Category Archives: Pharmaceutical

Method to predict drug stability could lead to more effective medicines

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Researchers have developed a new method to predict the physical stability of drug candidates, which could help with the development of new and more effective medicines for patients.

Researchers from the UK and Denmark have developed a new method to predict the physical stability of drug candidates, which could help with the development of new and more effective medicines for patients. The technology is being developed for use in the pharmaceutical industry in order to make medicines that are more easily released into the body.

The researcher’s method solves an old problem: how to predict when and how a solid will crystallise. Using optical and mechanical measuring techniques, they found that localised movement of molecules within a solid is ultimately responsible for crystallisation.

Solids behave differently depending on whether their molecular structure is ordered (crystal) or disordered (glass). Chemically, the crystal and glass forms of a solid are exactly the same, but they have different properties.

Molecules in the glass form are more readily absorbed by the body because they can dissolve more easily

One of the desirable properties of glasses is that they are more soluble in water, which is especially useful for medical applications. To be effective, medicines need to be water-soluble, so that they can be dissolved within the body and reach their target via the bloodstream.

“Most of the medicines in use today are in the crystal form, which means that they need extra energy to dissolve in the body before they enter the bloodstream,” said study co-author Professor Axel Zeitler from Cambridge’s Department of Chemical Engineering & Biotechnology. “Molecules in the glass form are more readily absorbed by the body because they can dissolve more easily, and many glasses that can cure disease have been discovered in the past 20 years, but they’re not being made into medicines because they’re not stable enough.”

After a certain time, all glasses will undergo spontaneous crystallisation, at which point the molecules will not only lose their disordered structure, but they will also lose the properties that made them effective in the first place. A long-standing problem for scientists has been how to predict when crystallisation will occur, which, if solved, would enable the widespread practical application of glasses.

“This is a very old problem,” said Prof Zeitler. “And for pharmaceutical companies, it’s often too big of a risk. If they develop a drug based on the glass form of a molecule and it crystallises, they will not only have lost a potentially effective medicine, but they would have to do a massive recall.”

In order to determine when and how solids will crystallise, most researchers had focused on the glass transition temperature, which is the temperature above which molecules can move in the solid more freely and can be measured easily. Using a technique called dynamic mechanical analysis as well as terahertz spectroscopy, Prof Zeitler and his colleagues showed that instead of the glass transition temperature, the molecular motions occurring until a lower temperature threshold, are responsible for crystallisation.

These motions are constrained by localised forces in the molecular environment and, in contrast to the relatively large motions that happen above the glass transition temperature, the molecular motions above the lower temperature threshold are much subtler. While the localised movement is tricky to measure, it is a key part of the crystallisation process.

Given the advance in measurement techniques developed by the Cambridge and Copenhagen teams, drug molecules that were previously discarded at the pre-clinical stage can now be tested to determine whether they can be brought to the market in a stable glass form that overcomes the solubility limitations of the crystal form.

“If we use our technique to screen molecules that were previously discarded, and we find that the temperature associated with the onset of the localised motion is sufficiently high, we would have high confidence that the material will not crystallise the following manufacture,” said Prof Zeitler. “We could use the calibration curve that we describe in the second paper to predict the length of time it will take the material to crystallise.”


Launch of first breast cancer biosimilar in the UK

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MSD has announced the launch of Ontruzant®, (trastuzumab), a biosimilar referencing Herceptin® (trastuzumab/TRZ), for the treatment of early breast cancer, metastatic breast cancer and metastatic gastric cancer.

This was the first trastuzumab biosimilar to receive regulatory approval in Europe and is the first to launch in the UK.

Biosimilar trastuzumab represents the first product approved in the UK under a global biosimilars development and commercialisation agreement between MSD and Samsung Bioepis Co Ltd.

The European Medicines Agency (EMA) requires biosimilars to show they are highly similar to the reference medicine in terms of structure, biological activity and efficacy, safety and immunogenicity profile. Ontruzant (trastuzumab biosimilar (SB3)) is a monoclonal antibody and has been shown to have similar safety and efficacy as its reference product Herceptin (TRZ) in early breast cancer, with breast pathologic complete response rates (bpCR) being 51.7% and 42.0% with SB3 and TRZ respectively. The adjusted ratio of bpCR was 1.259 (95%CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within and the upper limit outside the equivalence margin. The overall response rates were 96.3% and 91.2% with SB3 and TRZ.

Dr Mark Verrill, Head of the Department of Medical Oncology at the Newcastle upon Tyne Hospitals NHS Foundation Trust, and the deputy lead clinician for breast cancer in the North of England Cancer Network said, “This is good news for so many cancer patients and the NHS. The launch of biosimilar trastuzumab provides a high-quality treatment alternative for patients, while offering significant potential savings for the NHS. The biggest category of medicines in oncology is monoclonal antibodies and the introduction of biosimilars such as trastuzumab could provide a substantial cost saving.”

Denise Blake, Senior Lead Clinical Pharmacist at Newcastle Hospitals, explains, “The introduction of biosimilar trastuzumab provides an opportunity for the NHS to realise substantial financial savings without compromising patient care. Close collaboration between oncologists, pharmacists and nursing staff is required to ensure a seamless introduction into routine clinical practice.”

“As a company committed to inventing new treatment options for both common and neglected types of cancer, MSD is also pleased to be offering the NHS a biosimilar medicine in an established area of care. Biosimilar trastuzumab marks a significant milestone for both MSD and the oncology community, providing the UK’s first biosimilar trastuzumab, based on our collaboration with Samsung Bioepis,”explains Louise Houson, UK Managing Director, MSD.

Regulatory approval was based on a Phase III study that compared SB3 with reference TRZ in patients with human epidermal growth factor receptor HER-2 positive early breast cancer in the neoadjuvant setting.

The study showed the total pathologic complete response rates were 45.8% and 35.8% and the overall response rates were 96.3% and 91.2% with SB3 and TRZ, respectively. Eight hundred patients were included in the per-protocol set (SB3, n = 402; TRZ, n = 398). The bpCR rates were 51.7% and 42.0% with SB3 and TRZ, respectively. The adjusted ratio of bpCR was 1.259 (95%CI, 1.085 to 1.460), which was within the predefined equivalence margins. The adjusted difference was 10.70% (95% CI, 4.13% to 17.26%), with the lower limit contained within pre-specified equivalence margins and the upper limit of the confidence interval slightly exceeding the pre-specified equivalence margins (-13%, 13%).

