The fight against Zika: Harnessing partnerships and innovative production processes

Here we explore Takeda’s efforts to develop a Zika vaccine and the crucial role vaccine development programs play in tackling emerging diseases. Laurence De Moerlooze, Vice President & Global Lead Zika, Takeda Vaccines; Gary Dubin, Senior Vice President and Head of the Global Medical Office, Takeda Vaccines; and Rahul Singhvi, Chief Operating Officer, Takeda Vaccines, underline the importance of partnerships and innovation in Takeda’s efforts.  

In 2015 and 2016, an outbreak of Zika virus spread rapidly from its epicenter in Brazil to a number of countries across the Americas. Infected travelers carried this virus to other continents but luckily didn’t cause major outbreaks. First identified in humans in 1952[i], Zika is primarily transmitted by the bite of an infected mosquito in tropical and subtropical regions, which usually bite during the daytime but are also active in the evening and at night. The virus can also be transmitted from mother to fetus during pregnancy as well as through sexual contact, transfusion of blood, and organ transplantation.[ii] For most people, a Zika infection is minor and may cause mild illness. However, during the recent outbreak, Zika was linked to the devastating birth defect microcephaly (where the baby’s head is smaller than normal) and other congenital brain abnormalities, as well as miscarriage and the rare nerve disease Guillain-Barré syndrome. As these serious neurological associations became apparent and with the number of cases rising fast, a global public health emergency was declared by the World Health Organization (WHO) in 2016. With no available vaccines, the crisis called for a coordinated and collective response from the vaccine research and manufacturing community.

Takeda, having expertise in the Flavivirus vaccine field acquired through the ongoing development of a vaccine candidate for dengue, believed that this could be leveraged to support a rapid, collaborative response to the outbreak of Zika, a mosquito borne Flavivirus. By partnering with the Biomedical Advanced Research and Development Authority (BARDA), a U.S. Department of Health and Human Services office, Takeda was able to develop the vaccine candidate TAK-426. It entered a Phase I trial within 15 months of initial development, joining a number of other Zika vaccine candidates. Gary Dubin explains: “Application of a well-established platform, the inactivated virus approach used for other licensed Flavivirus vaccines (such as tick borne encephalitis virus and Japanese encephalitis virus vaccines), gave us a higher probability of technical success in addressing the problem urgently.”

In developing vaccines, pharmaceutical companies often face barriers that require innovation to overcome. As Dubin explains: “It was clear that there were substantial challenges as Zika was a relatively new emerging virus. There were limitations in the medical community’s knowledge and in the availability of reagents and assays that were needed to allow detection of the virus.” This is where working collaboratively with a number of organizations was key to success.

Partnerships are crucial to the innovation demanded from the pharmaceutical industry. For Takeda’s Zika vaccine development, it was partnership with bioprocess equipment manufacturers that enabled Takeda to increase productivity and reduce cost of manufacturing while maintaining high quality in its vaccine candidate.

As is often the case, circumstance also played a role in the development of the vaccine candidate, alongside expert knowledge, partnerships and innovation. As Rahul Singhvi shares: “We had manufacturing capacity in the company that could be deployed to rapidly establish a commercial-scale manufacturing operation for our Zika vaccine candidate. That helped our proposition to BARDA for a rapid response.”

Public health emergencies encourage collaboration and innovation from regulators, too. In January 2018, the U.S. Food and Drug Administration (FDA) granted Takeda’s Zika vaccine Fast Track designation. This Fast Track process is designed to facilitate the development and expedite the review of drugs and vaccines for serious conditions that fill an unmet medical need.

Thankfully, WHO declared an end to Zika’s global public health emergency in late 2016 as the outbreak became contained. Whilst good news, this does highlight the challenge faced by pharmaceutical companies in their decision to respond to public health emergencies given the significant costs involved. WHO’s Zika Vaccine Development Technology Roadmap continues to state the vision and strategic goals for a licensed Zika vaccine and Takeda will endeavor to progress its candidate through clinical development. “The much welcomed declining epidemiology of Zika will make wide-scale efficacy testing more challenging. But with experts agreeing that, unfortunately, Zika will return at some point[iii], we have to continue to adapt and innovate as we go along,”  says Laurence De Moerlooze.

Development programs for emerging diseases such as Zika require a special response that cannot afford to follow a traditional drug or vaccine development route. Takeda’s fast response to the global Zika emergency, utilizing prior knowledge and working collaboratively to innovate in the face of a major public health concern, is a great illustration of how innovation and partnerships can help to tackle the threat of emerging infectious diseases.

