Ensuring the patient voice is heard with Huntington’s disease

Elevating the patient voice in Huntington’s disease

Published 2 February 2019, updated 9 July 2019

How patient partnership is shaping the future of research and clinical development in Huntington’s disease.

In the traditional drug development model, patients themselves or their representatives are often absent or play a minimal role in discussions about drug development, where scientists, researchers, regulators and pharma industry experts take the lead in designing and developing treatments and trials. Though we may be an expert in developing medicines, no one knows more about living with a disease than patients and their families.

In rare diseases where research and treatment can be as rare as the disease itself, it is even more imperative to work with the community as early as possible to better understand what meaningful benefit means to patients; especially with rare neurological diseases where endpoints are often not clearly defined.

Over 7,000 Rare Diseases worldwide
Less than 5% have an approved therapy

What role can patients play in clinical development?

It is critical that patient representatives have a seat at the table, quite literally. Of the nine external advisors that make up a clinical advisory committee for Huntington’s disease, Cheryl Sullivan Staveley, a caregiver, is one of two family representatives providing the patient perspective. She sits alongside world-renowned researchers, scientists and clinicians where she directly contributes to the guidance and strategy of our Huntington’s disease research programme.

Cheryl at a recent meeting on Huntington’s disease
Cheryl at a recent Roche Strategic Advisory Committee meeting on Huntington’s Disease.

Cheryl is an expert on Huntington’s disease and healthcare in her own right. In addition to being a registered nurse, her husband John died from Huntington’s disease, as did her daughter Meghan from a juvenile form of the genetic neurodegenerative disease. Cheryl also runs two Huntington’s disease support groups and is a widely known and respected advocate in the patient community. “As much as the researchers are in their trenches, patients and families are in the trenches everyday 24/7 - in my case for 30 years. I can provide the family’s perspectives and the personal, human side of Huntington’s disease in our discussions - such as what’s meaningful, realistic or feasible - to help create better, more robust trials,” she says.

She’s playing a critical but uncommon role. As a patient representative, she is shaping the overall strategy of our approach to finding a treatment. But she is also forging a new era in healthcare where patients shape the future of development as equal partners.

Huntington’s disease causes the breakdown of nerve cells in the brain

Huntington’s disease is a fatal genetic disorder that causes the breakdown of nerve cells in the brain. Symptoms affect three main areas:

  • Cognition: losing ability to think clearly and quickly, impaired judgement
  • Behaviour: personality changes, irritability, mood swings, depression
  • Movement: displaying jerky involuntary movements, balance issues, difficulty speaking and swallowing

Living with Huntington’s disease, every day

There is no cure and only one approved treatment, which targets the motor symptoms. However, directly engaging with the patient community reveals that the priority concern is not motor disability; it is cognition and function.

Cheryl explains how preserving cognitive function is an essential element for those living with the disease: “For some people with Huntington’s disease, they may be unaware of how much chorea - which are the motor symptoms - they actually have, and their chorea is less bothersome to them than it is to their loved ones that observe them daily. John and Meghan acknowledged they would have tolerated chorea all day long and stayed a bit more of themselves if cognitively and emotionally they were fine.”

Roche has recently embarked on a pivotal clinical programme in Huntington’s disease. Mai-Lise Nguyen, Patient Partnership Director in Rare Diseases Pharma Research and Early Development (pRED), is working closely with patient groups and representatives and is enthusiastic about the patient-centric approach: “Our teams are really focused on co-creating together with the patient community. We recognise the need as well as the potential that this approach has in order to design better pre-clinical and clinical programmes, move faster and develop more meaningful endpoints - and ultimately deliver a transformative medicine to patients.”

Huntington’s disease causes the breakdown of nerve cells in the brain

Especially in rare disease like Huntington's, it is essential to ensure the patient experience is incorporated into research, development and protocol. Cheryl (centre) and Mai-Lise (left) discuss clinical trial design.

Asking so much from patients

In planning for the pivotal programme, the Huntington’s disease team sought advice on all aspects of study protocol, including how the drug is administered. Current research suggests the use of monthly treatment and, given the type of molecule, the only route of administration is via a lumbar puncture (injection at the base of the spine) to ensure crossing of the blood-brain barrier.

Conscious of the burden of long-term lumbar punctures and overall feasibility, this was an important topic to discuss with the patient and family communities. “It was clear from the community that the priority is to develop a treatment that could stop or slow the progression of Huntington’s disease, regardless the route of administration or dosing frequency. Patients would do whatever is needed to reduce the devastating impact of Huntington’s disease, but if it were possible for a less burdensome drug administration, it would allow for a better quality of life for patients and their families,” Mai-Lise says.

As a result of these discussions, our Phase III pivotal trial will evaluate the use of both every-other-month and every-four-month treatments, compared to placebo. “Though having a three-arm clinical trial introduces additional complexities, it will answer an important question and need of those living with Huntington’s disease,” says Mai-Lise.

Elevating the patient voice

For Cheryl, she also uses her role on the clinical advisory committee to bring a human emotion to the equation. “Scientifically knowing the disease doesn't equate to a real human being or what living, breathing families experience with Huntington’s disease on a daily basis. In the committee we utilise my perspective as a family member and community representative to come up with a better drug, a better plan and the best possible clinical trial,” she says.

Listening to the patient experience for Huntington's clinical trial protocol
“It’s about co-creating together and not assuming what patients and their families want - why not involve them in the process from the beginning,” says Mai-Lise.

With so much at stake

In order to bring meaningful treatments to patients, we need to fully appreciate the mechanisms and impact of a disease on patients and families. In Rare Disease, we are embracing patient partnership across the product lifecycle. By having patient representatives like Cheryl and patient advocacy groups collaborating in decision- making, it allows their knowledge and unique insights to be captured throughout every stage of research and development.

Cheryl points out that “clinical development isn't just scientific knowledge found under a microscope. It’s also is about empathy and understanding the experience of patients and their families to create a better treatment; dare I say a cure. I hope in the future to see the patient community always sitting alongside the scientific community as equal partners from the very beginning.”

Partnership and collaboration are the keys to success: Roche & Ionis Pharmaceuticals

Ionis Pharmaceuticals’ headquarters in California
Ionis Pharmaceuticals headquarters in California.

The patient community plays a huge role in understanding disease and shaping clinical development, but collaboration and partnership with the scientific community also prove essential for success.

Ionis Pharmaceuticals has been a leader in the space of RNA-targeted drug discovery and development. In 2006, together with the University of California, Ionis began developing a treatment for Huntington’s disease that attacks the root cause of the genetic neurodegenerative disease.

Promising research from Ionis showed the the potential to slow the progression of Huntington’s disease through the lowering of HTT levels in the nervous system. In 2013, an alliance was formed between Roche and Ionis based on the promising technology developed by Ionis. At the end of 2017, Roche took over responsibility for all development and commercial activities related to the Huntington’s disease programme.

It further proves that when it comes to successful drug development, partnership is essential.

Tags: Patients, Innovation