Overall, 96.6% and 95.2% of patients experienced one or more adverse event, 10.5% and 10.7% had a serious adverse event, and 0.7% and 0.0% had antidrug antibodies (up to cycle 9) with SB3 and TRZ, respectively.


Summit Therapeutics to expand clinical trials after healthy interim results

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Summit Therapeutics will expand enrollment in its phase 2 clinical trials studying the effect of ezutromid treatment on Duchenne muscular dystrophy (DMD), the company said on Wednesday.

The PhaseOut DMD trial is a multi-centre, 48 week open-label clinical trial with 40 enrolled patients between the ages of five and ten who suffer from DMD which will be enhanced by the newly announced parallel running expansion.

David Roblin, chief operating and medical officer of Summit, said: “We are extremely grateful to the patients who participated in our Phase 1 clinical trials and contributed to ezutromid’s clinical advancement, but were not initially eligible to participate in our Phase 2 clinical trial. Accordingly, we are pleased to open this additional group in our Phase 2 and provide these patients with the opportunity to receive ezutromid treatment.”

Patients with DMD will be eligible for the expanded trial regardless of their age or ambulatory status.

DMD is a muscle wasting disease that affects approximately 50,000 men and boys in the developed world and is caused by genetic faults in the gene that codes dystrophin and thus preventing the healthy function of all muscles.

The orally administered small molecule drug is intended to modulate utrophin, a protein functionally and structurally similar to dystrophin, with the aim of slowing or even halting DMD.

Recently announced 24 week interim data from the trials demonstrated that compared to baseline, ezutromid significantly reduced muscle damage and muscle inflammation attributed to the disease.

“We expect the data collected from this additional group of patients will help expand our understanding of ezutromid’s safety and efficacy profile across a broader patient population,” said Roblin.

Ezutromid has been granted Fast Track designation and Rare Pediatric Disease designation by the US Food and Drug Administration (FDA) as well as orphan drug status which allows for additional regulatory support and a period of market exclusivity following approval.


How Cuba Became a Biopharma Juggernaut

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

We hear little about the Cuban biopharmaceutical industry, but it merits attention.

The sophisticated system, which the small island nation developed despite limited resources and access to international markets, holds about 1,200 international patents and sells medicine and equipment to more than 50 countries. The industry is entirely publicly funded and managed, and is a key component of one of the most efficient public health care systems in the world. Its goal is to develop drugs of strategic importance to the health care of all people.

igh-tech industrial development isn’t the first thing that comes to mind for many when thinking of Cuba. The island nation more commonly invokes visions of a stunning place frozen in time: Crumbling colonial buildings sit alongside beautiful beaches, while 1950s American cars line city streets awash in the sun’s afternoon glow. Here, life is embedded in a state-controlled and mostly inefficient economy that’s virtually detached from global technology networks.

But there’s something missing in this outsiders’ view of the country, as it can’t account for the enormous successes of Cuba’s biopharmaceutical[1] industry and health care systems. In light of ongoing debates in the U.S. and other nations about the role of government in ensuring people have the health care coverage they need, Cuba’s experience could prove instructive.

There is growing evidence of the Cuban biopharma industry’s success. Local production covers more than 60% of finished pharmaceutical products used in the country, and the industry’s trade balance has remained consistently positive for most of the period 1995-2015. Cuba’s biopharma sector has been able to finance many programs carried out within the nation’s public health system, and it is the main reason behind the affordability of the medical products supplied by the system. In terms of the biotechnology sector specifically, while Cuba’s government does not publish extensive statistics on the matter, industry officials report that the Cuban biotech sector managed to maintain positive, if modest, cash flows at a time when overall cash flows of the industry worldwide had been mostly negative for decades.[2]

While not popularly understood outside the country, Cuba’s biopharma achievements have been recognized by the international scientific community. In 2005, the Laboratory of Synthetic Antigens, a small lab that belongs to the faculty of chemistry of the University of Havana, won the World Intellectual Property Organization (WIPO) Gold Medal Award for developing the world’s first synthetic vaccine (Quimi-Hib) against haemophilus influenza type b (or Hib). More recently, the CIMAvax-EGF vaccine for lung cancer became the first Cuban biopharmaceutical product to earn the U.S. drug regulator’s permission to carry out clinical trials on American soil. The product was developed by the Center for Molecular Immunology, which specializes in antibodies, cancer medicines, and other areas.

Had Cuba been forced to acquire most of its needed medical products at current international prices—rather than develop them on its own—it would not have been able to achieve its  remarkable health advances at a relatively low cost. No matter how well intentioned the government might have been with respect to public health, it would not have been able to subsidize an entire country’s essential medicines. Cuba has, of course, followed a different model, prioritizing domestic innovation and production.

It’s true that high levels of innovation make the Cuban biopharma industry an exception within the country’s overall industrial sector, which lags behind in many areas. However, it has not been an exception in terms of the environment in which it has grown. The architecture of Cuba’s health care system, and the nation’s public investment in free education, research, and innovation, have all been critical factors in the biopharmaceutical industry’s success story, making it a testament to the complexities of economic development, as well as of the role of history and institutions in shaping structural change.

Meeting the Needs of Universal Public Healthcare

Essential to the success of Cuba’s biopharmaceutical industry is the country’s public health care system, which was designed to meet the medical needs of the entire population. The organizing principle of the biopharma industry—as a result both of economic necessity and of Cuba’s publicly stated values—has been producing affordable medicines. It is supported by Cuba’s medical philosophy, which prioritizes prevention—the only viable path for a poor country to provide universal healthcare affordably. The public health care system demands that the industry produce low-cost, high-quality products, and supports it in doing so. As a result, Cuba has become a successful exporter of medical products, particularly biopharmaceuticals.

It all began with an emergency. Before the 1959 revolution, the Caribbean island had been home to a number of highly-trained, well-respected physicians. But nearly half of them left for the United States following a disagreement with the revolutionary authorities over institutional changes they were implementing. The government’s new measures included a unified regulatory framework for all levels of the system—which prior to the revolution had been painfully fragmented—along with a 15% price reduction for home-grown medical products and a 20% cut for imports. The changes provoked foreign companies that dominated the Cuban market, which until that moment had been free to set prices for their products without government regulation, as well as the laboratories, retailers and medical personnel linked to them. The clash led to many closures and other actions, creating a supply crisis that resulted in the nationalization of the industry in 1960.

Those events happened within the context of an already widespread public rejection of profit-seeking medical practices, which encouraged the government to intervene in private clinics and hospitals and to change the country’s philosophy of medical education. At that time, medical guilds were among the most powerful associations in the country, and also were among the most wary of the transformations that were taking place, for both political and financial reasons. From 1959 to 1967, a country with six million inhabitants lost 3,000 of its 6,300 physicians (not including new graduates in those years) and found itself with just 22 professors of medicine and a single medical school. They were sorely needed just as the new government-initiated reforms—designed to increase the availability of health services to underserved areas—were taking effect.