 

[i] http://www.who.int/en/news-room/fact-sheets/detail/zika-virus

[ii] https://www.cdc.gov/zika/prevention/index.html

[iii] https://www.sciencedirect.com/science/article/pii/S246826671830029X

How smart boxes are helping vaccine makers deliver more

Here we speak with Michaël Attlan, Head of the New Technologies (NT) Platform at Sanofi Pasteur, about how technology is transforming vaccine delivery. Prior to heading the NT Platform, Michaël led Sanofi Pasteur’s Traveler & Endemic Vaccine Franchise. His work in yellow fever, cholera, rabies, and Japanese encephalitis reflects his and Sanofi Pasteur’s commitment to public health around the world.

Vaccine demand has risen steadily for more than 25 years. With a greater range of world-class therapeutics now available, vaccine developers are looking for new ways to meet this demand. “Today’s players have to improve the vaccination experience,” Michaël says, “because people’s decisions will be made not only based on how well the vaccine performs, but also on how convenient it is to allow better handling and distribution.”

Take flu, for example. It’s a seasonal illness, so large quantities of vaccines need to be delivered in a limited timeframe. This puts huge strain on manufacturers and pharmacists. Vaccine manufacturers need to produce millions of doses and then transport them globally in a temperature-controlled supply chain – a costly and complex process. Simultaneously, those handling or administering the vaccine often lack the facilities to store the volume of vaccines required.

Smart packaging is emerging as one of the solutions. Sanofi Pasteur has developed a new, smaller box for the safe delivery and storage of vaccines. CompactBox halves the size of the packaging allowing twice as many doses to be shipped at once, which can then be stored in half as much space. “We decided to make the box eco-friendly, so we removed all plastic. We have also made the box tamper-proof, which gives vaccine handlers and patients more confidence,” said Michaël. “Today, we have a box that is optimized for cold room storage, respects the environment, leads to lower freight costs and fewer planes to ship it worldwide in record timing, and is more secure.”

The CompactBox could be even smaller if it wasn’t for the need to display the vaccine’s statutory information for patients. “The innovation of using digital support helps meet this challenge,” said Michaël, whose team is exploring ways to access product-related details by scanning 2D barcodes or using interactive chips that are integrated into the carton. The idea is that anyone using a vaccine in the future can wave their smart device over the digital feature to reveal important information about the vaccine, including product authenticity and safety considerations. Michaël continued: “One day soon, people will be able to access relevant information related to pharmaceutical products on an internet device. Regulation will also need to evolve to allow access to online information through internet devices.”

The next stage of smart boxes jumps on the trends emerging in consumer retail where the use of digital labeling and information is growing. Technologies like Near-Field Communication (NFC), which allow communication between two electronic devices when they are placed closely together, are commonly used for public transport, banking and retail.

“I anticipate that in the short term, innovative dematerialized technologies for labeling, tracking, and usage information will become commonplace. The pharmaceutical industry and regulators need to jointly anticipate this move,” said Michaël. “The vaccine industry is adapting to these new consumer trends, meaning that we need to do what has been done by leading companies in other sectors, like Nespresso, Apple or Tesla by leveraging new technologies to deliver more value to end users, within the framework of applicable regulations.”

Help wanted in fight against AMR: World Pharma Association wants to see incentives – but also more regulation

Help wanted in the fight against AMR: World Pharma Association wants to see incentives – but also more regulation

This interview was first published on Medscape Deutschland

Antibiotics resistance is a global problem. At the World Health Summit 2017 in Berlin experts issued an urgent call for new developments and more research so as to be armed in the event of any emergency. Yet, so far, there’s far too little happening, comes the complaint. Thomas B. Cueni, director-general of the International Federation of Pharmaceutical Manufacturers & Associations (IFPMA), explains why this ominous development is taking place and sets out his own ideas for solving the problem.

Medscape: Is the industry making too little money out of antibiotics?

Cueni: That’s too simple a way of putting it. The problem is much more complex. First, research into new antibiotics is a scientific challenge. Then, it’s hard to recruit patients for cliincal trials, the restrictions are substantial and development is expensive.

Unlike with cancer medicines, antiobiotics do not yet benefit from any broadly recognized approval procedure that, as early as Phase II, grants approval to very promising drugs. What’s more, investments are risky because the risk that the research will fail is high.

