Here’s to New Beginnings

Featuring: Annalisa Jenkins, Chief Executive Officer, PlaqueTec; Markus Thunecke, Founding Senior Partner, Catenion; Steve Arlington, President, Pistoia Alliance; Olivier Loeillot, Senior VP, BioProcess, Cytiva; and Elliott Berger, Vice President, Catalent Pharma Solutions.

What were the highs for pharma in 2018?

Annalisa Jenkins: I feel very positive about our scientific progress. 2018 was marked by the acceleration of science, approval of disruptive new therapies and significant new capital entering the sector. The promise of advanced therapies, which leverage our enhanced understanding of biology and disease, was realized with the approvals of CAR-T and gene therapy products – which offer potential cures for devastating diseases. We’ve also seen new vaccines for Ebola, therapies for multi-drug resistant TB and new science addressing HIV infection emerge from collaborations between industry and philanthropy. Many major regulatory systems have also evolved to help deliver promising new medicines to patients faster. And then the translation of academic discoveries into new startups – some of which are receiving major funding rounds – has exceeded all previous records.

Markus Thunecke: For me, one of the big highs was the continued success of cell and gene therapies. There are now several products on the market and a rich pipeline of around 300 products. I expect to hear lots of good news over the next years for patients with rare and life-threatening disease, as well as an increasingly positive investment climate given the many large companies that have been “watching and waiting” when it comes to the cell and gene therapy field.

Like Annalisa, I believe it’s been a very good year for scientific progress as a whole. 2018 saw a high number of FDA approvals: 59 as of December 21, compared to 46 in 2017, and a low of 22 in 2016. Alnylam finally brought the first RNAi product, Patisiran for hATTR amyloidosis, across the finish line. After years of ups and downs, this is a crucial sign for the whole field of RNA therapy. The field of checkpoint inhibitors was also recognized, with the Nobel Prize for Medicine honoring the scientific fathers of checkpoint inhibition in cancer, James P. Allison and Tasuku Honjo. The explosion of knowledge and clinical advances in the field of immune-oncology is one of the largest science-driven success stories the industry has seen in decades.

Elliott Berger: I’d like to add that the number of molecules in the pipeline has also increased from roughly 8,500 molecules five years ago to an estimated 12,000 in the pipeline today, targeting the broadest array of diseases ever. I think it’s really encouraging to see so many accelerated approvals that are helping to bring new therapies to patients faster. There are high points in the manufacturing space, too. For example, in biologics, cell line production titers have increased enormously and the manufacturing process is becoming more efficient. In small molecules, enabling technologies are maturing and helping bring more treatments to patients.

Olivier Loeillot: The immunotherapy market is a standout performer. In just a year, the global pipeline of immuno-oncology products saw a 67 percent increase in the number of active agents, and a 50 percent increase in active drug targets.

I also agree with Elliott; I’m delighted by the innovation being seen in manufacturing technologies. For example, there are prefabricated modular facilities that help cut the costs associated with building new facilities, and end-to-end, semi-automated manufacturing platforms that can help with cell therapy production. The magnificent biomanufacturing process intensification and capacity increase that we have witnessed during the past decade has been aided by flexibility brought about by new technologies in production. It’s now possible to cost-effectively produce small batch sizes, which is important if we are to see more personalized therapies reach the market.

Steve Arlington: Generally speaking, industry critics are quick to say R&D expenditure is rising, output failing and development times increasing, but according to The Life Sciences Innovation Report, a new study from The Pistoia Alliance, development times are starting to stabilize and decrease, and more molecules are coming to market at a stable budget. In other words, the industry is getting better at developing drugs. Another high point is, as the others have mentioned, precision medicine, which is offering new treatment options for rare diseases, cancer and autoimmune diseases.

I am also really excited by the increased collaboration in industry, such as with academia and biotechs. Diversity is absolutely essential to make the most of new science, and the ability to think outside of a narrow knowledge base; none of us were brought up and taught about any of the exciting things coming through today.

And the lows?