Their exodus prompted state investment in medical education—including the creation of a comprehensive primary care system—while priorities in training doctors shifted to focus on preventative medicine. The guilds disbanded in 1966 as a government-based nationwide union was created, and those in favour of deepening the changes were now free to carry out the project. Medical graduates had already been encouraged to serve in rural medical facilities and not engage in private practice. However, even when the government strongly discouraged, and eventually prohibited, opening new private clinics, a number of practices that already existed and complied with the new measures were allowed to continue. Until the public health system absorbed the last non-public clinics in 1970, the Cuban healthcare system, as it did before the revolution, consisted of three types of healthcare services: public provision, mutual clinics and private provision.

During the first half of 20th century, large public hospitals emerged in the country and provided free services, but they were limited to major cities and were chronically underfunded prior to 1959. Mutual clinics were created by mutual societies of Spanish origin and functioned within cooperative framework. In return for a monthly fee, members of these societies received high-quality medical services of high quality. At the same time in the first half of the 20###sup/sup### century, a significant network of private clinics flourished. They also provided high-quality services, but mostly worked on the profit principle, excluding the millions of people who could not afford to pay. The creation of rural services and other reforms were part of the government’s efforts to provide truly universal access to health services, and to encourage a new ethos of cooperation and solidarity within the medical profession.

Some testimonies of those involved as students at that time show that, even if the government deployed a good deal of ideological exhortation and public relations to attract new graduates for rural medical services, these graduates could choose where they wanted to work. Some decided to go to private clinics or to better-remunerated posts, but most decided to serve in remote rural places out of ideological or civic concerns.

These developments need to be seen within the context of the time and the atmosphere of ideological confrontation that served as inspiration for many young people. Many of them decided to put aside better pay and more comfortable working conditions in favour of serving higher ideals. Government efforts could also be interpreted as a huge behavioural intervention aimed at replacing external motivations for practicing medicine related to prestige and salary for more internal motivations related to personal fulfilment from serving a higher purpose.

The system these graduates were joining, and that Cuba was building, involved an open atmosphere of knowledge-sharing and cooperation. In the context of a centralized, nationwide system, the Cuban health care sector is able to save both time and money. To be sure, “centralized” means that methods and services are standardized and centrally designed. However, medical care and education, even if public, was conceived as a decentralized network of community clinics and hospitals equipped to tailor services to the local population’s needs.

In addition, the focus on primary care ensures the system can collect and synthesize community-based information about the population’s health and disease patterns. This data collection is part of a bigger project: Cuba’s comprehensive, integrated national medical record system determines where greatest health risks to society lie, allowing the government to more efficiently allocate resources. This structure can also substantially reduce drug development because it speeds up informed-consent enrollment in clinical trials—the backbone of drug and treatment development. The government intentionally designed the system in this way to further organizational learning and social efficiency.

The Role of Free Education and Early Investment in Science

Another important part of the Cuban biopharma success story is the broader crusade the government has carried out in favour of more education and scientific research. The resulting investments allowed the country to absorb and translate knowledge into innovative, world-class products.

While the Cuban biotech industry started developing in earnest in the early 1980s, its foundation dates back far earlier. Most Cuban biotechnology research centres emerged from already-existing research groups and labs. But with the exception of maintaining key personnel, most new institutions had to be built from scratch after the revolution, with the support of the Cuban state’s intense investment in scientific research since the 1960s.

One of the most important transformations experienced by Cuban academic medicine during the 1960s was the integration of scientific research into the government’s public healthcare strategy. The period prior to the revolution saw the development important medical scientific institutions. But they had developed because of the individual perseverance of their founders rather than consubstantial elements of public healthcare strategy. Some key examples include the Institute of Cancer, created in 1929, and the Institute for Tropical Medicine, created in 1937. Most research institutions, however, disintegrated in 1959 because their founders had political differences with the government; most of them left the country. A very small, select, group of experts stayed. They, together with younger, inexperienced professors sympathetic to the new government, as well as a significant number of foreign experts invited to teach, helped rebuild the scientific landscape in Cuba. They sophisticated it to an extent unknown in country’s history.

The main organization, born in 1965, is the Centro Nacional de Investigaciones Cientificas (CNIC). Many industry leaders in Cuba received their first scientific training at CNIC, originally a non-profit staffed by a small group of recently-minted physicians. These doctors had answered the government’s call to dedicate themselves to biomedical research. CNIC also employed chemists and engineers of different specialties. As remuneration was far from attractive and the training very demanding, only those really interested in science, and with the talent to afford the task, applied to be graduate students or researchers at CNIC. That first year only 13 students were selected to take the training. There is a testimony of one scientist who, prior to entering the training, turned down a salary of 600 Cuban pesos as assistant professor in favour of a residency in microbiology, where the salary was only 200 pesos. For him, it was about devotion to science.

The main goal of CNIC in its first years was to increase young medical graduates’ knowledge of the sciences and mathematics, and to initiate them into research tasks. It was a postgraduate school designed to produce high-level scientists. To that end, CNIC organized a series of courses and practices taught by Cuban and foreign professors. After taking these courses, several young researchers won graduate scholarships to study in Western and Eastern European countries, which exposed them to the leading research in their fields. Institutions such as the Pasteur Institute, Harvard University, Heidelberg University and Zurich University, to name just a few, hosted Cuban researchers during or after their formative years in CNIC. The fact that the beginnings of the Cuban biotech industry were developing at the same time as the beginnings of genetic engineering worldwide helped put Cuban institutions at the leading edge of the technological frontier.

As it developed, this multi-disciplinary institution became a hub for chemical and biological experimental research and an incubator for Cuba’s other scientific institutions. For example, as early as 1978, researchers at CNIC´s Microorganism Genetic Department knew about the possibility of recombination and were already working on the genetics of microorganisms and molecular biology. In simple terms, recombination involves constructing brand new genetic material (DNA molecules) by mixing (or combining) genetic material from different organisms. In 1986, U.S.-based biotechnology company Chiron developed the technology to obtain a genetically engineered (or DNA recombinant) hepatitis B vaccine; that same year, the Cuban recombinant vaccine was developed using a cheaper method.

