Spotlight

Jupiter images (www.graphics.com) REPRINT WITH PERMISSION ONLY

Infectious Agents: A Global Effort

Worldwide Commitment to Fight Antimicrobial Resistance: Medical, business, and government officials from around the world gathered in Amsterdam for the ECCMID 2016 Conference in April 2016. Hosted by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the meeting reinforced its attendees’ commitment to fight antimicrobial resistance in a concerted effort.

During an interactive session hosted by ESCMID and the Netherlands Society of Medical Microbiology (NVMM), researchers and representatives of the Dutch healthcare administration recommended introducing antibiotic stewardship programs, higher funding of research, and more international collaboration into antimicrobial therapies. They also recommend preventing the spread of infections through better surveillance, vaccination, and public education. Medical professionals need to set clear and binding goals and to continue sharing best practices and strategies that increase public awareness. The so-called “one-health approach” requires joint efforts of medical microbiologists, infectious disease specialists, veterinarians, environmental scientists, public health and government officials, and the public in the fight against antimicrobial resistance.

“Working together, in a spirit of cooperation and with a clear commitment to combat the increase of antimicrobial resistance, we will leave future generations in a healthier, stronger, and more closely connected healthcare approach” said Jan Kluytmans, president of NVMM.

Tackling Superbugs Will Take Money and Teamwork: Nearly 80 pharmaceutical companies expressed their commitment to combatting superbugs by at the World Economic Forum in January 2016. But a recent report from GlobalData points to increased international collaboration and further financial incentives as necessary in the fight against multidrug-resistant microbes. Analyst Mirco Junker says the current economic framework has stifled innovative research and development (R&D) and has led to major drug companies retreating from developing novel antimicrobials.

Junker believes that can be countered through different approaches, such as uptake-independent payments or prolonged protection from generic market erosion for drug innovators. Development of vaccines against infectious diseases that are currently treated with antimicrobials could be encouraged by guaranteeing reimbursements once those vaccines qualify under predetermined conditions. GlobalData believes that improving the funding of international collaborations between for-profit and nonprofit organizations could provide an incentive to the industry without directly paying companies for their R&D.

“Ambitious collaborations between governments, international organizations, companies, and charitable foundations are certainly possible,” Junker explains, “as exemplified by the remarkable success of the vaccine MenAfriVac, which nearly eliminated the prevalence of invasive serogroup A meningococcal disease in 26 sub-Saharan countries. But these partnerships are a delicate balancing act. They must be forged carefully to minimize economic risk for drug developers while also presenting incentives. They also should not completely shift the inherent risk of novel antibiotic R&D from the pharmaceutical industry to academia or nonprofits.”

The analyst concludes that if the mounting threat of antimicrobial resistance is to be effectively controlled, a combination of scientific, regulatory, and economic reforms on the international level must be leveraged.

Viral Infections Market Forecast: Business intelligence provider GBI Research predicts the global viral infections market to grow from US$74 billion in 2014 to $117.6 billion by 2021, with a compound annual growth rate (CAGR) of 6.8%. The company’s latest report, Global Viral Infections Market to 2021: Promising New Competitors and Expanding Treatment Population to Offset Increased Uptake of Generics, states that global initiatives to improve treatment access for people living with chronic debilitating viral infections are key drivers of that growth. Another factor is rising therapy costs because of expensive recently approved and late-stage candidate antiviral agents.

GBI analyst Fiona Chisholm says that 1,848 products are in development to treat viral infections. Among these products, most (419) will target human immunodeficiency virus (HIV), followed by treatments for influenza (333), hepatitis C (222), and hepatitis B (150). The report projects development of generic/biosimilar drugs to increase over the forecast period, especially in major markets (Europe, the United States, and Japan).

Chisholm expects availability of such drugs to increase with a series of recent and upcoming patent expirations for key marketed products, particularly for HIV. “Because of enhanced cost-consciousness,” she says, “clinicians will increasingly favor generics over premium products to reduce treatment cost.”