AJ: In the high-risk world of drug development, not everything will be successful. The year was inevitably marked by failures of some science platforms and programs. It is bold and courageous to try and then fail, and alas we still have not developed a sector and system that incentivizes and rewards efforts addressing major global healthcare issues. Antimicrobial resistance is a threat to humanity; the opioid abuse crisis in the US continues to take lives on an unimaginable scale; and people living in some countries continue to die every day from preventable and treatable disease. Whilst we celebrate the achievements of remarkable science, we must continue to ensure that the diseases killing people worldwide and threatening our stable and thriving societies can secure support in the hearts and minds of governments and investors.

OL: The industry needs to improve clinical trial success rates. Recently, there have been too many terminations of immuno-oncology phase III studies, and drug development remains risky and costly. It takes an average of 12 years and costs almost $2 billion to bring a drug to market. Going forward, we need better diagnostic tools and biomarkers to identify the right patients for clinical trials and treatments.

EB: Industry’s R&D productivity continues to be challenged. We have seen a large number of failures, even in later stage development, and a less visible but very high attrition rate in early phases.  With pricing under pressure, the high spending coupled with high failure rate is a big issue.  Industry needs to make progress on new approaches to clinical trials and development and formulation. 

MT: As every year, it makes me sad to see the poor public reputation of the pharmaceutical industry. Although the majority of people in the industry want to do good things for patients, society, and their companies, a few bad actors can do massive damage.

SA: In some cases, cancer has gone from being a terminal prognosis for individuals to a chronic disease that can be treated quickly – and the quality of life can be high. More success is being seen every year, but some cancers lag behind. For pancreatic cancer, we seem to have gone nowhere in the last 25 years. We’re also lagging in other key disease areas, such as Alzheimer’s, although we are expanding our understanding.

Regarding Markus’ comment about the reputation of the pharma industry, I’d also add that societal trust of healthcare, in general, is very low. The healthcare payer, provider and pharma companies all get smacked by the media and social media, and there will never be enough money to solve all the healthcare problems of the world. It is a constant balancing act between what a country can afford, and what society wants. In the UK, it was gratifying in 2018 to see the National Health Service and Minister for Health announce that they want to move to an agenda for teaching people how to keep healthy and prevent disease. I published an article (which was widely read and acclaimed back in 1998) about the fact that the NHS and healthcare providers could not survive if people didn’t move to a prevention agenda. We can’t afford to eat what we like, do no exercise, and so on, and expect somebody else to pick up the bill. It’s been plainly obvious, and so one my frustrations has been why it has taken governments 20 years to catch up?

What are the most exciting innovations affecting the (bio)pharmaceutical industry right now?

AJ: We are living in an age that is redefining disease. Our understanding of biology, pathways and new targets is accelerating and leading us to realize the vision of personalized medicine. A major disruptor today – which will continue in the near future – is our increasing ability to gather, curate and analyze huge volumes of data. From basic research through to discovery, into the clinical development and healthcare delivery space, the application of AI techniques is truly disrupting our industry and our ability to deliver on the promise of longer, healthier and happier lives.

MT: I agree; it really is an exciting time. Massive advances in the biological sciences are now happening extremely fast and our ability to interrogate large datasets with AI and other tools has reached levels that were thought impossible just a few years ago. Who knows what 2019 will bring? In terms of standout innovations, I find it hard to choose (which is a great sign!), but I would pick the promise of allogeneic Car-T therapy, simplifying a super complex supply chain and hopefully bringing down costs of goods and, ultimately, price. Allogeneic Car-T requires gene editing, and we have the tools available. CRISPR and other gene editing tools could change the face of the industry, or even medicine itself, over the next few decades, but these tools also raise ethical debates that will need to happen in parallel with scientific ones. Equally exciting is the prospect of Car-T/TCRs or modified versions thereof (with safety switches and so on) in solid tumors – something that has proven extremely difficult because of on-target off-tissue toxicities. The whole field of genetically modified cells in oncology reminds me of molecular Lego. It’s a bioengineer’s dream.

In terms of next wave innovations, I see much promise in the area of auto-immune disease. The massive investments into immuno-oncology will result in knowledge that is also applicable in areas that will require not only activation, but specific dampening of the immune response. Some companies have already started to routinely interrogate both the activation and inhibition of immune-checkpoints, to give just one example.