A small but impactful neurophysiology unit created within CNIC in 1966 became Cuba’s Neurosciences Centre in 1990. It’s worth noting that the pioneer of the field in Cuba—and founder and current director general of the Cuban Neuroscience Centre—co-authored of a foundational paper with a renowned American neuroscientist. The Centre made Cuba the world’s first public health system to systematically use the quantitative electroencephalogram (qEEG)—a test that analyses the brain’s electrical activity to identify defects or problems.

Since the 1990s, CNIC adopted the form and function of a typical company by focusing on developing products and integrating a trading arm into its structure. But its origin as a focal point of the industry reflected the culture of cooperation that distinguishes the Cuban biopharma industry. Even if the core biotech firms within the industry function under what Cuban officials call a “closed cycle” system (a fluid form of vertical integration), formal or informal co-development are the signature of the industry. The complete realization of CNIC’s most innovative products has often been the result of some sort collaboration between at least two companies. This risk-sharing model has also become a very effective way of providing access to international markets, often in the form of carefully conceived partnerships, technology transfers, licensing and co-marketing agreements.

Cuba’s Enduring Scientific Success

Given this early investment, Cuba’s biopharma industry has evolved rapidly over the past four decades. Tracing its development over that period reveals the resourcefulness and commitment of the Cuban government and the island’s scientists. It also reveals the industry’s breakthrough scientific success.

The Scientific Pole, also known as West Havana Biocluster, was officially created in 1992. Its origins date from 1980 when oncologist Richard Lee Clark, who had served as president of the first cancer hospital in the U.S., travelled with a North American delegation to the island. There he met several Cuban government officials, with whom he discussed his groundbreaking research on interferon, considered a “wonder drug” in the battle to cure cancer. Shortly thereafter, Clark hosted two Cuban scientists at his hospital in Houston, Texas, sharing his research and expertise.

At the direction of Clark, Cuban researchers travelled the following year to the Helsinki-based laboratories of Dr. Kari Cantell, who first isolated interferon from human cells in the 1970s. Six Cuban scientists spent a week working with Cantell and his colleagues learning how to reproduce interferon in large quantities. Upon their return home, they set up a special laboratory in a small house in Havana to try to reproduce the Finnish results and produce interferon in Cuba. By the end of that year, 1981, they had succeeded. Eventually, the product proved not to be a wonder drug against cancer, but instead beneficial against dengue fever—an outbreak of which severely affected Cuba in the 1980s.

In the years that followed, the government policies helped implement a number of additional small pilot projects run by new interdisciplinary working groups, such as the Biologic Front in 1981 and the Center for Biological Research in 1982. When the United Nations Industrial Development Organization (UNIDO) decided to create an institution of excellence for the transfer of biotechnology to developing countries, Cuba applied for the vacancy but lost out to India. Determined to move forward, the Cuban Government then decided to create its own organization with its own resources.

By 1986, Cuba inaugurated CIGB (Centro de Ingeniería Genética y Biotecnología), now one of the country’s most outstanding biotechnology companies. Other important institutions followed. Among the most representative is the Immunoassay Center, created in 1987 to producing and commercializing diagnostic systems. The Finlay Institute opened officially in 1991, and the Center for Molecular Immunology in 1994. Many of these institutions have helped Cuba sell millions of dollars’ worth of biopharmaceutical products.

Greater integration with the rest of the world’s markets could increase the country’s already positive pharmaceutical trade balance from $86 million in 2015 to $119 million by 2020, according to estimates from Business Monitor International (BMI) Research. These are, of course, modest results compared with the performances of leading nations. However, they become impressive when you consider the point of departure and the fact that the biotechnology industry worldwide has historically found it very hard to achieve positive cash flow.

Looking at specific drug succeses, Cuba has produced a number of innovative drugs and vaccines as a result of advances in its biotech sector. Alongside the lung cancer and Hib vaccines mentioned earlier in this article, it has also produced policosanol (PPG), a pharmaceutical derived from sugarcane that reduces morbidity and mortality from atherosclerotic cardiovascular disease. CNIC developed the product, which won a World Intellectual Property Organization (WIPO) gold medal in 1996. Another gold medal winner was Heberprot-P, a novel biomedicine developed by the Centre for Genetic Engineering and Biotechnology (CIGB) for treating foot problems in diabetics. It won the WIPO Award for Best Young Inventor and a WIPO gold medal at the International Inventions Fair in 2011.

Often, these drug innovations from Cuba fail to get the recognition they deserve. Cuba’s VA-MENGOC-BC®, for example, was the first world’s commercially available vaccine against serogroup B meningococcus. The product, developed by the vaccine-focused Finlay Institute, was awarded WIPO’s gold medal in 1989. At the time, it attracted attention from the pharmaceutical giant SmithKline Beecham (now part of GalaxoSmithKline)—but not from the media. Many years later, Swiss drug maker Novartis was mistakenly credited with developing the first vaccine of its kind to fight Meningitis B. Cuba had the drug 24 years earlier[3].

The Upsides and Downsides of Government Involvement

There’s no doubt that Cuban biopharma is an exception within the country; Cuba’s overall economy lags behind in both regional and world rankings. Chronic underperformance and lack of dynamism have been recognisable features for decades. Most sectors in Cuba have a long way to go in terms of international competitiveness, particularly after the economic crisis sparked by the collapse of the Soviet Union, Cuba’s main trade partner during the Cold War. After 1991, and more visibly since 2008, the government introduced several reforms aimed at boosting the economy. But deep inadequacies remain unresolved.

Studies of these structural problems dominate the literature on contemporary Cuba and permeate the current conversation on the subject. Most of them, regardless of ideological persuasion, largely look at on the macroeconomic consequences of, and possible solutions for, these shortcomings. And yet, whether coming from a sympathetic or a downright hostile perspective, most commentators admit that Cuba has created an impressive medical workforce that has produced results.

But if international audiences are more or less familiar with the fact that Cuba has managed to achieve successful health outcomes in many basic indicators—relative to averages for similar populations—it is far less understood that a major factor producing these achievements is a sophisticated industry that sells medicine and equipment to countries around the world.

An exception was a 2009 editorial published by the magazine Nature, which said Cuba had “develop[ed] the world’s most established biotechnology industry, which has grown rapidly even though it eschewed the venture-capital funding model that rich countries consider a prerequisite.”

It’s true: Cuban biotech is a 100% government investment. It’s a sector whose development has avoided the financialized model that has shaped the industry worldwide. And yet, well beyond Cuba, a government as acting as investor in high-tech industries is no new thing. Particularly in the biopharmaceutical industry, government investment has played a critical role in most every country. Consider the U.S. government’s National Institutes of Health (NIH) support of the creation of American biotech, or the programs of the German Federal Ministry of Education and Research, among many other examples. There is actually nothing unusual about the Cuban government’s investment and its strong involvement in biotechnology.

