Spotlight May 2016

BPI Staff

May 11, 2016

12 Min Read



Niche Disease: Autoimmune/Noninfectious Uveitis

Uveitis is the inflammation of the uvea, the pigmented layer that lies between the eye’s inner retina and its outer fibrous layer composed of the sclera and cornea. The most frequent etiologies are autoimmune diseases such as Behçet disease. Noninfectious intermediate and posterior uveitis (NIU) represents 10–15% of uveitis cases, making it the fourth leading cause of blindness in the developed world. About one in 4,500 patients suffer with this condition. Uveitis typically has been treated with glucocorticoid steroids. But every year, an estimated 30,000 US and EU patients with autoimmune uveitis are refractory to approved treatments. If the condition goes untreated, serious complications including blindness can result.

Organizations: One support group is the Ocular Immunology and Uveitis Foundation ( Its mission is to find cures for ocular inflammatory diseases, to correct the worldwide deficit of properly trained ocular immunologists, and to provide education and emotional support for patients afflicted with ocular inflammatory disease.

Treatments in Development: In the European Union, orphan drug designation is granted by the European Medicines Agency (EMA) to drugs or biologics that treat life-threatening or chronically debilitating rare diseases affecting fewer than five in 10,000 individuals. In the United States, the US Food and Drug Administration (FDA) defines a rare disease as affecting fewer than 200,000 people. Products receiving orphan drug designation receive market exclusivity for up to 10 years in Europe as well as development incentives such as regulatory and protocol assistance. The US designation gives seven years of market exclusivity and incentives including federal grants and tax credits.

In September 2015, TxCell SA (Nice, France) was granted US Orphan Drug Designation for its candidate cell therapy treatment of chronic non-infectious uveitis. Col-Treg cells are a personalized T-cell immunotherapy product based on the properties of autologous collagen-II–specific regulatory T lymphocytes. After intravenous administration, Col-Treg cells home into the site of inflammation, where they are activated by a specific antigen. The cells then act by locally releasing immune-suppressive factors, cell–cell interactions, and cytotoxic activity to treat the inflammation. Classified as an advanced therapy medicinal product (ATMP) by the European Medicines Agency (EMA), this cell therapy now has both EU and US orphan drug designations. A first-in-man clinical study is planned to start in 2016.

In February 2016, the EMA granted orphan drug designation for treatment of refractory NIU to EYS606 gene therapy, in development at Eyevensys (Paris, France). This combination product consists of a plasmid encoding for a soluble tumor necrosis factor (TNF) receptor delivered by means of a high-precision electro-transfection-injection system (ETIS). That accurately injects the plasmid into the ciliary muscle cells of a patient’s eye. EYS606 has demonstrated high efficacy, safety, and long-lasting effects in a number of animal models. It leads to sustained expression of therapeutic agents in their eyes over extended periods, which alleviates the pain of repeated invasive administrations. Eyevensys plans to start a clinical trial in 2016 as well.

AbbVie Joins Dementia Consortium

The Dementia Consortium is a global £4 million collaboration among academia, charity, and the private sector formed to seek new drug treatments for dementia. In February 2016, AbbVie Inc. joined medical research charities MRC Technology and Alzheimer’s Research UK (the UK’s leading dementia research charity) as a new pharmaceutical partner alongside Astex Pharmaceuticals, Eisai Co. Ltd., and Eli Lilly and Company. AbbVie brings additional expertise, resources and capital to the consortium, allowing for more projects to be funded and treatments developed. Its own mission is to develop and market advanced therapies for some of the world’s most complex and serious diseases.

Simon Ridley, director of research at Alzheimer’s Research UK, welcomed the new partner, saying AbbVie strengthens the consortium’s ability to accelerate the search for effective new treatments for dementia. “To find new treatments for neurodegenerative diseases, we need to explore as many different approaches as possible. Our growing range of pharma partnerships will ensure that we can continue to invest in a diverse range of projects to build drug discovery pipelines.”

To date, the Consortium has awarded over £1.5 million to early stage discovery efforts for neurodegenerative diseases. This has included projects that target the immune system to halt nerve cell damage in Alzheimer’s disease and a study targeting TDP-43 aggregation in frontotemporal dementia and amyotrophic lateral sclerosis (ALS). Find further information about the consortium online at



A Template for Clinical Trial Agreements

In March 2016, the Alliance for Clinical Research Excellence and Safety (ACRES) endorsed a standard clinical trial agreement (CTA) template created by Model Agreements and Guidelines International (MAGI) in an effort to break one of the primary bottlenecks for research study startups: the contract negotiation process. In 2004, MAGI started a collaborative effort to create a CTA template that would be widely accepted. Given the diversity of sponsors, sites, and contract research organizations (CROs) in the industry, this turned out to be a significant challenge.