OL: Like Annalisa, I believe that AI and data will be very important in the future. In fact, data is already revolutionizing the manufacture of medicine. Many pharma companies today are particularly focused on digital manufacturing strategies and automation. This change is also evident when looking at our own, internal processes – we are, for example, running a major manufacturing project at our cell culture media factory in Logan, Utah, that combines lean and advanced manufacturing with software analytics. We are also including advanced data analytics that will help us and our customers to increase the understanding of the relationship between raw material variability and process performance during the manufacture of biopharmaceuticals. The ability to detect and monitor raw material variability through data integration will be an important step to ensuring consistent and predictable biomanufacturing performance.

SA: There are a huge variety of multidisciplinary innovations coming through pipelines, including new technical approaches to antibiotics, biospecific antibodies, effective antibody-drug conjugates, genome science, microbiome science, 3D printing, nanosensors, new imaging methods, machine learning, computational biology… the list goes on. But we must take care not to get into the “continuous motion machine,” where people start adding all of this great science together to come up with something ridiculous. Some believe that machine learning will allow patients to talk to a computer that will safely diagnose them and deliver a prescription – and that this will be possible in a matter of months. We are a very long way off anything like that!

What are the biggest barriers to innovation in the industry?

AJ: Innovation and progress rely upon a culture of collaboration across disciplines and geographies, so ideation can thrive among those who are willing to take risks. Open access to ideas and sharing of science and expertise across the continuum of research and development must be encouraged, and must move beyond the current geopolitical tendency towards nationalism (and physical and political borders). Life science and healthcare professionals will realize their shared purpose if they are encouraged and incentivized to collaborate across public and private government sectors.

MT: One of the largest barriers, in my experience, has nothing to do with the complexity of the underlying science and technology; it is to do with the people, mind-set and culture of biopharma companies. One of the root causes of the R&D productivity crisis in large pharma has been the inability of large organizations to leverage the creative potential of its incredibly skilled work force in R&D. And that’s one reason why most breakthroughs come from small to mid-size companies; and those who are successful find it difficult to maintain as they go through a period of hyper-growth (the story of the current crop of outperformers Gilead, Biogen, Celgene or Regeneron).

SA: The sheer cost for single organizations to discover a target and develop a drug remains a problem – and there are fewer and fewer organizations with the financial and intellectual ability to do this (partly because consolidation in the industry is reducing the number of R&D groups). But, on the plus side, there are many small startup companies, who collaborate with experts to find the best way forward. Here, however, the sharing of data can be an issue. I believe we need more pre-competitive collaboration – and companies need to realize that it is much cheaper and effective to collaborate in an early stage without getting themselves into trouble with anti-competition laws. 

EB: Increasing collaboration must be a priority in 2019. High attrition rates and the associated costs of development continue to hinder the industry, but open innovation could help us to share knowledge and optimize the relatively few candidates that will go on to be approved (and even fewer that will go on to be a commercial success). I think the pharma industry is fortunate in that there are many academic, development and commercial partners worldwide who can help – and there are also a lot of initiatives to improve collaboration. Many big pharma companies today have established open innovation platforms to better foster research. For drug development and drug delivery, we’ve also set up our Applied Drug Delivery Institute. The institute is based on open collaboration and allows partners to reach their own models for collaboration – it doesn’t insist on being a partner or getting in the way of collaboration. The institute has published various articles and has its own publications to help share scientific knowledge.

What other big challenges are affecting the pharma industry?

AJ: Small and mid-sized biotech companies comprise the lifeblood of scientific and medical progress around the world. We must ensure that capital flows into this sector to ensure that preclinical programs and platforms are funded from proof-of-concept through human studies. SMEs are driving the innovation engine and addressing the needs of patients globally. As new capital enters the sector, we need to ensure that we can connect talent and ideas with good quality capital, or too many of the SMEs will be sub-scale and unable to optimize their platforms’ probability of success.

SA: There are challenges and trends that come from outside pharma development, which the industry still needs to understand and somehow react to. Affordability and the pricing of drugs and healthcare come into this category. When it comes to the cost of healthcare, most people criticize the cost of drugs, but the total bill for drugs across the healthcare continuum is usually only around 15 percent. In the UK, it’s less than 10 percent. Drug companies are constantly dealing with the pressures of drug pricing and strong criticism, but everyone should be worrying about the remaining 85 percent of healthcare costs.