The singularity may come with the fact that Cuba is not only a developing country hindered by a robust economic embargo, but also a communist-socialist country with (until very recently) a fully state-controlled economy, of which the 100% state-owned Cuban biotech sector is part. The business of producing medical products was largely underdeveloped in Cuba before the revolutionary government got involved: foreign subsidiaries controlled 50% of the market, importers accounted for a further 20%, and local generic production was accountable for the remaining 30%. In the 1960s, the government acquired private local producers, and foreign producers reduced imports and closed their plants. In the 1970s, in order to minimize the impact of the U.S. embargo, the government began its first investments in pharmaceutical production plants. Initially, drug purchases from both Western and Eastern Europe complemented these efforts. Then came the biotech.

One does not need to admire the Cuban political system to recognize the success of what observers deemed Cuba’s “billion dollar biotech gamble”: a reference to the seemingly unrealistic decision to invest $1 billion in the 1980s and the 1990s to develop the sector. It’s a “gamble” that has turned out to be the most successful Cuban R&D programs, and one that can serve as a model for other nations.

The lion’s share of today’s Cuban biotech industry is concentrated in BioCubaFarma, a state holding created in 2012 with the government’s economic reforms[4]. It is a vast holding that comprises 33 companies that host more than 21,600 workers—hundreds of them highly-skilled professionals deeply integrated within several research-production activities. One of its explicit goals is to double the exports of the Cuban biopharmaceutical industry to reach more than $1 billion per year within five years. That would have totalled $5.076 billion—a huge difference compared to the previous five years, which saw total exports of $2.779 billion. Whether the industry has achieved this goal is hard to say given the lack of data, so a reasonable assessment of BioCubaFarma’s performance will need to wait.

There are factors that would have helped Cuba achieve this goal, and others that could have hindered it. One aspect that would have helped is the re-establishment of diplomatic relations with the U.S., which relieved many potential buyers and investors from some of the pressures associated with the economic sanctions. On the other hand, the industry needs to do more to incentivize its workers. While in the past, even in the middle of the crisis of the 1990s, qualified personnel were willing to work hard despite lesser financial gains, that doesn’t seem to be so much the case now.

An excessive focus on financial rewards has not helped incentivize workers; in fact, it has proven one of the downsides of the new economic measures introduced since 2008. Important wage increases have taken place since 2014 especially in the health sector, benefiting more than 440,000 healthcare workers, who in most cases saw their salaries grow by more than 100%.

These wage increases do not appear to be having their intended effect of retaining a motivated workforce and boosting productivity; in fact, they appear to be negatively impacting the motivational balance of the biotech workforce. They may have over-stimulated the financial awareness of some employees to the point of irritation, and to the detriment of internal motivation. The industry has seen 40% of its workforce quit over the last two years. Not all of those leaving are scientists, but it is still an alarming number.

Even with all the challenges, in 2014 and 2016 $1.293 billion and $1.940 billion has been saved, respectively, by import substitution. Still, the government needs to better understand behaviour in innovative organizations, and which measures will encourage or discourage employee motivation—a key element in the good functioning of those organizations. If the success of the Cuban biotech actually depended on the high remuneration of their employees, this industry would simply not exist as it does today.

Defying Simplistic Analysis

There is no way one can digest Cuba’s biotech story while relying on conventional narratives on economics and economic development. Adhering to traditional frameworks, and failing to engage in an accurate institutional analysis, would make it impossible to understand how a cash-driven, high-tech industry successfully developed in a poor, developing country.

Because the island is in many ways a singular place, observers inevitably find themselves referring to its many particularities as explanations for the sector’s success. Almost all traditional studies contain important reflections related to institutional questions and other issues specific to Cuba. However, most of these discussions tend to underplay the complex relationship among institutions, innovation and economic development. They tend to end on a static, pessimistic note of conclusion. The analysis of, for example, property rights, ownership, competition, regulation, corporate governance, and related issues is coloured by the simplistic and linear, one-size-fits-all tendencies of neoclassical economics.

As cross-country historical evidence suggests, structural change is a highly idiosyncratic process, which usually works in far more complex ways than assumed. Technological conditions in an economy are the result of non-linear interactions among cultural, geographical, historical and socio-political elements, rather than pre-determined assumptions about behaviour. Innovation is, by most accounts, a messy, uncertain process, which often has little to do with the straightforward causalities conventional narratives offer. Too often, liberalization and privatization are presented as inalienable and natural preconditions, and it becomes impossible to engage in analysis outside that framework. If we want to truly understand the formation and evolution of innovative firms and industries, we need to analyse them in their contexts and be open to what may emerge.

And so it happens that what emerges from a nuanced analysis often has a very unfamiliar face for contemporary audiences. When properly examining Cuban industry, for example, we discover powerful stories that challenge the homogenizing nature of most traditional studies of innovation, with their emphasis on property rights and returns to inventors. The Cuban biotech industry undoubtedly represents the most successful case of science and technology policy in that country’s economic history.

It is also a case that illustrates how having a competent and motivated scientific workforce is a determining factor in a country’s ability to upgrade its economic structure. Cuban scientists learned about biotech when few in the world believed in its potential. They grew along with the research, and therefore were in a better position to take the lead in developing unique innovations. It was, and still is, a risky move, but that’s the history of economic development. This finding opens up scope for other sorts of reflections on the Cuban context in particular, and could ultimately help reshape policymakers’ choices regarding future industrial projects.

Of course, the whole issue inscribes itself within the of-the-moment discussion on the legitimacy of the government’s role as science and technology sponsor. The Cuban example in many ways shows us the good sides of public health and the virtues of a well-calibrated government policy. Of course, Cuba’s path does not need to be mandatory for everybody, but it may be valid for many. And learning about it may help us overcome our own biases—as economists and as human beings.


[1] In the Cuban context, the term “biotech” is interchangeable with “biopharma,” and this article uses the terms in this way unless otherwise noted.  Biopharmaceuticals are the products you obtain through the biotechnology process; in other words, biotechnology creates biopharmaceutical products.

More specifically, from a definitional standpoint we understand the biopharmaceutical industry in the way most academics and practitioners (including in the U.S.) usually do, i.e., as a subset of a huge industrial sector devoted to the production of medical products, be they chemically (in the case of pharmaceuticals) or biotechnologically (in the case of biopharmaceuticals) produced. In Cuba this industry is mostly identified with the biotechnology because it is this subset the one that has become commercially relevant, which in turn has contributed to push forward the pharmaceutical side of the industry (mostly in form of generics for the domestic market). Again, this piece uses the terms “biotech” and “biopharma” interchangeably to refer to the Cuban biotech; it makes particular sense for the Cuban case and doing so is compatible with mainstream definitions.