A Biosimilars Education Initiative

The Biosimilars Forum — a nonprofit organization solely dedicated to expanding patient access to biosimilars in the United States — announced in February the launch of a new education initiative: Partnership for Biosimilars Education and Access. This will focus on raising awareness and encouraging access to biosimilars in the United States. In support of the initiative launch, the Forum released two educational guides (free to download at www.biosimilarsforum.org/resources) with detailed background information, insights, frequently asked questions, and resources.

“Some of the most difficult diseases that afflict people in the United States are best treated with biological medicines,” said Juliana Reed, forum president. The initiative, she explains, is intended to help expand patient access to treatments for indications such as cancer, anemia, multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel diseases.

The US Food and Drug Administration (FDA) approved its first biosimilar in 2015, and more than 50 biosimilars now are in development for the US market. A biosimilar is approved when it is shown to be highly similar to an FDA-approved biological medicine (reference product) with no clinically meaningful differences in safety and effectiveness. Detailed analytical and biological assays support nonclinical, pharmacokinetic/pharmacodynamic (PK/PD) studies, and clinical trials in determining biosimilarity. Learn more at www.biosimilarsforum.org or join the conversation with @USBiosimilars on Twitter.

miranda Knox (www.freeimages.com)

Neurological Markets: The Next Five Years

Parkinson’s Disease Market Could Hit $3.2 billion: Although the Parkinson’s disease market is set to expand from $2.1 billion in 2014 to $3.2 billion by 2021, GBI Research says that a cure will not be available for the foreseeable future. In a report titled, Parkinson’s Disease Therapeutics in Major Developed Markets to 2021, analysts state that this market will grow despite the patent expiries of several key product: Azilect (rasagiline tablets), Neupro (rotigotine transdermal), and Stalevo (carbidopa, levodopa, and entacapone).

Analyst Parnjeet Bains says that four new levodopa formulations are expected to enter the market by 2021, each designed to improve off-episodes in advanced Parkinson’s disease patients by providing continuous drug administration. The focus is on offering easier methods of administration and continuous symptomatic relief.

However, unmet needs remain, and a cure is yet to be found. As with Alzheimer’s disease, no viable therapeutic target to halt or slow disease progression is currently possible because underlying disease mechanisms are not fully understood. To combat the vast array of unmet needs in Parkinson’s disease treatments, developers are concentrating on disease modification rather than mere symptom relief.

“The current pipeline is very active, consisting of 365 products and a diverse range of molecular targets,” Bains says. “A wide range of innovative approaches includes gene therapies and neuroprotective and neuroregenerative agents, suggesting that more effective drugs may be on the horizon.”

Alzheimer’s Disease Market Will More Than Double: In another recent report, Alzheimer’s Disease Therapeutics Market to 2021: Aging Population and Improved Disease Understanding Increase Demand for Disease Modifying Agents, GBI Research predicts impressive growth from just under $5 billion in 2014 to an estimated $10.4 billion in 2021 across North America, Europe, and Japan. Senior analyst Yasser Mushtaq says Alzheimer’s disease is significantly more common in older populations, with incidence rates increasing rapidly after age 65. People are living longer across the globe, leading to more cases of the disease, which poses a growing public health crisis and serious burden for patients and care-takers alike.

Most new drugs will supplement current market leaders by offering patients and physicians more therapeutic options. Promising examples include verubecestat, aducanumab, and azeliragon, all of which have demonstrated clinical benefit and will be approved during the forecast period. Because the underlying disease pathology remains uncertain, thorough research toward understanding it and developing new therapeutics is ongoing. Mushtaq says that although disease prevalence will be the strongest driver of market growth, innovation in the pipeline is also a factor. Drugs in early stages of development contain many first-in-class molecules with novel molecular targets.

Hope for Glioblastoma Patients Comes from Peptide Vaccines and Immunotherapies

Glioblastomas are fast-growing tumors that arise from supportive tissue in the brain. GlobalData senior analyst Dan Roberts says that after Celldex Therapeutics terminated a phase 3 trial assessing its Rintega peptidebased vaccine therapy in March 2016, patients with newly diagnosed glioblastoma must look to other upcoming options. Celldex said that trial was terminated because “Rintega has performed consistently with prior phase 2 studies, but the control arm has significantly outperformed expectations.” Roberts explains that was “not unexpected, as patients who were enrolled in this trial underwent total resection and had no evidence of a progressive disease.” Such patients typically have higher survival rates than the general glioblastoma population.