Ultimately, we don’t as yet have a long-term, sustainable business model. Here you have development costs and risks that may be compared with other drugs. But then there’s a new product generating hardly any sales because it must be kept in the cupboard as a reserve antibiotic. The G-20 summit did reach a broad political consensus that there must be financial incentives for investments in R&D into new antibiotics.

Medscape: Government monies that support research in the private sector are to some extent very controversial. What’s your view?

Cueni: My feeling is you’ve got to look at this in a differentiated manner. Nobody can solve the problem of antibiotics resistance on their own. Increasingly, there are partnerships between public authorities and private sector industry as we can see with Ebola or neglected tropical diseases such as tuberculosis and malaria.

But, right now, there is no sustainable business model for antibiotics. Each year, at least one or two new antibiotics are required. Firms that are active in this area must wonder whether this is sustainable given the development costs and risks. What’s more, they have to invest in their plants and equipment (assets).

Today, there’s widespread agreement that regulations in the environmental field are required to prevent businesses from putting huge volumes of antibiotics into the environment, as is happening in India, say. That’s the way resistant pathogens spread out ever more widely.

Medscape: You’re referring to the fact that last Spring journalists discovered that bodies of water around pharmaceutical plants in India are contaminated with antibiotics. In fact, it ought to be entirely self-evident that the industry should not throw antiobiotics down the sink. Why don’t you as an umbrella organisation bring your own colleagues into line when it comes to environmental requirements before launching demands for government regulation?

Cueni: Occasionally, voluntary action has its limits. It’s not enough that five or ten firms say we’ll stick to environmental standards, and then the 50 others say generic antibiotics are so cheap that investments in this field are simply not worth it.

A rethink is required here, whether through regulations in the area of „good production practice“, or through an agreement among buyers who commit to purchasing solely from firms in a position to certify that all their products have been cleanly produced.

This requires them to be transparent about where the raw materials for antibiotics originate. That can’t just be a voluntary arrangement. For, only a few firms would then be involved and the rest wouldn’t care a jot. Here the World Health Organisation and governments must go along with this and commit to purchasing for their health systems only from certified firms that abide by quality standards.

Medscape: On the one hand, businesses act according to the laws of a market economy, on the other they are to be subsidised with public funding. How can this balancing act be sustained without the threat of legal action?

Cueni: I’m fundamentally pretty cautious when it comes to subsidies for research. But in the battle against AMR (antimicrobial resistance) public-private partnerships have a role in basic research and early development.

To really get hold of the new antibiotics we need it seems to me imperative either way to have a system in place that rewards those who do research in a sustainable and successful manner. There’s always the possibility of agreeing on a higher price right at the point of market launch if a new antibiotic is being brought to market so that the manufacturer need not cover this only via its sales revenue.

Medscape: But not every country can pay these higher prices, surely?

Cueni: This issue is unresolved. One must indeed differentiate between developing and industrialised countries and one can well imagine linking incentives for research and development to ‚access’ requirements/conditions. But we simply cannot afford to wait another 20 years before the international community, G20 or WHO have agreed upon a solution.

Certain countries, the USA, Germany, Great Britain and the Scandinanvians, might lead the way. The issue here is not just higher prices but reward for market entry, or a kind of flat-rate fee for a successful development.

Medscape: Getting public funding for new antibiotics is one thing, but public funding for established antibiotics so that they don’t disappear from the market is quite another story. Many doctors in clinics say this problem is just as urgent if not even more urgent.

Cueni: This is a case of shortages and supply bottlenecks because even generic firms producing on favourable terms say they can no longer produce at that price. This illustrates the particular problem of simply looking at cheapness.

There should be greater awareness that quality, availability and environmental constraints are required if one is to combat the build-up of antibiotic resistances. But this also means that the same conditions must apply to all. It’s out of the question that a few manufacturers stick to the rules and the others simply supply at ultra-low prices.

Medscape: Behind closed doors many suspect that perhaps artifical shortages are being created so as to negotiate higher prices.

Cueni: That’s nonsense. I utterly reject such assertions. The problem is akin to that with vaccines: If the pressure on prices is so strong that even the lowest-priced generic firms say we can no longer manufacture at that price then I think it’s out of order to say the industry is at fault.

Medscape: Pharmaceutical companies themselves officially blame supply bottlenecks on quality defects among suppliers of raw materials.

Cueni: This goes hand and hand as well with the price spiral. I represent the research-based firms that are not renowned for acting like cheapskates. So one must wonder if all this focussing on the cheapest possible price has not gone too far. That impacts upon availability, upon quality and upon the build-up of antibiotic resistances.