EB: From my perspective as an outsourcing provider, I’m seeing a lot of venture capital-backed, relatively small, capitalization companies. In fact, around 75 percent of the pipeline is coming from small and mid-sized companies. These companies do not have the resources of large pharma, although fortunately in today’s industry there are many partner firms who can help – whether for early research, formulation, clinical programs, commercial manufacturing, or licensing and approval.

What can the industry do to improve its reputation?

AJ: The healthcare and life science industry offers daily hope to people globally. Society hears negative stories about pricing, access and profits, and less about scientific discoveries, patient support programs and the vast philanthropy fueled by pharma companies. We need to continue to raise awareness and celebrate the work and dedication of scientists, physicians and life science professionals. So much of what we do is hidden from view. We need to change the dialogue on pricing and access, and work together with societies globally to be part of the solution to ensuring that the work of our R&D organizations and academic collaborators is available to all those in need. We need to shift the notion that our industry puts profits before patients towards the reality of scientific and medical innovation that ensures longer and productive lives as a fundamental human right. 

MT: I agree with Annalisa. Two things are crucial in my view. First, we must do more to educate the public about pharma’s great success stories in addressing unmet need, and the complex networks of academics, biotechs and large pharma that were involved in moving them across the finish line. The cure for Hepatitis C, the fantastic successes in treating certain rare blood cancers through cell therapy, and the durable responses to checkpoint inhibition in some patients with metastatic solid tumors are three good examples – but there are dozens more.

Second, we must condemn unethical profiteering, and we must “walk the talk” when it comes to pricing of drugs or proving their economic value.

SA:  A difficult question. For a start, our industry doesn’t even know how to collaborate between its own organizations and associations. Before we can send a message out, we need to get the different cohorts of industry bodies talking with the same voice; unfortunately, the pharma industry is disparate and focused on intellectual property, which limits collaboration. Pharma companies are all very similar organizations but, once you start digging, you discover that everyone has competing or conflicting objectives. Business models also affect the therapeutic areas that companies target. Why is the pharma industry not spending a fortune on bringing new antibiotics to market? The answer is because they will not be rewarded for doing so. Media outlets and politicians bang on about the lack of innovation in certain areas, but it is within their ability to add incentives and to change intellectual property laws. It is much easier, however, to point the finger of blame at the pharma industry (and in politics, this leads to votes). The trust issue doesn’t squarely sit on pharma’s shoulders – politicians also need to be honest about drug costs and how the system works.

OL: There is a need for greater collaboration across the pharma industry. We should strive to create a more holistic industry with a strong focus on areas of public concern. I would like to see the industry engage more in a public discussion, sharing knowledge and ensuring that scientifically accurate and validated information is out there. We should be informing people about how pharma companies have transformed the treatment of many serious illnesses during the last decade.

EB: There are, without doubt, examples where players and practices have damaged the reputation of the industry. Coupled with the costs associated with high R&D attrition rates and the need to meet shareholder’s expectations, it is perhaps no surprise that there are reputational issues. There are many technologies and partners that can help pharma companies improve R&D effectiveness and reduce cost. In my view, the industry needs to get better at predicting which candidates to advance, and which drug delivery systems will yield better treatments for patients.

However, we also need to celebrate our successes more. So many medicines that have saved millions of lives, from vaccines to antibiotics to painkillers, are taken for granted. New waves of medicines have acted on the central nervous system, offer treatment for viral and retroviral infections (e.g., HIV/AIDS therapies), and have cured or delayed the onslaught of cancers. New biologics-based medicines have been able to mimic or support key features of the immune system and we consistently see treatments emerging for illnesses that had previously been considered undruggable. I think pharma has a much better reputation in the eyes of those patients – and their families – who have been saved from debilitating or life-threatening illnesses.

Where should the industry’s priority lie in 2019?

