An interview with Giorgio Iotti, Vice President, R&D Pipeline & Portfolio, Rare Diseases, Chiesi Group

What is UMN?

In simple terms, an unmet medical need (UMN) is a condition where current therapies are not yet available or are not satisfactory. Addressing unmet medical needs of patients through innovation is at the heart of everything we do.

The concept of UMN plays an important role in decision making from a range of stakeholders, including regulators, HTA agencies, payers, academics and the pharmaceutical industry. It informs investment and the setting of priorities.

Chiesi’s mission is to develop and market innovative therapeutic solutions that enhance people’s quality of life.  We feel a huge responsibility towards patients. This is why we work relentlessly to make sure they receive high-quality drugs leaving no patients behind.

And how does your company consider UMN in R&D decisions?

All our research and development (R&D) programmes start from the identification, in a patient-centric manner, of a UMN coupled with the scientific possibility of addressing it. Indications where there is significant unmet medical need are prioritized because they are seen as therapeutic areas where there is a margin to create value with our therapeutic approaches.

Alpha Mannosidosis is an ultra-rare insidiously progressive disease leading to disabling decline. It is a highly heterogeneous disease with a continuous spectrum of manifestations and severity and enormously challenging to study due to significant development limitations.

What are some of the challenges in the R&D process?  

The biggest challenges relate to patient availability and accessibility for clinical trials. Also designing adequate clinical trials and identifying feasible clinical endpoints or surrogate biomarkers acceptable by regulatory authorities is a challenge.

In indications such as Alpha Mannosidosis, pricing and reimbursement as well as market positioning and value generation also becomes challenging.

How do you decide which disease areas to explore, research, and invest in?

We perform strategic exercises that consider disease features (including UMN, presence of standards of care (SOC),  epidemiology, competitive landscape (including presence of other programs active in the field and stage of development), strategic fit with Chiesi’s vision, trial feasibility and, if a certain modality is considered, developability (in general, including technical feasibility).

Our strategic business objectives have always been centered around innovation and patient care. By investing in rare diseases, respiratory health, and specialty care, we are positioned to address a wide range of healthcare needs. Our research in biotechnology allows us to explore innovative treatments for complex diseases, offering new hope to patients with limited options.

Can you provide an example of how treatments for specific diseases have progressed over the years? 

Alpha mannosidosis is a disease that was discovered in the late 1960s. Only since the early 2000s has the scientific community been active in trying to define the natural history of the disease and identifying a drug that could slow its progression.

In the rare disease field, we have observed that once a clinical trial for a certain rare disease is opened, this generally boosts the knowledge around that disease, including opening of other clinical trials, increase in preclinical programs start etc. With the development of velmanase-alfa came an increase of unconventional evidence generation opportunities from the first Natural History studies (dated 2007) which led to long-term follow-up integrated databases, registry data and compassionate use programs.

Velmanase-alfa development represents a virtuous example of development for a disease with an important UMN. The initial development was supported by a European research consortium and was the first experimental treatment to receive a EU research grant for early clinical trials in the context of the Seventh Framework Program (project Alpha-Mann, FP7-HEALTH-2010-261331). Chiesi acquired the Scandinavian biotech company sponsoring the clinical development (Zymenex A/S) in 2013, established a biotech research center in the Karolinska Institute campus in Stockholm (Sweden) and sponsored the pivotal clinical trials ultimately leading to the approval of this important treatment option in EU, UK, US and several other countries.

Can you share examples of groundbreaking science that is transforming or will transform disease management or treatment?

Gene therapy has the potential to change the scene for some rare disease, since many can be “curative”, resulting in a “once in lifetime treatment”. The development of new cell and gene therapies, from target discovery to market approval, can take as long as 15 years, and often involves a wide range of partners, each contributing in a unique and indispensable way. Advancements in gene therapies will have further impact on patients in the near future with better manufacturing processes, prolonged effects and lower doses. Gene editing is also emerging with the same, if not greater potential impact.

Ultimately, basic research into the genetic and molecular causes of rare and other chronic conditions is associated with significant spillover to other disease areas, advancing care for everyone. With the recent launch of our Biotech Centre for Excellence, Chiesi has a reinvigorated focus on pioneering research and breakthrough innovations that align with global trends.

If you could imagine the best possible future for patients and research in Europe, what would that look like?

The best possible future has shorter pathways towards regulatory approvals of drugs plus more precise, homogenous and harmonized guidelines from the regulatory authorities.

We require more and tighter connections between patients and patient associations, and an improvement and greater uptake of newborn screening programs and early genetic testing across the continent. In terms of newborn screening (NBS) programs, harmonized and standardized procedures and screening panels would assist in fostering greater expansion and uptake.

What support do you need to achieve it? 

In terms of policy, the revision of the pharmaceutical legislation can help reverse some trends by signaling that Europe still believes in the innovative pharmaceutical sector and its ability, in the long run, to revolutionize the lives of many European citizens by offering new therapeutic perspectives. We require a holistic and ecosystem approach. 

The current proposal by the European Commission and Parliament to define ‘’unmet medical need’’ should note that not all patients are the same - whether across disease areas or within the same disease – as some might not respond to or benefit from existing therapies, while others may still benefit from further innovation that offers more appropriate treatments.

Unmet medical needs are not singular or fixed, but rather evolve over time and change as the disease progresses and scientific progress is made. Therefore, the absence of a treatment or therapy is not the only unmet need to consider. The quality of life of patients and their families and caregivers, the burden of treatment and the disease and its severity should also be considered in research and investment discussions concerning unmet medical needs. For Chiesi’s R&D decisions, a broad understanding of UMN encourages continued research for all patient populations who can benefit from therapeutic innovation.

We also need to establish a multi-stakeholder dialogue, building on existing EMA and HTA structures, along the drug development path. It should include patient representatives, developers, clinicians, regulators and HTA experts, that can continuously refine and update existing assumptions on unmet needs.

In terms of the incentives required for orphan drug developers, it is pivotal to that we maintain strong and predictable incentives and intellectual property protection framework for all medicines, and especially for orphan drugs and ATMPs, which require targeted and riskier investments. R&D needs to increase in underserved areas through support mechanisms for basic research and fostering public-private partnership – like the Rare Disease Moonshot - between academics, researchers and industry, as well as the direct involvement of patients.

Besides this, there must be a keen focus on generating and attracting innovation and talents in centers of excellence and companies. Launching an EU Rare Disease Action Plan, to support access to and development of novel therapies, is the priority for this push for innovation, especially for the 95% of rare diseases where no therapeutic options exist.

It is innovation that will be able to provide the answers to future health challenges. It is the innovation that will provide employment opportunities to the future generation of scientists, doctors and technical specialists. It is innovation that gives hope to the hundreds of thousands of people with rare diseases still without treatment or with partial treatments. It is innovation that generates prosperity.