Medscape: In your view, how can one keep established antibiotics on the market?

Cueni: If one pays a slightly higher price for antibiotics that are already on the market and one wants to keep them there, then this is pretty marginal for overall health costs compared to the risk one incurs if they are no longer there. If one considers the costs of unavailable antibiotics– avoidable deaths, amputations, periods in intensive care because of septicaemia–then one must ask oneself whether the cheapness of an antibiotic is truly the right criterion for fixing its price.

Medscape: What would you like to see so that the political debate around antibiotic resistance finally bears fruit?

Cueni: I think we must all walk that extra mile and think out of the box. The industry is today very open to regulations that guarantee compliance with envioronmental standards and an appropriate treatment of antibiotics. That cannot happen on a voluntary basis, as a „coalition of the nice“ so to speak.

A lasting solution to the problem of antibiotic resistance requires a further discussion about sustainable market incentives. Political leaders at the G20-summit in Hamburg agreed this and we are grateful that Germany is taking the lead. The debate won’t be easy. For countries don’t just want to throw money at industry but to know what they’re getting for it.

Vaccine, interrupted: simplifying regulatory complexity to avoid delays in immunization

This piece was posted as an exclusive for GEN

Vaccines are considered one of the most successful and cost-effective public health interventions, protecting us from many infectious and childhood diseases. In fact, over the past 50 years, vaccines have saved more lives worldwide than any other medical product or procedure.

Being complex biological products, vaccine marketing authorization applications and production follow strict regulatory and manufacturing requirements. For this reason, most vaccine manufacturers generally produce their global supply of each vaccine at only one or two sites – a major difference to the production of pharmaceuticals which in some cases can be less complex and therefore allows many more sourcing options.

After gaining initial regulatory approval, manufacturers may be required to make changes to the product, also referred to as variations. The need for variations can be due to one of many reasons, e.g. to reflect new regulatory standards, new safety requirements, changes to the manufacturing process or updated product labelling information. Such changes require the oversight of national regulatory authorities that allow the continued licensing of the “upgraded” vaccine.

The regulatory requirements for variations to vaccines are increasingly complex and the length of time required for an application review varies from country to country. Some countries, for example, will wait for a reference country approval before initiating their own review. Others may request the manufacturer to produce additional stability or clinical data. Moreover, limited resources can further delay approval times, in some instances resulting in a wait of up to 4 years to complete the approval process. The knock-on effect can be a delay in access to the best available vaccine or at worst the whole supply chain is put at risk.

This leads us to the question, how can we streamline the management of variations, and bring clear benefits to patients, whilst ensuring fair and equitable access to vaccines?

stephen-cookSome headway has been made by the WHO with its vision to encourage countries that are geographically close to pool their resources and work together on the review process. Such efforts are being observed in Africa as supported by the Bill & Melinda Gates Foundation, where neighbouring countries collaborate on post approval reviews.

Manufacturers and regulatory authorities have demonstrated that they can work together to make essential vaccines rapidly available when required to do so. A great example of this was the H1N1 pandemic in 2009, where efforts were doubled to approve and deliver stocks of a new vaccine. Stakeholders need to reflect on these learnings and develop long-term solutions of collaboration that are sustainable outside emergency situations.

One simple idea, for example, may be to create a global system of categorization of minor and major changes, so that minor variations can pass through a fast track notification process, which in turn would allow resources to be focused on faster reviews of more complex variations. Clear categorization of variations is a win-win both in time and energy for industry and regulators, and most importantly it will help in getting improved vaccines to community more quickly.

As countries review their regulatory processes and frameworks, it is advisable to do so by using the available resources and taking a globally recommended approach rather than “going it alone.” The WHO has published new guidance on post approval changes which is available for countries as a reference.

As we can see, progress is being made, yet more actionable ideas need to be developed. Country regulatory authorities and the pharmaceutical industry should consider how they can collaborate better to secure timely and equitable access for all, so that we continue to see vaccines benefit as many people as possible.

An important milestone in the search for an Ebola vaccine

Ebola-vaccine-regimen resizedbisIt seems there is always a new story in the media about an emerging health threat. Right now, understandably, there is significant public concern about the spread of the Zika virus.

But just over a year ago, it was the Ebola virus and its devastating impact in West Africa that dominated the headlines.

The Ebola epidemic in West Africa may have subsided, but not after leaving a huge human cost—over 11,300 lives were lost, tragically, in the outbreak. Far too many families and communities in the countries of Sierra Leone, Guinea and Liberia were devastated.