“Real-estate lawyers can negotiate US$30-million transactions in three hours,” said Norman Goldfarb, MAGI Chairman. “We spend three months negotiating $30,000 transactions. There is now a general consensus that the time for a standard CTA template has arrived. Other model CTA initiatives have recently emerged, which we welcome as part of the process of reaching an industry-wide consensus. We can agree to save lives.”

MAGI joins the growing list of nearly 200 organizations and individuals that are teaming up with ACRES and each other worldwide on diverse collaborations to improve the safety, quality, transparency, and cost-effectiveness of clinical research and thus accelerate medicine development. These collaborations increase efficiency, promote standardization, and facilitate the start-up process for clinical trials. The contracting process is challenging for all parties involved, so a standard template provides a significant advance over previous approaches. In addition to creating its 11-page CTA template, MAGI has educated industry professionals about CTAs and certified clinical research contract professionals (CRCP).

“ACRES is all about like-minded, systems-focused organizations and people working together to leverage the good work being done across the clinical research landscape,” said ACRES CEO and cofounder, Greg Koski. “Our collaboration with MAGI is a good example.” He continued that valuable work done by that group created a tool that will benefit everyone. “This is critical because every day of delay is a very costly impediment to the development and availability of new medicines.”

ACRES is a nonprofit, multiple-sector alliance working in the public interest. It brings together diverse stakeholders across clinical research, harnesses their expertise, and adapts lessons from other industries such as transportation, communications, and information technology. For more information, contact Mary Tobin, special advisor to the president and CEO at [email protected].

MAGI streamlines clinical research by standardizing best practices for clinical operations, business, and regulatory compliance. Membership is free, and members get free access to the CTA Template along with more than 150 other forms, checklists, and other standards. For more information, contact Norman Goldfarb, chairman, at [email protected].

T-Cell Therapy Safety and Cost Concerns

T-cell therapy trials have produced exciting results, and such treatments have been hailed as the next big advancement in personalized immunotherapy. After one such trial, researchers at an oncology research institution in Washington reported that six out of seven patients experienced complete cancer remission. But research and consulting firm GlobalData warns in a recent report that questions linger about the marketability of this product class.

Analyst Cai Xuan says that the cost of T-cell therapy is currently estimated at $300,000 per patient, with some experts suggesting that cost could top $500,000 per patient. Thus T-cell therapies must show true curative ability to justify their high prices compared with existing treatment options such as stem cell transplantation, which can cost $100,000–$200,000. So more clinical trials must be conducted. To date, just a few have gone ahead with a limited number of patients because of the high cost as well as the long and difficult manufacturing processes that contribute to that. As discussed in BPI’s cell therapy supplement series (most recently the April 2016 installment), the associated scalability problem cannot be solved easily.

Although cost and scalability are significant issues, Xuan says, perhaps the most difficult barrier T-cell therapy needs to overcome is a poor safety profile. Even in the limited data released so far, fatal cases of tumor lysis syndrome, cytokine release syndrome, and other organ-specific toxicities have been reported. “The aggressive nature of T-cell therapy’s side effects makes it highly unlikely to replace current frontline therapy options,” he says. “A lack of long-term follow-up data presents the danger of additional long-term toxicities being revealed in the future. Data suggesting impressive remission rates of up to 90% in treated patients are preliminary, and it is still too early to tell if these remissions will turn into cures. T-cell therapy is undoubtedly a significant step forward for immunotherapy, but whether it will reach the status of a breakthrough cure remains to be seen.”

Drug Delivery: A Needle-Free Future?

In October 2015, Signals and Systems (SNS) Research released a report on the needle-free drug delivery market. Such delivery methods promise to administer drugs more efficiently and less painfully, with improved patient compliance, than hypodermic needle injections. Needles are still the primary method for delivering large-molecule drugs that if taken orally would break down in the gastrointestinal tract. Despite their common use, however, needles have several drawbacks: pain, needle-stick injuries, patient noncompliance, and needle phobia. Syringes also can be a transmit disease, particularly when they are reused or used incorrectly.

