The Bigger Picture

In In The News by Barbara Jacoby

By: Josh Bramwell


Merck’s Chief Medical Officer reflects on his career thus far and weighs in on the industry’s biggest opportunities and challenges.

As an academic physician, scientist and R&D executive, Steven Hildemann is highly qualified to comment on the big issues and challenges that will define the pharma industry for years to come.

Hildemann’s career trajectory can be aptly described as both medical and clinical, with a strong focus on strategy, capability and organization building. From beginning his career as an intern at the Ludwig-Maximilians University, Munich, Hildemann entered the pharma industry in 1998 as a country Medical Director. He then built a career that would see him occupy leadership positions at Pfizer and MSD before taking up his current post as the Chief Medical Officer at Merck; building and leading Global Medical Affairs and Global Patient Safety.

His favorite career highlights so far include co-developing and launching innovative medicines in life threatening and debilitating diseases; the development of Inspra, starting from initial research with Spironolactone, a 50-year-old generic; onwards to Eplerenone, an innovative and live saving follow-up medicine in heart failure; Bavencio, the novel immune checkpoint inhibitor in the immunotherapy of solid tumors, and the “resurrection” of Mavenclad, after initial regulatory challenges to full approval and launch in Europe and re-submission with the US-FDA.

Hildemann has experienced the fine line between success and failure in R&D but is convinced that the industry is accelerating on a path of change in its operating model to meet future challenges. For example, gene therapy is a burgeoning area with great promise in healthcare and the life sciences, he says.

“It has been 15 years since the Human Genome Project decoded the human Genome. After this enthusiasm came a decade of disillusionment and disappointment, much of which changed last year when we had the first couple of direct gene therapy medicines approved. That fundamentally changes the picture. We now live in the age of gene therapy.”

There is fascinating ongoing work in exploring gene therapy interventions for rare hereditary diseases such as cystic-fibrosis, single-cell anemia and muscular dystrophy and others. Ex vivo gene therapy (CAR-T) is already a reality in hematology and other applications in oncology are being explored. He cites the “elegance” of the new gene-editing technology CRISPR-Cas9 as opening the door to untold possibilities.

Merck is well positioned to take advantage of this new frontier, he says. “We are a global leader in the discovery development and distribution of gene therapeutic tools in our life science division.”

The balance between promise and bioethics
Being a leader in genome-editing modalities comes with profound ethical responsibilities, especially when it relates the genome of an embryo, a living person and mankind itself. “At Merck we are acutely aware of this – and we are acting. Our genome is at the core of our identity and the most intimate piece of information you could possibly share, let alone touch,” says Hildemann.

Merck’s bioethics panel consults independent experts from a range of diverse fields including philosophy, theology, molecular biology and bioethics, to help establish science-based bioethical guidance.  This guidance is translated into binding operating procedures, which are published transparently on Merck’s website, as well as in leading scientific journals.

The emerging role of artificial intelligence brings another layer of complexity. The challenges in the healthcare and life sciences are fundamentally different than in other industries because people’s health and wellbeing is at stake. The marked progress, for example in immuno-oncology, will pave the way for the potential use of AI to treating physicians by using physician support devices at the bedside.

“If you combine the genome sequence of a given tumor in a patient with the explosive amount of information that’s hitting physicians from hundreds of clinical trials being published each year in immuno-oncology alone, it becomes clear that not even the brightest, best-informed physician will be able to digest and master this wealth of data, let alone make real-time, science-based decisions on targeted therapy for his/her patient. Without AI support, it won’t be feasible in the future.”

The escalating costs of R&D remain a threat, however. “As you break down tumors by the molecular mutation load and individual targets, tumor samples and patient populations just get smaller and smaller and it gets harder to find these patients, to the point where making these trials becomes almost infeasible.”

Challenges not problems  
If pharma is to continue to thrive, it needs to “accelerate, upscale, deepen and broaden the dialogue it has with key stakeholders such as the FDA and EMA, with payers, patients and ultimately with society. We are seeing novel industry partnerships and convergence.” says Hildemann.

We need to find more innovative and creative mechanisms to deliver the value and efficacy of its medicines. The rise of real-world evidence and future alternative reimbursement models are steps in the right direction, he adds.

The regulatory landscape also appears to be responding. “We have seen approvals based on well-designed phase 1 studies in oncology in around three years. That’s real innovation.

Pharma also needs to rethink the entire value chain facing the new realities of AI, RWE and industry convergence, he says. Merck is actively seeking cross-industry collaborations because it realizes it can’t master AI alone.

Pharma has a lot to bring to these collaborations, adds Hildemann. “Because of our deep knowledge of human biology and the drug development process. Bioethics, whether it’s in Oncology, infertility, stem cell research or gene editing, will be central to our success and acceptance by our partners and patients.”

The great beyond
As breakthroughs in genome-editing move pharma closer to the realm of prevention, what does Hildemann envision lies beyond medicine?

Prevention will pivot the industry’s focus to health in general, encompassing a person’s entire wellbeing, says Hildemann. The essence of medicine will remain even if the offering, application and interaction may be fundamentally different.  “This is why as an active professor of medicine, I enjoy the privilege of ongoing work with medical students, young physicians and patients. It keeps me grounded and connected.”

The rise of virtual consultancies hints at this future, he says. China is leading the charge in telemedicine, but the rest of the world is catching on rapidly.

If these technological innovations are developed in the right way, says Hildemann, precious physician and caregiver time and resources could be freed up and repurposed in more meaningful ways. In fact, this is already happening, with the diagnostic part of radiology and imaging technologies in general being subsequently augmented by AI.

Hildemann is confident but not complacent. He understands the importance of weighing the risks and benefits of any interventions that ultimately have the patient in mind but need to be grounded in core humanistic values. As biopharma accelerates on its path to new medicines, therapeutic modalities and health offerings, he feels confident that the industry is well positioned to deliver on its contracts with society; to improve and prolong the lives of current and future patients around the world.