Today, flare-ups of Ebola continue in the region because the virus can persist in the bodily fluids of survivors. And experts predict that another Ebola outbreak—somewhere in the world—is highly likely. So we can’t afford to move on from Ebola until we develop the tools to defeat it.

That’s why Johnson & Johnson entered into global private-public partnerships with some of the world’s leading health and research organizations to advance an Ebola vaccine regimen in development at our Janssen Pharmaceutical Companies.

The vaccine regimen uses a “prime-boost” regimen, in which one vaccine dose is given to prime the immune system, and then a second vaccine is administered with the goal of boosting the immune response.

Today, we are very excited to reach a key milestone: the publication in JAMA: The Journal of the American Medical Association of a study reporting the first clinical results for the vaccine regimen.

The study, which was conducted in the UK, found that 100% of healthy volunteers developed antibodies against Ebola after being vaccinated, and that this immune response was still observed in all volunteers when they were tested again eight months later.

The research is early-stage, and we have many more studies to complete. But these promising results suggest that the Ebola prime-boost vaccine regimen, if ultimately approved by regulators, could be an important tool in global strategies to help prevent another Ebola epidemic.

The UK study was made possible by our incredible partners, including the London School of Hygiene & Tropical Medicine, the University of Oxford, Inserm (the French National Institute of Health and Medical Research), Europe’s Innovative Medicines Initiative and Bavarian Nordic.

We’re very proud of today’s study results, and of all of our partners. Yes, we have a long road ahead of us, but we will continue to stay focused on this global health challenge until we deliver an effective vaccine for Ebola.

We’re determined to play our part so that the world is better prepared to prevent this devastating disease.

Biotherapeutic medicines: a winning formula for patients

Biotherapeutics play an important role in modern medicine and have a profound impact on patients with serious diseases. A biotherapeutic is a medical product manufactured or extracted from biological sources. Composed of larger and more complex molecules than chemically-synthesized medicines, biotherapeutic medicines require sophisticated production and control processes in order to maintain their safety and efficacy over time.

In recent years, the expiration of patents for many original biotherapeutic medicines has created new opportunities in the market for biologics. These products, referred to as similar biotherapeutic products or biosimilars, are similar to original biotherapeutic medicines in terms of quality, safety, and efficacy.

While biotherapeutic and biosimilar medicines have opened up new avenues for delivering innovative treatments for diseases to patient populations around the world, some regulatory issues still need to be addressed.  These concerns relate to accelerating access to new medicines, as well as improving regulatory oversight, in order to provide patients with the best treatment possible.

Technological advancements in the field of biotherapeutics continue to provide opportunities to treat an increasing number of diseases. However, specific regulatory and evaluation methods necessary to ensure the safety of biotherapeutic products often prevent the timely approval of new medicines.

Regulatory review processes for biosimilars can also be challenging.  An extensive development program, including head-to-head analytical and clinical studies, is necessary to confirm that a biosimilar has similar quality, safety, and efficacy to the originator product.  Regulatory agencies therefore require the resources and time to review the resulting comprehensive dossiers.  In some countries, the regulatory agencies can only start their reviews once a reference country has issued a license, potentially causing further delays to the approval of a biosimilar.

After a regulatory approval, biotherapeutics and biosimilars face ongoing challenges in managing manufacturing and supply networks.  Biotherapeutics are sensitive to manufacturing conditions and regulators will therefore review a manufacturer’s data prior to approving certain changes.  In some countries the procedures for reviewing such changes can delay implementation of important manufacturing and product improvements by years.

To ensure that manufacturers can more efficiently develop and deliver quality, safe, and effective biotherapeutics and biosimilars, regulatory agencies must develop faster regulatory systems.  These reforms, along with more efficient access and reimbursement procedures, will promote the development of new therapies and increase competition for existing biotherapeutics, and enable access to patients who need them.

As more biologic and biosimilar products enter the market, national regulations will need to cover multiple sectors, moving beyond regulatory approval. Due to the structural complexity and sensitivity of biotherapeutics and their ability to elicit immune responses in patients, sound regulatory standards, as well as stnewGPFrong post-market safety surveillance systems, are necessary in order to ensure the safety of patients around the world. Effective oversight in these areas will help improve physician expertise and patient involvement, manage risk, and maximize benefits for healthcare systems.