AJ: In 2019, I hope the global focus of the life sciences industry will be on collaborating globally to accelerate the improvement of population health, wellness, and happiness. I hope we will see marked acceleration in the use of health data to deliver a more productive and effective sector, with new capital and players that are willing to take risks and make bold moves. We will see meaningful advances in personalized approaches to care. The immune system will continue to offer targets for disease prevention and cure. Cells as therapeutics will accelerate, as will the promise of bugs as drugs. And the final frontier of the brain will advance as new therapies for major mental health issues and degenerative disorders finally move through to deliver clinical data that offer hope for millions of people.

MT: Focusing on patients and their needs still is, and should remain, the top priority for the industry. There are literally hundreds of diseases in desperate need of improved therapies. Because of that, the industry has to become better and faster at translating science into differentiated medicines (Paul Janssen used to say “the patients are waiting”). We now have better tools than ever before (both scientific and computational), and with the right organizational model that motivates and empowers people to use their creative force, we can expect great things to happen over the next years.

EB: Certainly there are many ways in which the industry could still improve. I think there is a big win to be had by improving patient acceptance. It is a fact that many patients do not take their medication as prescribed, especially at the very start. Outcomes could be improved by boosting initial acceptance and ongoing adherence, which would also save enormous costs in healthcare. It is entirely within the grasp of the pharmaceutical industry to make a significant difference by focusing on drug product design from the very beginning of development. For example, with the technologies at our disposal today, there is no excuse for presenting patients with a large tablet several times a day to be taken only with food. Dose design was once considered a late phase activity, but must be considered early. This starts with selecting the best molecule variant, the best formulation type, finding the optimal dose form design, and goes all the way through to designing delivery devices and medicine packaging that are truly fit for patients’ needs in today’s busy world.

Our research indicates that only a quarter of R&D groups pursue a systematic approach to patient-focused drug design. The biggest challenge, however, is that the R&D teams making the crucial, early decisions about design may not have enough information on the real-world challenges experienced by patients, caregivers, and providers in administering treatments. We need to do better together.

OL: Supporting increased and better access to potentially life-saving therapeutics should be the number one priority for all of us. In practice, this means faster product development times and strong collaboration between pharma and technology providers. As a wider community, we have the tools and expertise we need to improve the manufacturing process and deliver better medicines. And going forward, our abilities will only be enhanced by new tools, such as digital and artificial intelligence. There are major changes happening in science and drug development that will help to increase life expectancy significantly in the coming decades.

Key Approvals of 2018

January

New drug, Hemlibra, for hemophilia A, the most commonly occurring form of the bleeding disorder (EMA). This is the first new medicine in over 20 years to treat people with hemophilia A with inhibitors in Europe.

February

First medicine, Amglidia, to treat diabetes in neonatal babies (EMA). The drug can also be used to treat newborns, infants and children.

Erleada, the first drug approved for non-metastatic castration resistant prostate cancer (FDA).

March

Trogarzo, a new type of antiretroviral for HIV patients for patients with limited treatment options (FDA).

April

Crysvita, the first treatment for children and adults with x-linked hypophosphatemia (FDA).

May

Doptelet, the first oral drug to treat low platelet count in adults with chronic liver disease scheduled to undergo a procedure (FDA). It allows many patients to avoid platelet transfusion.

Palynziq, novel treatment for the rare genetic disorder phenylketonuria (FDA).

Second CAR-T therapy for the US (Kymriah) approved (FDA).

June

First two CAR-T cell therapies in Europe for the treatment of blood disorders, Kymriah and Yescarta (EMA).

First drug in the US containing a purified substance from marijuana, Epidiolex for the treatment of epilepsy (FDA).

July

First drug for smallpox, TPOXX (FDA).

August

Poteligeo, new treatment for two rare types of non-Hodgkin’s lymphoma (FDA).

First RNAi therapeutic, Patisiran, approved in the US and EU (FDA and EMA). 

September

Libtayo approved specifically for metastatic cutaneous squamous cell carcinoma, the second most common skin cancer (FDA).

October

Dengvaxia, the first vaccine for dengue fever (EMA).

Namuscla for non-dystrophic myotonia (EMA).

November

Fexinidazole Winthrop – the first oral-only treatment for human African trypanosomiasis (HAT) (EMA).

December

Ultomiris, a treatment for paroxysmal nocturnal hemoglobinuria administered via a biweekly injection (FDA).