GlobalData analyst Maxime Bourgognon adds that glioblastoma patients can be optimistic because immunotherapy agents hold great promise for those with high unmet needs and extremely poor prognoses. Some late-stage vaccines in development are expected to improve patient survival, including ImmunoCellular Therapeutics’ ICT-107 autologous cell therapy and Bristol-Myers Squibb’s Opdivo (nivolumab).

“Combining peptide vaccines with active immunooncology products is scientifically and commercially promising,” Roberts concludes. “These combinations will be able to differentiate themselves in an increasingly crowded glioblastoma market.”

www .photos.com

Russia Needs More Drug Manufacturing

The CPhI Russia @ IPhEB conference organized by UBM EMEA, returned to Moscow, Russia, at the end of March 2016. Business opportunities in the country remain diverse, including opportunities for access to the Commonwealth of Independent States (CIS) and Central East European (CEE) regions.

Russia’s 2020 plan provides direct investment by the government of nearly $5 billion in funding with the goal of increasing research and development capabilities and domestic finished-dose pharmaceutical manufacturing.

The country has attracted a strong base of international pharma companies — 76% of its total drug sales come from imported drugs — with many more foreign manufacturers now wanting to capitalize. Russian demand for international pharmaceutical ingredients as well as manufacturing and packaging equipment is increasing as domestic companies seek to upgrade existing facilities to good manufacturing practice (GMP) standards. CPhI Russia acts as a central hub for buyers and sellers within the region.

Growth in the domestic market has enabled CPhI Russia @ IPhEB to expand every year. Exhibitors at the 2016 meeting included InnoPack, Pharmasyntez, Indukern, Protek-SVM, Merck, Serdix, Kelun Kazfarm, and Sotex. This conference provided key insights into market access tactics, including how to evaluate the medical importance of a disease and the therapeutic and economic viability of product candidates. Other sessions covered pilot projects, requirements for accreditation, and comparisons of food supplements and medicines.

UBM EMEA’s Erick Heemsterk says, “Russia is a complex market but one ripe with future potential, and the content and market analysis at this event helps both domestic and international companies evaluate the opportunities.”

Comparing New and Established Markets

GlobalData expects the UK pharmaceutical market to grow from $28.8 billion in 2015 to ~$43 billion in 2020, driven primarily by a robust life-sciences industry. Meanwhile, the market in Indonesia more than doubled from just under $3 billion in 2008 to ~$7 billion in 2015 and is anticipated to increase further to $12.6 billion by 2020 primarily because of the government economic and healthcare initiatives. Both countries and more are detailed in a report titled, CountryFocus: Healthcare, Regulatory, and Reimbursement Landscape.

The United Kingdom’s life sciences sector consists of just under 5,000 companies that develop, produce, and market products and services in the pharmaceutical, medical device, and biotechnology markets. They employed more than 68,000 Britons, including 23,000 scientists and doctors.

GlobalData senior analyst Adam Dion says that is one of the most dynamic industries in the country and a major contributor to the UK economy: “the sixth largest contributor to the balance of trade, contributing $46.9 billion (£32.4 billion) to the economy in 2014, according to the Association of the British Pharmaceutical Industry.” GlobalData’s report also states that the UK’s universal healthcare coverage and easy access to healthcare services, along with increasing rates of disease, have provided momentum for market growth. Healthcare expenditures account for 8.6% of the country’s gross domestic product (GDP) in 2012.

Indonesia’s pharmaceutical sector will be boosted by establishment of its own universal healthcare scheme, known as the Jaminan Kesehatan Nasional. It was launched in January 2014 with the intention of providing health insurance to 250 million Indonesian citizens by 2019. That would make it the world’s largest social health insurance program.