As a chemical engineer by background, I have worked extensively to address the development, manufacturing, and quality oversight of biotherapeutics.  Biotherapeutic medicines have significantly impacted our ability to treat conditions and save patient lives. As patients ourselves, it is therefore crucial that we address the issues surrounding biotherapeutics in a way that will best benefit patients. Thus, it is vital that regulators, manufacturers, and health systems start collaborating in order to encourage the development of new biotherapeutics and high quality biosimilars thereby increasing access to patients.

 

Cell and Gene Therapies – The Next Transformative Pillar of Medicine

Genes. Chromosomes. Mutations. Today, these terms are as likely to be overheard in a casual dinner conversation as they are in scientific symposia and medical congresses. While the discovery of DNA dates back to 1869 when Swiss biochemist Johann Friedrich Miescher discovered nucleic acid, it was not until James Watson and Francis Crick published in 1953 their seminal paper in Nature that the science of genetics became commonplace and our vernacular was forever changed. Their finding that DNA replicates by separating into individual strands, each of which becomes the template for a new double helix, was heralded by some to be “the secret of life.” Similar exuberance followed the mapping of human genome in 2003 with the hope that we could now identify all of the “bad actors” in our DNA and find “simple” methods to fix them. However, as history teaches us, early science is almost always confounded by frustration, controversy and yes, failure. This has certainly been true for the field of cell and gene therapies.

The early days of gene therapy were befitting a Greek tragedy. Just as the promise of this new approach was gaining acceptance in the late 80s and early 90s, hopes and confidence were dashed in the wake of some devastating clinical setbacks. It seemed that this nascent field of science was on the verge of being extinguished. However, thanks to the unwavering dedication of undaunted researchers and the remarkable bravery of clinical trial participants, the field of gene therapy not only survived, but it has experienced a remarkable resurgence – due in large part to new methods of transduction which have led to better and safer ways to modify genes.

One of those intrepid pioneers, Dr. Carl June from the Perlman School of Medicine at the University of Pennsylvania, developed an approach which utilizes a disabled lentiviral vector to insert a new gene into a patient’s T cells, producing chimeric antigen receptors (CAR) T cells. These reprogramed T cells aim to hunt, bind to and eliminate cancer cells that have a specific antigen on their surface – such as CD19.

The results from Dr. June’s early trials in blood cancer were impressive. They have garnered headlines in some of the world’s foremost peer reviewed journals. They also led to Novartis’ interest in forming an innovative collaboration with University of Pennsylvania to develop and commercialize CART19 (now called CTL019) and conduct joint research on new CAR T cell therapies. In 2014, Novartis established a dedicated Cell & Gene Therapies Unit to streamline this complex process by combining and leveraging our deep capabilities in Clinical Development, Technical Operations, environment to our own broad scale manufacturing facility in Morris Plains, N.J. The cell reprograming center is the first US Food and Drug Administration (FDA) approved Good Manufacturing Practices quality site for a cell therapy. The facility is currently supporting our Phase II multi-center global study at clinical trial sites in the US, and we expect to expand those trials to the EU by the end of the year.

Novartis is leading the vanguard of investment in cell and gene therapies, and since we announced our commitment to this emerging new field, interest has spread like wildfire across the entire industry, energizing others to join the effort and build a new ecosystem. Additional players and different approaches will only lead to more and better therapies, and I am confident that our collective efforts will have a lasting impact on the lives of many who today have limited, if any, treatment options.

Clearly, many challenges still need to be overcome. Cell and gene therapies are not without side-effects or risks, and defined regulatory frameworks are needed to ensure the safety and efficacy of new products and provide sponsors with a clear path to making new therapies available to patients.

So what will the future hold for cell and gene therapies? Could Miescher have imagined where we would be today? We are tantalizingly close to treating hematologic malignancies with a brand new cell and gene-based therapeutic approach, and learning every day how to harness this potential and apply it to solid tumors, organ transplant and genetic disorders, to name a few. Whatever its shape or form, the recent renaissance in this field strengthens my belief that cell and gene therapies will be the next transformative pillar of medicine – becoming as impactful and disruptive as small molecules and biologics once were.

FINAL-G-2014-PIP-infographie

Patient Centricity is Essential to Modern Day Drug Development

Providing new therapies to patients living with unmet needs faster and more efficiently is an industry-wide challenge. A major key to improving the speed cost and quality of drug development is harnessing the insights of the customer – patients themselves.