[2] This reference to negative cash flow points to the aggregate results of the biotechnology firms, whose historical performance has been on the whole disappointing in terms of profitability and cash flow. This assertion does not include the traditional pharmaceutical companies, but it has implications for the future of many pharmaceutical firms that are more and more dependent on their biotech subsidiaries, or on their alliances with biotech firms—to the point that they can no longer be definitionally separated.

[3] In 2013 Novartis, received approval from the European Union to market its Bexsero against Meningitis B. The U.S. Food and Drug Administration (FDA) granted accelerated approval in January 2015. The international press has erroneously presented this vaccine as the first of its kind that has successfully fought the condition. Even if the new vaccine is said to be designed for different strains, it is not the first commercially available version—nor, as often repeated by the press, was it the first to be successfully employed in a nationwide meningitis B programme for children. Cuba’s VA-MENGOC-BC®, which also has the potential to fight several strains, has been used in Cuba and other countries for more than two decades with impressive results.

[4] The entity derived from the merger of all institutions of the Scientific Pole in western Havana, the biotechnological side of the industry, and all companies within the Quimefa Group, which represented the traditional Cuban pharmaceutical industry. Quimefa was a state holding created in 2001 devoted to producing small molecules (chemically-based drugs), mostly generics, to substitute for imports.

[1] In the Cuban context, the term “biotech” is interchangeable with “biopharma,” and this article uses the terms in this way unless otherwise noted.  Biopharmaceuticals are the products you obtain through the biotechnology process; in other words, biotechnology creates biopharmaceutical products.

More specifically, from a definitional standpoint we understand the biopharmaceutical industry in the way most academics and practitioners (including in the U.S.) usually do, i.e., as a subset of a huge industrial sector devoted to the production of medical products, be they chemically (in the case of pharmaceuticals) or biotechnologically (in the case of biopharmaceuticals) produced. In Cuba this industry is mostly identified with the biotechnology because it is this subset the one that has become commercially relevant, which in turn has contributed to push forward the pharmaceutical side of the industry (mostly in form of generics for the domestic market). Again, this piece uses the terms “biotech” and “biopharma” interchangeably to refer to the Cuban biotech; it makes particular sense for the Cuban case and doing so is compatible with mainstream definitions.

[2] This reference to negative cash flow points to the aggregate results of the biotechnology firms, whose historical performance has been on the whole disappointing in terms of profitability and cash flow. This assertion does not include the traditional pharmaceutical companies, but it has implications for the future of many pharmaceutical firms that are more and more dependent on their biotech subsidiaries, or on their alliances with biotech firms—to the point that they can no longer be definitionally separated.

[3] In 2013 Novartis, received approval from the European Union to market its Bexsero against Meningitis B. The U.S. Food and Drug Administration (FDA) granted accelerated approval in January 2015. The international press has erroneously presented this vaccine as the first of its kind that has successfully fought the condition. Even if the new vaccine is said to be designed for different strains, it is not the first commercially available version—nor, as often repeated by the press, was it the first to be successfully employed in a nationwide meningitis B programme for children. Cuba’s VA-MENGOC-BC®, which also has the potential to fight several strains, has been used in Cuba and other countries for more than two decades with impressive results.

[4] The entity derived from the merger of all institutions of the Scientific Pole in western Havana, the biotechnological side of the industry, and all companies within the Quimefa Group, which represented the traditional Cuban pharmaceutical industry. Quimefa was a state holding created in 2001 devoted to producing small molecules (chemically-based drugs), mostly generics, to substitute for imports.


How thalidomide is effective against cerebral infarction

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Scientists reveal that this dangerous drug could suppress nerve cell death.

Notoriously remembered as a major pharmaceutical scandal approximately 60 years ago, thalidomide caused severe birth defects when many pregnant women took the drug as a remedy for their morning sickness.

In recent years, however, thalidomide and its derivatives have been widely used to treat haematologic malignancies such as multiple myeloma.

Evidence also suggests that thalidomide has a neuroprotective effect, reducing both oxidative stress and inflammatory response, but the exact molecular mechanisms of thalidomide on the brain were unknown.

To investigate, scientists at Waseda University and Tokyo University of Pharmacy and Life Sciences studied thalidomide’s target protein, cereblon (CRBN), and its binding protein, AMP-activated protein kinase (AMPK), which plays an important role in maintaining intracellular energy homeostasis in the brain.

Through their study, they revealed that thalidomide inhibits the activity of AMPK via CRBN under oxidative stress and suppresses nerve cell death.

“We hope that our findings will help with the development of new and safer thalidomide derivatives,” says Naoya Sawamura, Associate Professor of Neuropharmacology at Waseda University and leading author of this study, “to better treat diseases such as cerebral infarction, a type of stroke, which is a major cause of death worldwide.”

Specifically, Sawamura’s research group used cerebral ischaemia model rats of the cerebral artery occlusion/reperfusion (MCAO/R) to examine the effect of thalidomide on infarct lesions caused by cerebral ischaemia and related intracellular signals.

After performing qualitative analysis and assessments on the rats’ physical movements, they found that thalidomide treatment significantly decreased the infarct volume and neurological deficits in MCAO/R model rats, and that AMPK was the key signalling protein in the mechanism through additional experiments.

Moreover, to determine the molecular mechanisms of the effect of thalidomide on neuronal death, they used oxidative stress-induced neuronal cells, which were induced by administration of H2O2, as cerebral ischaemia model cells.

“In these cells, we found that the AMPK-CRBN interaction weakened and phosphorylation of AMPK enhanced, but thalidomide treatment restored the AMPK-CRBN interaction and suppressed phosphorylation of AMPK,” explains Sawamura.

“What this implies is that thalidomide regulates AMPK-CRBN interactions in cells under ischaemic conditions, meaning, it can suppress nerve cell death.”

Further study is needed to identify effective thalidomide derivatives with fewer side-effects, as well as more stability because they undergo hydrolysis spontaneously and rapidly in aqueous solutions.

Nevertheless, Sawamura is excited about the future possibilities of this study.

“Our attention is now on the functions of CRBN as a stress response molecule. The suppression of nerve cell death by thalidomide perhaps occurs because CRBN’s function as a stress molecule is somehow enhanced.”

