A lifeline for rare disease patients

For more than 25 years Alexion has been blazing a trail in rare diseases, bringing a series of life-changing medicines to market. pharmaphorum’s Richard Staines spoke with Sean Richardson, general manager, UK & Ireland and Charles de Wet, medical lead, UK, Ireland, Nordics & Netherlands, to hear about the challenges developing rare disease drugs, getting them to market, and the life-changing value they have for patients.

Alexion has been developing life-transforming drugs for patients with rare and ultra-rare diseases for more than 25 years.

The company has a wealth of experience and is most famous for the rare disease drug eculizumab (Soliris), which has been approved in paroxysmal nocturnal haemoglobinuria (PNH), atypical haemolytic uraemic syndrome (aHUS) and refractory generalised myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) antibody-positive.

But it has also had other rare disease drugs and indications for existing drugs approved in recent years, and has a pipeline stocked with several other potential therapies.

Alexion’s pipeline includes potential new treatments for copper metabolism disorder Wilson disease, and the neurological disorder neuromyelitis optica spectrum disorder (NMOSD).

In an interview with pharmaphorum, Alexion’s UK & Ireland general manager Sean Richardson outlined the unique challenges of developing rare disease drugs, and the unique opportunities to make a real difference to patients’ lives.

One of the first challenges is to identify the underlying mechanism of the disease and build a knowledge base that can inform any research.

This is much tougher than with more common conditions because there are far fewer patients, and there is often limited to no existing research available.

Trying to set up studies with small numbers of patients also means small numbers of centres located around the world. This poses a completely different set of challenges compared with trials for more common diseases affecting large numbers of patients such as diabetes.

“A lot of our work goes into trying to decipher the pathways of the disease and meaningful clinical endpoints to study, which for common diseases that are better understood is not a step that is required.”

Patient organisations play a key role in this, as they often can help provide insight into the nature of the disease itself.

“You start getting very different insights into the natural history of the disease and also some of the challenges patients face.”

“This can give an indication about the kind of support patients might need relating to how they manage the disease, and the critical areas of focus for any research,” said Richardson.

De Wet said: “It’s only when you really ask patient groups what matters to them that you sometimes realise that you need to address that particular issue. Through this the patient also can feel part of the development of the medicine.”

Given the serious nature of the diseases that Alexion deals with, the company has built a strong relationship with patient groups and works closely with them to ensure research is on the right track.

“Patients with rare diseases are keen to participate in trials, and they will often tell each other about a trial that is due to start, so you will get patients phoning the trial centre to ask whether they can participate.”

Feedback from patients has led to Alexion developing its new longer acting complement inhibitor, which is a successor to Soliris – ravilizumab (Ultomiris) was approved by the FDA for PNH in December and can be administered once every eight weeks, instead of once every fortnight.

Ravilizumab is also under review by regulators in Europe and Japan.

Life-transforming therapies

Richardson pointed out that the value of these drugs for patients can be high, in some cases reversing or staying the progression of what would be a fatal disease if left untreated.

“When we talk about life-transforming, we do not use this term lightly,” said Richardson.

Rare disease medicines can result in fundamental changes for patients, instead of the incremental changes seen in other areas of medicine, he said.

He cited the example of one of Alexion’s other approved rare disease drugs, asfotase alfa (Strensiq), which assists bone formation in patients with paediatric onset hypophosphatasia (HPP), caused by a genetic abnormality where bones do not build properly because of defective mineralisation.

Bones in babies born with this condition are soft and prone to deformation and fracture, and they often do not live beyond their first birthday.

Richardson explained: “The most devastating aspect for infants with this is they don’t form mineralised ribs. Obviously without functioning ribs they are unable to breathe so the respiratory failure can occur quickly. What is amazing is seeing the ribs forming on an infant patient started on asfotase alfa.”

One patient in the initial trial is now more than 10 years old and Richardson said this achievement is “truly astonishing”.

“How do you value that? You have got to look at the impact on the patients and their families, and the lifelong improvement you are getting from the treatment. Yes, the technology is expensive to develop but there is a responsibility between ourselves, policy makers, governments and payers to find a sustainable way of funding treatment for rare diseases.”

Working together for patients

Alexion has been recognised by the NHS and NICE for finding an innovative way enabling patients in the UK to have access to treatment with asfotase alfa – the company drew up a “managed access” agreement with NICE that made the treatment available to all eligible children and adults.

Alexion, NHS England, NICE, clinicians and patient organisations all signed the agreement, demonstrating in Richardson’s opinion the importance of teamwork between stakeholders.

“It’s only when all of you come together that you can find a solution,” said Richardson.

De Wet highlighted the NICE Highly Specialised Technology (HST) appraisal process as a good first step to address the problem of assessing medicines for rare diseases.

But there is more work to be done, with one issue being that it is something of a “one size fits all” approach. Broader values and considerations should be considered, such as the impact of the treatment on the patients’ survival and quality of life, the rarity and severity of disease, and the lack of sufficient alternative therapies.

The clinical trial may also not generate the kind of long-term data needed by cost-effectiveness bodies such as NICE, who may wish to see data showing that the medicine continues to work over a longer period.

NICE and regulators must work together to try and improve the handover between clinical trials and cost-effectiveness assessments, said Richardson.

Patient voice

In his role with Alexion, De Wet said working closely with patients is one of the most rewarding parts of his job.

In rare diseases the medicine under development is typically the only one in development, and the success or failure of the medicine will affect them directly.

“I feel closer to patients than I ever did working in big pharma. Somehow these patients’ whole life story is so much closer to you and the work we are doing.”

One of the company’s values is that patients are its “guiding star”, and De Wet said that working in rare diseases allows him to more closely “walk in a patient’s shoes”.

Including the patient voice in the development and reimbursement process has been vitally important in securing positive outcomes, said Richardson.

Richardson added: “When you look at reimbursement, patients are key stakeholders in the NICE process, whether that’s going through the review or the managed access agreements, they have always been right at the heart of that.”

De Wet concluded:

“I believe they will play an even more important role in research, as medicines become more specialised, and when it comes to market access, which is why I think patients should be given an even louder voice.”

Sean Richardson is general manager for the UK and Ireland at Alexion Pharma UK Ltd. Sean joined Alexion UK in 2015, where he began as a Sales Director and later went on to lead the enzyme replacement therapy portfolio within the Metabolic Disorders Business Unit. With 20 years of experience within the pharmaceutical industry, he is passionate about transforming patients’ lives. He holds a Bachelor of Science in Biochemistry from Bath University.

Dr. Charles De Wet is senior medical director at Alexion Pharma UK Ltd, leading the company’s medical activities in the UK, Ireland, Nordics and Netherlands. Dr. de Wet is a registered medical practitioner with broad experience across all areas of Pharmaceutical Medicine. He has been a member of the ABPI’s Innovation Board and chaired the ABPI’s Medical Committee and later Medical Expert Network. He functions as an Educational Supervisor, Specialty Adviser and Appraiser for the Faculty of Pharmaceutical Medicine and is a Fellow of the Faculty of Pharmaceutical Medicine of the Royal Colleges of Physicians, and the Institute of Directors, London.

Richard Staines is Senior Reporter at pharmaphorum. He has been a journalist since the 1990s and has written for websites, newspapers and magazines. He has always had an interest in health, and has been focusing on the pharma industry since 2010, interviewing industry leaders and covering stories on topics including regulation, mergers and acquisitions, and the latest clinical developments.

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