The traditional model of clinical development has looked at drug development through the lens of a scientist, often primarily focused on a mechanism of action and subsequent clinical endpoints. This model has resulted in larger, longer and more expensive trials. What we are just beginning to understand is how to identify, target and develop in a manner that can most profoundly impact patients and their day to day lives, which may or may not be related to the clinical endpoint.  To better design our trials, research questions and the outcomes studied must be prioritized by patients.  To more efficiently recruit, retain and ultimately deliver clinical trials we must understand the patient perspective. Finally, to better characterize the benefits and risks of our products for health authorities, we must understand how patients’ perceive the burden of the disease and the standard of care.  Patients play the most important role in clinical trials, and therefore are in a position to help make a difference.

Successful clinical development will be found at the intersection of great science and patient centricity.

Merck Serono has chosen to engage with patients and patient advocacy groups during clinical development through a focus group approach. Patients in the focus group represent a cross section of patients living with the disease. Patients afflicted with life-threatening diseases are often motivated by the knowledge that they are making a difference for people with the same condition. Taking this focus group approach allows us to understand the needs and wants of the patients when it comes to clinical trial design, inclusion/exclusion criteria as well as day to day study impact on patients (e.g. site selection, scheduling, etc). Such an approach allows us to learn the individual needs and motivations by region in a given therapeutic area and then incorporate in our clinical trial designs.

This type of patient centricity is only the beginning. New technologies will eventually make it possible to isolate the patients for whom the drug in development will work.  This will be a paradigm shift in the way clinical development is conducted. Patient centricity will give way to “individual centric” clinical trials with the development of and proliferation of predictive biomarkers and tumor profiling through the collection and testing of cancer cells to determine their molecular and genetic signatures at tumor banks. Predictive biomarker data along with information collected on the tumor can then be applied to determine the best possible treatment that works with the specific type of cancer cell leading to stratified medicine which can, in fact, replace the clinical development model that is in place today. New technologies have the potential to drastically reduce the number of patients required to participate in clinical trials, making it possible to have trials tailored to individuals.  Ultimately, patient centricity will lead to a more accurate diagnosis, and better treatment selection, which has a much greater potential for a successful outcome for patients.

I am an academic researcher by background, and helping people with unmet needs has always been my main driver. Working with patients directly to improve how clinical trials are run is another way to be closer to the patient and understand their needs to help design the best possible therapy. As an industry, we cannot assume we know what patients need – we need to involve their voice in our efforts.  Clinical development that is built on solid science and supported by principles of patient centricity, which includes simplicity of execution, is likely to lead to getting new therapies to patients in need sooner. That is what the scientists and researchers are looking for: science that can be translated into potential new medicines to serve the patients in need.

To learn more about our R&D strategy, please visit biopharma.merckgroup.com .

European Perspective for Effective Cancer Drug Development and New Forms of Partnerships for Managing Uncertainty

The aims of the European Organisation for Research and Treatment of Cancer (EORTC) are to develop, conduct, coordinate, and stimulate translational and clinical research in Europe to improve the management of cancer and related problems by increasing survival but also patient quality of life. Extensive and comprehensive research in this wide field is often beyond the means of individual European hospitals and can be best accomplished through the multidisciplinary multinational efforts of basic scientists and clinicians.

The ultimate goal of the EORTC is to improve the standard of cancer treatment through the testing of more effective therapeutic strategies based on drugs, surgery and/or radiotherapy that are already in use. The EORTC also contributes to the development of new drugs and other innovative approaches in partnership with the pharmaceutical industry. This is accomplished mainly by conducting large, multicenter, prospective, randomized, phase III clinical trials. In this way, the EORTC facilitates the passage of experimental discoveries into state of the art treatments.

Through translational and clinical research, the EORTC offers an integrated approach to drug development, drug evaluation programs and medical practices.

EORTC Headquarters, a unique pan European clinical research infrastructure, is based in Brussels, Belgium, from where its various activities are coordinated and run.

The EORTC is both multinational and multidisciplinary, and the EORTC Network comprises over 300 hospitals and cancer centers in over 30 countries which include some 2,500 collaborators from all disciplines involved in cancer treatment and research.

The 170 members of the EORTC Headquarters staff handle some 6,000 new patients enrolled each year in cancer clinical trials, approximately 30 protocols that are permanently open to patient entry, over 50,000 patients who are in follow-up, and a database of more than 180,000 patients.