“We want to elucidate the response of cereblons in ageing and stress models to see if decline in the CRBN function could be a biomarker for ageing and stress.”


Sanofi, Evotec in major infectious disease R&D transfer and license deal

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

Big Pharma Sanofi and German CRO-biotech drug discovery hybrid Evotec are penning a deal that will see Sanofi license out a host of infectious disease assets to the biotech, with 100 staffers also moving into its R&D engine.

Sanofi is paying a one-time, upfront fee of €60 million ($74 million) to Evotec, a small sum, but one backed up with a promise to “provide significant further long-term funding to ensure support and progression of the portfolio,” although exact financial details were not shared.

The deal drills down like this: Sanofi will license most of its infectious disease (ID) research and early-stage portfolio (around 10 assets all-told) and move this unit, with around Sanofi 100 staffers alongside it, into Evotec (although this does not include the French pharma’s vaccine R&D unit).

Evotec, which does its own research and also relies heavily on external collaborations with biopharmas and academic biomedical research, will run this “open innovation platform” near Lyon, France, where Sanofi Pasteur is HQ’d.

Sanofi holds on to certain option rights on the development, manufacturing, and commercialization of anti-infective products and will “continue to be involved in infectious disease through its vaccines research and development and its global health programs,” it says in a statement.

The focus of the Evotec drug discovery will be on “new mode-of-action antimicrobials,” the pair say.

Werner Lanthaler, Ph.D., CEO of Evotec, said: “Since the acquisition of Euprotec (UK) in 2014, Evotec has had a significant strategic interest and demonstrated expertise in infectious diseases research, with an ambition to grow and become the drug discovery and development leader in this space together with its partners.

“We are pleased to be working and expanding our strategic relationship with Sanofi, which has a long history in providing novel anti-infective agents to markets globally. Finding a way to motivate more public funding and academic initiatives for the progress of novel anti-infectives on Evotec’s platform will be a key success factor for this initiative.”

The deal is still being talked over, but should be done in the coming months.

Evotec already has a series of deals with the likes of Eli Lilly, Tesaro, Oxford University, and even has its own spin-out in the form of Topas Therapeutics.

Elias Zerhouni, M.D., president of global R&D for Sanofi, adds: “Research in the field of anti-infectives is an area where building critical mass through partnering is particularly important. This new French-based open innovation center will benefit from the high-quality science ecosystem. Evotec is a trusted partner in drug discovery and has the ambition and capacity to become a real leader in the fight against infectious diseases.”

This also comes as Sanofi continues to retool its R&D, getting back into cancer as well as blood disorders via its $11.6 billion deal for Biogen spin-out Bioverativ.


Diabetes tablet passes Phase III clinical trial

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

As rates of diabetes continue to rise, the hunt for new drugs to tackle the metabolic disease is imperative.

In 2014 there were an estimated 422 million people with diabetes, compared to just 108 million in 1980.

Although there are a range of treatment options available for type 2 diabetes, many target the symptoms rather than the root cause and may have adverse side effects. A further difficulty is the close connection between diabetes and obesity, which is causing cases to increase.

Novo Nordisk’s semaglutide however permanently lowers blood glucose levels by increasing insulin production and could also treat obesity, a major underlying cause of diabetes. A recent study showed that the drug controls appetite and food cravings and could therefore generate significant weight loss.

First developed in 2012, an injectable version of semaglutide is already approved for use in the US. Now, an oral version of the drug has now passed its first Phase III clinical trial.

Semaglutide works by mimicking the action of a hormone (GLP-1) which increases insulin secretion. It can be taken orally once daily and in this 6-month trial was delivered in 3, 6 and 14 mg doses to over 700 people with type 2 diabetes.

The drug showed significant reductions in long-term blood glucose levels compared to placebo at all doses, while the highest dose also led to significant weight loss. People treated with 14mg semaglutide experienced a weight loss of over 4 kg on average.

The drug was also safe and well tolerated, causing only nausea, which reduced over time. Chief Science Officer of Novo Mads Krogsgaard Thomsen said he was encouraged by the results of the trial, adding “[The results] confirm the unprecedented oral efficacy of semaglutide that was reported in the phase 2 clinical trial in type 2 diabetes”.

There are nine additional trials running for semaglutide with over 9000 participants, results for which will be provided later this year. Novo Nordisk plan to apply for regulatory approval for the drug in 2019.


Green Leaf Farms receives expanded cultivation site approval

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

US manufacturer of cannabis products has begun operations in a state-of-the-art facility.

Green Leaf Farms, a US-based manufacturer of medical and recreational cannabis products, has received approval for expansion of its state-of-the-art facility and commencement of operations in an additional cultivation site.

Both sets of permits were tied together, the company said, due to the complexity of the structural and mechanical engineering that was needed to integrate the operations.

Based in Denver, Green Leaf Farms is a Division of Player’s Network (PNTV). The company took home the approved building permits for Phase Three development of its production and cultivation build-out, and officially began operations in an 8000 ft2 cultivation room. The site was completed last November.

According to PNTV, the expanded building has been designed to develop new products that will differentiate Green Leaf Farms in the emerging legal marijuana industry.

The expansion includes a state-of-the-art cleanroom, genetics lab, development laboratory, an extraction facility, a commercial kitchen, product development space, automated water purification including custom dosage and nutrient centre, a bio-testing facility, curing, packaging, and media centre.

“These design approvals will allow Green Leaf Farms to complete its build-out and become what I believe will be among the most advanced marijuana production and cultivation facilities in the world,” said Mark Bradley, CEO at PNTV.

“We have combined technology with an amazing, creative workspace that will encourage innovation, product development, differentiation and operating efficiencies.”

Green Leaf Farms has announced that further details of the expanded cultivation and manufacturing facility will be disclosed in due course.


The third wave of AI in pharma R&D

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

The capabilities of artificial intelligence are advancing and its ‘third wave’ offers the ability to analyse enormous sets of data, identify patterns, and generate algorithms to explain them, to the benefit of researchers.

The digital revolution vastly accelerated the research, development, and production of new drugs. Digital technology has augmented the natural capabilities of researchers and scientists in a variety of ways. Now, artificial intelligence (AI) is poised to take this augmentation to the next level.

One of the most significant ways in which AI technology augments human capacity – particularly in an R&D context – is by automating repetitive, lower-level cognitive functions that once had to be carried out manually. This liberates drug researchers to focus on higher-level thinking. This advantage was identified early in the development of AI technology by J C R Licklider, who wrote back in 1960 in Man-Computer Symbiosis:

“About 85% of my ‘thinking’ time was spent getting into a position to think, to make a decision, to learn something I needed to know. Much more time went into finding or obtaining information than into digesting it.”… “Several hours of calculating were required to get the data into comparable form. When they were in comparable form, it took only a few seconds to determine what I needed to know.”