Dion says that growth in Indonesia’s drug sector will also follow from new economic policy packages, a high prevalence of infectious diseases, widespread generic drug supply, increasing affordability of healthcare products, and a large over-the-counter medicines market. “As a consequence of high and consistent economic growth and burgeoning job opportunities, purchasing power has risen, and demand for high-quality healthcare services has increased thanks to greater affordability and improved general health awareness. This will positively affect the growth of the Indonesian pharmaceutical market.”

Despite those overall positive trends, a number of factors limit the expansion of Indonesia’s own healthcare industry. They include a 2010 import tax, widespread counterfeit medicines, periodic price cuts, and limited access to healthcare facilities for the rural Indonesian population. “Indonesia’s pharmaceutical production plants are concentrated around Jakarta and Java, resulting in wide geographical discrepancies,” Dion explains. “In remote areas, many health centers and pharmacies are facing drug supply shortages because of insufficient production by manufacturers and a weak distribution system. Furthermore, the high cost of branded medicines combined with a lack of public reimbursement for expensive and novel drug therapies limits access to efficient medicines. However, this offers a significant opportunity to generic players.”

Drug Life-Cycle Management Strategies

Efforts to extend the life cycle of pharmaceutical products frequently involve improvements in product design, formulation, route of administration, and treatment indications. Drug sponsors sometimes negotiate agreements with their competitors (e.g., generic and biosimilar manufacturers) as part of life-cycle management. Recent changes in patent, regulatory, and antitrust laws have introduced greater complexity and higher risk into such strategies.

In October 2015, lawyers with national law firm BakerHostetler hosted a panel discussion and seminar on this topic. They discussed patent-based exclusivity, US Food and Drug Administration (FDA) exclusivity, antitrust considerations, and generics approval litigation. Participating BakerHostetler lawyers included life sciences intellectual property partner Maurice Valla, pharmaceutical industry partner Lee Rosebush, antitrust partner Carl Hittinger, and life sciences regulatory/litigation partner Lance Shea.

Valla discussed patent law — specifically, early stage drug development, candidate identification, clinical development, approaching approval, launch, and follow-on indications as well as active pharmaceutical ingredient characteristics and new formulations, along with other protection strategies. A significant change in recent patent law makes isolated sequences of DNA no longer patentable unless they are markedly different from naturally occurring forms.

Rosebush pointed out that certain regulatory exclusivities can supplement patent protection: new chemical entity (NCE), new clinical investigation (NCI), orphan drug, pediatric, and biologics license application (BLA) exclusivities. He said, “From the application perspective, we’re really looking at two potential exclusivity issues for brand-name applications: the NCE for five years and the NCI for three years.”

Each exclusivity has specific criteria that must be met by applicants/sponsors, and each excludes certain defined competitive activities. Such requirements are meant to encourage development of new, safe, and effective treatments. Using them can provide a return on investment, and Rosebush warns that not using them can increase competition and lead to expensive litigations.

Hittinger discussed three important cases under antitrust laws. He said that the Federal Trade Commission (FTC) can act against “unfair methods of competition” and therefore has broader powers than the Department of Justice or litigants under the Sherman Act. Hittinger suggested that companies consider asking for a formal FTC review before engaging in questionable conduct involving competitors or when entering into settlements.

“Patent law and antitrust law are in constant tension,” he said. “That tension exists because a patent is by definition a monopoly. Exclusivity and monopoly are things that the antitrust laws were aimed at preventing or at least controlling, and therefore the ebb and flow of that over the past 100 years in the courts and in Congress has been one of increased tension.”

Shea focused on litigation arising near the end of drug-marketing exclusivity periods. Similar to Hittinger, he proposed having early communication with regulators about generic/biosimilar approval issues such as bioequivalence. Companies also need a deep knowledge of and good data for the drug of interest. He emphasized considering exclusivity issues early in a drug product’s life cycle. Because bioequivalence must be demonstrated for generic approval, decisions made about a potential drug’s attributes and modes of action will affect the evidence needed for ANDA approval. Biosimilars have their own special considerations.

You can find a summary of the seminar — Pharmaceutical Life Cycle Management: Navigating the New IP, FDA and Antitrust Terrain — online at http://bakerlaw.com/files/uploads/News/Articles/LITIGATION/FDA/Brief-Pharmaceutical-Life-Cycle-Management.pdf.