Health care systems and the clinical research landscape evolve continuously owing to increased risk aversion, scrutiny by funding bodies, and costs of clinical trials. In this context, however, current drug development procedures are far from optimal, as exemplified by the late-stage failure of several drugs. The identification of new drugs urgently requires approaches based on a solid understanding of cancer biology, and that will support the design of robust confirmatory trials. The complexity and the costs of drug development are now beyond the knowledge and operational capacity of single organisations, therefore, a drastic deviation from the traditional path of drug discovery and new forms of multidisciplinary partnerships are needed to succeed in this sector. The European Organisation for Research and Treatment of Cancer (EORTC) proposes the use of collaborative molecular screening platforms (CMSPs) as a new approach to tackle this issue. These CMSPs have the advantage of optimizing the expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection.

EORTC has developed a CMSP called Screening Patients for Efficient Clinical Trials Access (SPECTA). The EORTC SPECTA is a European screening programme that aims to ensure efficient clinical trial access for patients with a range of tumour types. SPECTA is an integrated and cost-sharing model developed to address the described concerns relating to the current drug development process. This programme coordinates several SPECTA platforms on a pan-European level with the aim of identifying, at an early stage, specific druggable aberrations and, therefore, to offer specific targeted treatment to patients within clinical trials.

The specta collaborative platform

The SPECTA programme is a fully integrated business model that, as well as comprising disease‑oriented screening platforms also embeds specific initiatives to address both the regulatory challenges and the molecular pathological complexity of cancer. A collection of fora has been created for all stakeholders to meet and discuss for optimal mutualization of knowledge.

  • SPECTApath is intended to address quality-assurance programmes across the disease platforms for optimal biomarker qualification and validation, and is crucial for the involvement of pathologists and molecular biologists.
  • SPECTAreg is a research project that addresses the evolution of the forms of partnerships, looks into optimizing regulatory procedures for these new forms of clinical research and explores the routes to new forms of licensing.
specta a collaboration platform

SPECTA is now currently recruiting patients and EORTC is seeking partnership with the commercial sector to explore new models of drug development.

Forging New Approaches to Biopharmaceutical Innovation in Neuroscience

As a psychiatrist, I have long worked to address mental diseases such as schizophrenia and depression. Experiencing first-hand the suffering and heavy burden these ailments place on people motivated me early on in my career to better understand the underlying mechanisms of these diseases and to help find new treatment possibilities. This is why I have devoted the majority of my professional life to neuroscience preclinical research, patient care, and clinical drug development.

Major depressive disorder (MDD) is the most common mood disorder, with life-changing impact on people such as decreased quality of life, functional impairment, and increased mortality rate.  In fact, suicide related to depression is a major cause of death in industrialized countries.

While we have had antidepressants since the 1950s, in many cases people with depression still are not correctly diagnosed and treated. This can be due to stigma as well as perceived efficacy.

Biopharmaceutical research continues to improve care by developing novel antidepressants but periodically their benefits in daily practice are questioned. Skeptics sometimes argue that new medicines provide only limited additional efficacy over current therapies. These challenges can complicate biopharmaceutical research in psychiatric disorders but also provide me and others encouragement to take R&D to new levels.

We’ve long known the pathophysiology of these conditions involves many biological aspects such as mono-aminergic neurotransmitter changes, stress circuits dysregulation, and many other related disturbances. New approaches and new targets are needed. Innovation is not only associated with testing new targets but also with developing new ways to test. We need to identify clinical signals earlier, with more certainty, and in the right populations.

That is what we, at Lilly, are doing – investigating new targets related to those fundamental changes associated with depression. We have discovered molecules which target new mechanisms of action and might lead to treatment advancements for patients with mood disorders and other psychiatric diseases.

Our development work is still early, but current clinical data for one target are exciting enough that we hope to translate some of our preclinical findings and outcomes from animal models into practical clinical knowledge. To understand the potential benefits of this compound, we applied established technologies such as PET and fMRI. These helped us understand our target receptor and functional implication. Moreover, we used behavioral assessments and neurophysiological tools (clinical biomarkers) –new research tools for us – to identify treatment responses earlier.

The basis for the latter approach is that patients suffering from MDD often have cognitive negative biases. That is, they are more likely to remember negative information and pay attention to negative stimuli than to non-depressed subjects. To identify these markers early, we use behavioral paradigms based on psychological testing, and neuroimaging techniques such as fMRI. Using these experimental tools allowed for more effective signal detection and gave new insights in the mechanism of our compound.

Besides such clinical tools, genetics may help us in the next round of discovery and development to identify new targets in psychiatry and overcome the stagnation in the field.

Do you want to learn more about Mental and Neurological Disorders? Check out the DoYouMind? Campaign

For more information about Lilly’s research, visit this website