A related idea was expressed by Herbert A Simon with the concept of ‘bounded rationality. He wrote that humans’ decision making can be optimised when they are provided with a limited quantity of relevant, focused information and sufficient time to process it.

With the advent of contemporary AI technologies, the bounds of human rationality have been expanded. AI provides drug researchers with a greater breadth and depth of data that is simultaneously more focused and relevant than the data sets of the past, enabling researchers to optimise their decision-making capacities.

The continued advancement of AI will augment humans’ power of critical thinking in three key areas that are relevant to the medical and pharmaceutical industries: computing advanced mathematical problems, analyzing complex statistics, and generating novel hypotheses. These areas correspond to the ‘three waves’ of AI development throughout the 20th and 21st centuries.

The first and second waves

The first wave of AI development brought us ‘knowledge engineering’ optimisation programs, which solved real-world problems efficiently.

While applications specific to the pharmaceutical industry were scarce, the broader medical field benefits from first-wave AI technologies every day. Take the Framingham Risk Score Calculator, which utilises AI to predict the heart disease risk of any patient.

Machine learning programs were brought along by the second wave of AI. These solve complex pattern recognition problems using statistical analysis. Unlike their first-wave predecessors, second-wave AI programs perceive and learn – often as well as humans do.

Clinical decision support systems use second-wave pattern-recognition programs to analyse and evaluate medical test results. Similar machine-learning programs are beginning to be used by leading pharma firms in a variety of research and development contexts to predict drug effectiveness, to discover new compounds with pharmaceutical qualities, and to develop new combinations of existing drugs.

Second-wave AI is powerful, but it demands well-organised, consistently-coded, and complete data sets in order to accurately conduct its analyses. This limitation is now being overcome by the third wave of AI.

The third wave

We have now entered the third wave of AI development. Third-wave AI programs have the capacity to analyse enormous sets of data, identify patterns, and generate algorithms to explain them. These programs normalise the context of disparate data points and generate original, novel hypotheses at a faster rate and with greater accuracy than human researchers can.

Only in this third wave have AI programs reached a sufficiently advanced state to effectively analyse the vast and complex web of unstructured biological data. Until recently, biological data had to be manually cleaned and organised through extensive and costly human effort. Now, AI programs use a combination of machine learning, natural language processing, and text analytics to analyse unstructured data in real-time.

Through context normalisation, third-wave AI technology dramatically increases the quantity of data that can be analysed in the course of the drug discovery and testing process. Furthermore, it enables the simultaneous generation and testing of new hypotheses at a rate that would be impossible without such immense computing power.

Aided by this technology, drug researchers can arrive at a higher quantity of more accurate hypotheses and can test these hypotheses with unprecedented speed. The result is a significantly faster, and less expensive, discovery process, with lower risk and more effective results. Firms such as Pfizer and Johnson & Johnson are employing such methods to great effect.

Given that R&D consumes as much as 20% of pharma firms’ revenues, and that the total price of developing a new drug has ballooned by 250% in the last 30 years, it’s not surprising that firms are eager to embrace third-wave AI as a means of accelerating drug development.


Amryt looking to expand rare disease franchise

Wax Selection – Leaders in Pharma, Biotech & MedTech Recruitment

UK-based specialist Amryt Pharma is looking to expand in 2018 after acquiring two rare disease treatments.

A relative newcomer to the niche rare disease market, Amryt Pharma was founded by former Astellas medical director Joe Wiley and financier Rory Nealon in August 2015, who spotted an opportunity to develop products in under-served orphan disease therapy areas.

The Irish duo in-licensed their first product, Lojuxta from Aegerion in December 2016, and have since increased its revenues by more than 50%, as well as building a corporate team and European operations.

Lojuxta is licensed to treat the rare, life-threatening disease called Homozygous Familial Hypercholesterolemia (HoFH), and Amryt has marketing rights for the drug in the EEA region, as well as Israel, Turkey and MENA markets.

The company also has in its pipeline AP101, a promising product candidate currently in a pivotal trial for epidermolysis bullosa, a rare and debilitating skin condition.

Amryt expect to bring the product to the US and European markets by 2020, and believe the global market to treat the condition is worth around $1 billion annually.

“This is an exciting time of growth and expansion for us. Rare disease companies often start up in the US and then enter the European market, but our origins mean we have a deep understanding of what’s required and the nuances of doing business in the pharmaceutical space in Europe,” said Joe Wiley.

“I believe we’re proving this with the significant growth we have delivered in the space of one year with Lojuxta.”

The privately-held company is expected to look for further growth this year, and this includes interest in further in-licensing deals.

Meanwhile, the company is planning a paediatric study for Lojuxta and is currently awaiting sign off for its study design from the EMA.

The company is also pursuing additional licences for AP101.

“We’re planning to study other severe partial thickness wound conditions, such as Toxic Epidermal Necrolysis (TENs) / Stevens Johnson Syndrome (SJS), a rare, serious disorder of skin and mucous membranes. These are being planned in parallel in order to maximise the potential value of the AP101 asset for Amryt, our shareholders and most importantly for patients.”

Plans to enter US market

As for expansion into the US, the company says it already has its first “boots on the ground” in the US and in Latin America, its teams there establishing the opportunities in the market and meeting with relevant stakeholders.

“The EB market is particularly appealing in the US – there are approximately 20 centres focusing on EB, therefore it makes it easier for a small, agile company like Amryt Pharma to work closely with them,” says Wiley.

“We can offer patients what they need as we seek to improve their quality of life, with more effective wound care.”

The design of the global trial for AP101 has already been agreed with the FDA, and the company is currently completing the pre-clinical package and preliminary safety data set the US regulator has requested in order to open the IND specific to the US.

Amryt won’t have the EB market to itself, however, and a number of companies are developing novel treatments for the condition.

These include US-based Fibrocell Science, which has just got the green light to begin phase 2 trials of its gene therapy candidate FCX-007 for recessive dystrophic epidermolysis bullosa (RDEB).

Another company in the field is Netherlands-based ProQR Therapeutics, which is working on an RNA-based therapy for dystrophic epidermolysis bullosa (DEB).

Interim analysis of the data from Amryt’s EASE trial will be available later in 2018, followed by top-line analysis.

The company expects to compile its submissions to the FDA and EMA shortly thereafter, with marketing authorisation in Europe and US anticipated late 2019, or possibly early 2020.