To address those shortcomings, a number of other options have emerged. Among the potential alternative delivery formats are needle-free injections, transdermal patches, microneedles, nasal sprays, and inhalers. Researchers are also looking for ways to allow large molecules to be taken orally. For example, Novartis is currently evaluating a “smart pill” developed by Rani Therapeutics for selected proprietary biologics.

Despite challenges relating to manufacturing, formulation complexities and regulation, SNS Research estimates that needle-free drug delivery will grow to a $5 billion market by the end of 2020. The Needle-Free Drug Delivery Market: 2015–2030 — Opportunities, Challenges, Strategies, and Forecasts report presents an in-depth assessment of this business, covering delivery technologies, key trends, market drivers, challenges, application areas, the regulatory landscape and value chain, leading products, opportunities, and a future roadmap, along with company profiles and strategies. The report also forecasts market size for needle-free drug delivery from 2015 through to 2030, segmented into five delivery platforms, five application areas, five regions, and 25 leading countries. Finally, an Excel datasheet suite provides quantitative data from all numeric forecasts presented in the report.

In the fast-growing biosimilars market, especially, biopharmaceutical companies are increasingly keen to differentiate their products with needle-free technologies. SNS Research expects needle-free injections to gain an estimated market share of 33% by 2020.

Osteoarthritis Treatments on the Horizon

The osteoarthritis patient community can expect novel treatments to arrive over the coming decade to disrupt a market currently dominated by generic pain-relieving treatments, according to research and consulting firm GlobalData. Disease-modifying drugs in late-stage development include Invossa cell mediated gene therapy from TissueGene and Merck Serono’s sprifermin (recombinant human fibroblast growth factor 18), which should launch in the United States in 2020 and 2021, respectively. Both drugs have shown evidence of slowing disease progression, and Invossa also has been found to reduce osteoarthritis pain in clinical trials.

Analyst Lu Chen explains: “Without disease-modifying modalities that slow or reverse the disease progression, many osteoarthritis patients eventually require joint-replacement surgeries and may become disabled. Thus, the need for disease-modifying drugs is immense, particularly considering that the condition is a leading cause of disability in developed countries. Despite this need, osteoarthritis can appear to be static for a long time. Mild cases are largely managed by inexpensive generic drugs. Therapies such as Invossa and sprifermin may experience slow adoption and be limited to use in more severe cases initially.”

He says that both therapies could drastically change the osteoarthritis disease treatment paradigm and market, however. The gene therapy probably will cost more than the recombinant protein, but the former does offer an added benefit of lowering pain as well as slowing joint deterioration. It could achieve US sales of over $560 million by 2024 — compared with about $310 million for sprifermin.

Assuming that those disease-modifying drugs can overcome reimbursement barriers and fully establish cost-effectiveness, GlobalData anticipates broad market acceptance of them over the long term.

Reuters Ranks Top 25 Government Innovators

In March 2016, Thomson Reuters Reuters released its Top 25 Global Innovators ranking of government research institutions. Government organizations pursue “pure research” that private companies often cannot justify or afford. Resulting discoveries can launch entire industries. For example, publicly funded organizations split the atom, invented the Internet, and led space exploration.

To compile the ranking, the intellectual property and science division of Reuters considered more than 500 worldwide government-funded institutions that published the most journal articles and filed the most patents. The United States dominates the list among countries, with its army and navy the only military branches listed. Find more information online at

Here’s the list, from #1 to #25: the Alternative Energies and Atomic Energy Commission (France); the Fraunhofer Society (Germany); the Japan Science and Technology Agency (Japan); the US Department of Health and Human Services; the National Center for Scientific Research (France); the Korea Institute of Science and Technology (South Korea); the National Institute of Advanced Industrial Science and Technology (Japan); the US Department of Energy; the Agency for Science, Technology and Research (Singapore); the French Institute of Health & Medical Research; the Helmholtz Association (Germany); the US Department of Veterans Affairs; RIKEN (Japan); the National Research Council of Canada; the Max Planck Society (Germany); the Chinese Academy of Sciences; the Pasteur Institute International Network (France); the National Institute for Materials Science (Japan); the United States Navy; the Commonwealth Scientific and Industrial Research Organisation (Australia); the Spanish National Research Council (Spain); the Academica Sinica (Taiwan); the United States Army; the National Aeronautics & Space Administration (USA); and the Russian Academy of Sciences.

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