therapeutic potential for indications in which current pharmacological and surgical treatment options are ineffective. But a significant divide remains between the number of therapeutic applications currently available for patients and the number of research programs investigating broader medical applications.
“Stem cells are currently used for a modest variety of indications,” Gamboa says, “with skin and blood stem cells representing the majority of therapeutic uses. The industry is pursuing a broad base of therapeutic applications, which is evident in R&D efforts observed in the sector.” More than 15 therapeutic areas are targeted by the industry’s more than 1,000 clinical trials.
Despite promising recent technological developments, converting scientific potential into real therapeutic value is not straightforward. According to a GBI Research survey, the stem cells field faces obstacles including research expenses, which survey participants called the biggest factor limiting their progress.
“Manufacturers will need to adopt novel strategies to realize their full potential,” Gamboa concludes. “It is likely that manufacturing methodologies will use partly or fully automated systems in future approaches to improve yield, purity, and cost-effectiveness.” He cites progress made by companies such as Cynata Therapeutics, which is implementing innovative biomanufacturing methods to generate robust, consistent, and inexpensive stem cells. “Such companies are pointing towards a promising outlook in this regard.”
Top Three Account for 68% of Pharmaceutical Industry Pipeline
The top three therapy areas — oncology, infectious diseases, and central nervous system (CNS) disorders — accounted for a combined 68% of the overall pharmaceutical industry pipeline in the first quarter of 2016, according to business intelligence provider GBI Research. The company’s Innovation Tracking Factbook 2016: An Assessment of the Pharmaceutical Pipeline states that oncology is by far the largest therapy area, with almost 7,000 products in active development, almost matching the combined size of infectious diseases and CNS disorders, which each have over 3,000 products in active development. Also, there is a great deal of pipeline activity in the following areas, with immunology, metabolic disorders, and cardiovascular diseases each having pipelines consisting of over 1,000 products.
Dominic Trewartha, managing analyst for GBI Research, says: “The pipelines in these therapy areas are the largest because they have substantial patient populations and strong unmet needs.” He said that oncology is a rapidly growing therapy area, with the largest three indications in terms of the number of products being breast, lung, and colorectal cancer — each exhibiting pipeline growth in excess of 15%.
GBI Research’s report also states that the overall pharmaceutical industry pipeline increased by 5% in early 2016. This trend generally holds true across all therapy areas, with only CNS disorders and immunology having marginally decreased in size. The most rapid growth was witnessed in the smallest therapy areas, led by women’s health, which grew by 55% in the same time period.
Trewartha concluded, “Virtually all therapy area pipelines increased in size in Q1 2016 and within certain therapy areas, particularly in oncology. The majority of major indications have seen their pipelines increase in size since 2015. Although the majority of these pipeline products are at an early stage of development, meaning their safety and efficacy profiles are generally unproven, the large overall pipeline size demonstrates that there is likely to be a steady stream of incremental and breakthrough innovation that reaches the various disease markets in the foreseeable future.”
China Seen As Fastest Growing Market
Partnerships in the Biologics Market: In June, CPhI Worldwide conference announced findings of its latest “Pharma Insights” report on the Chinese drug market. Released at CPhI China 2016 in Shanghai, it demonstrates strong confidence in the expanding Chinese market among international companies. Of those surveyed, 85% believe that China will have the fastest growing biologics sector over the coming decade, and 65% predict that patented new chemical entities (NCEs) will be discovered and developed within the country in as little as five years. A growing biotechnology and R&D industry is heavily supported by the Chinese government.
Big pharma and generic manufacturers are increasingly seeking access to the Chinese market through partnerships, with 74% of international companies planning to “increase or initiate partnership with local companies.” Both international and Chinese companies are seeing natural synergies. Local companies benefit from increasing their knowledge of advanced technologies; foreign companies benefit from market access through partners who are familiar with its complexities. Such arrangements will proliferate over the next few years. Most (90%) Chinese domestics are searching for international partners.
Over half of the domestic respondents believe that “the Chinese manufacturing sector will advance its manufacturing capabilities in complex formulations and biologics to levels comparable to those in the West within the next three to five years.” Emphasizing a shift toward developing higher manufacturing and regulatory standards, over 60% of Chinese companies surveyed already are implementing good manufacturing practice (GMP) standards, 40% quality by design (QbD), 40% continuous improvement, and nearly 20% either six-sigma or operational excellence programs.
International companies share a renewed confidence in China’s improving standards, with over 50% stating that they believe “commercial manufacturing can be competently outsourced within China.” Nearly 30% believe both contract manufacturing activity and clinical drug supply and formulation services can be competently undertaken by Chinese companies. Some 27% even believe that US and European drug supplies could come from China.
The report concludes that the chief driving force behind rising standards within the Chinese market has been an increased awareness among its domestic consumers and their desire for more tightly regulated, higher quality drugs. Chinese companies are investing for the future: 21% in cold-chain storage technology, 16% in antibody–drug conjugate (ADC) development, 43% in commercial and scale-up facilities, and 27% in continuous processing. The latter is predicted to revolutionize biomanufacturing over the next decade. Its initial costs are high, however, implying a significant change in approach from some Chinese companies.
The report identifies two major “drag factors.” First, solid-dose products are lagging behind the biologics sector, and China may have already lost too much ground to the Western and Indian manufacturers that lead the sector internationally. And as China’s overall drug market expands, its Food and Drug Administration (CFDA) is experiencing increased backlogs and regulatory bottlenecks. The domestic industry strongly supports implementation of US-style user fees to alleviate those pressures, with 94% stating that “the CFDA must grow rapidly to a comparable size to the US Food and Drug Administration (FDA) if it is to properly regulate its industry.”
The report draws a picture of a very different Chinese drug market in five years. That includes generics and active pharmaceutical ingredients (APIs) exported in large numbers, as well as a well-established biologics and research industry and multinational contract manufacturers. In less than a decade, there could be new drugs that have been researched, clinical-trial manufactured, tested, and distributed by Chinese companies specifically for local patient cohorts.
Overall, confidence in China’s short-term growth remains extremely high, with 25% of domestic companies believing China soon will be the world’s top biopharmaceutical innovator. Nearly half believe that future biologic sales in China will be led by international exports.
Meanwhile, most international companies are forecasting explosive growth as China’s healthcare system evolves. Not only do 60% of foreign organizations already in China project their sales to grow by more than 25%, but 15% even predict growth of 200% or more over the next five years. Similarly, over 70% of Chinese companies are either “confident” or “extremely confident” in the sustained buoyancy of the Chinese market, and 65% of them expect growth ~20% in the next year alone. A further 26% anticipate growth at 20–40%, with 8% expecting to double in size. So despite a recent, relative slow-down in the overall Chinese economy, the country’s pharmaceutical sector remains buoyant.
“This report mirrors our experiences on the ground during CPhI China 2016,” says Chris Kilbee (group pharma director at UBM EMEA), “where there was clear confidence in future prospects from both international and domestic companies. What is noticeable is a renewed commitment to investing for longer-term growth, with partnerships and manufacturing deals becoming increasingly ambitious. The API and generic market will remain extremely strong, and biologics investment and production will proliferate. Our research suggested that within five years China will be challenging on a number of fronts — with international CMOs and perhaps even locally researched and developed NCEs. This year, we have seen a considerable expansion of CPhI-China event to 35,000 attendees (an increase of 5,000), and we are looking to grow alongside the Chinese pharma economy.”