Thirusha Lane, from Alnylam Pharmaceuticals, reflects on her 15 years as a nurse and patient advocacy professional in the ATTR amyloidosis space. She celebrates the scientific and therapeutic advances she has seen, and increased disease state knowledge, awareness and advocacy. Thirusha also describes the community’s remaining and emerging unmet needs

I first came across amyloid as a disease-causing entity back in 2005. I was working as a nurse in multiple sclerosis research and studying part-time towards a master’s degree in neuroscience.

Although I had learnt about amyloid during my studies, I hadn’t previously come across amyloidosis in my nursing career. Amyloidosis is the disease syndrome caused by amyloid depositing in the organs, leading to dysfunction and eventually organ failure. I clearly remember those first conversations with patients with hereditary/variant ATTR (hATTR or ATTRv) amyloidosis and their family members in 2008, when I took up the post of lead nurse at the UK National Amyloidosis Centre. I was truly moved by their stories, their courage and resilience in the face of this relentlessly progressive condition. The impact of the disease on all aspects of life—for the patient and for their caregivers and families—was apparent. I remember being confused and frustrated by the limited treatment options and lack of supportive care.

Fast-forward 15 years to 2023 and the present looks bright. The ATTR amyloidosis landscape is barely recognisable from the bleak one I entered in 2008. So, how is it different?

There are more treatment options than ever before. Eight biotech and pharmaceutical companies are involved in drug development for ATTR amyloidosis—an extraordinary number considering amyloidosis is still largely considered a rare disease. To date there are five medicines approved across different countries and regions for the treatment of ATTRv amyloidosis, and several more are in development. Whole new classes of medicines have emerged. There are published therapy and monitoring guidelines from the International Society of Amyloidosis (ISA), a non-profit organisation whose membership mainly comprises physicians and scientists involved in amyloid and amyloidosis research, education or clinical practice. Pharmacological developments and introduction of guidelines for healthcare professionals (HCPs) mean that people living with ATTRv may now dare to be hopeful.

We now know so much more about what ATTR amyloidosis is and is not. Previously, patients with ATTRv were classified under the diagnostic labels of familial amyloid polyneuropathy (FAP) or familial amyloid cardiomyopathy (FAC); these were seen to be discrete conditions. Increased understanding of the underlying pathological mechanism has led to recognition that we are dealing with a single disease (renamed in 2018) associated with a spectrum of manifestations which evolve over time. For example, the V122I variant, previously thought to affect only the heart, is now known to be associated with nerve involvement in some people too, and often the nerve problems can show up many years before the heart symptoms appear. Not only can the symptoms of organ dysfunction start and evolve differently in different individuals with the same genetic variant, but this variability can exist even within families. Why is all this important? Because the ability of HCPs to spot “red flag” symptom clusters is key to shortening diagnostic delay.

Awareness of ATTR amyloidosis among HCPs and patient and advocacy communities has rocketed in the past five years; this is largely due to collaborative efforts among the advocacy, medical and pharmaceutical communities to provide a host of multichannel educational opportunities and materials for HCPs and patients. This increased awareness among HCPs is evidenced by the almost doubling of attendees of the biannual ISA Congress between the 2016 Uppsala meeting—approximately 650—and the 2022 Heidelberg meeting—1,088 (representing 50 countries!). In fact, registration at the Heidelberg meeting had to close weeks earlier than originally planned as capacity had been reached.

In addition to more HCP involvement in the ATTR amyloidosis space, there are more patient advocacy organisations (POs) than ever before (see Table 1). Whilst many of these are small patient and volunteer-led groups, they are growing in capacity and capability year on year. As the world moved into virtual communications during the pandemic, so did the national amyloidosis POs—amalgamating into a global alliance, some with sophisticated websites and a strong social media presence. Some POs are generating real-world evidence from their communities; an example being Sweden, where a community survey led by the PO challenged previously published data in relation to the incidence of some symptoms. Patient groups in New Zealand, Ireland and Canada organised their first ever national ATTR amyloidosis congress, bringing HCPs from all relevant specialities together for the benefit of patients and their families in their respective countries. The Amyloidosis Alliance, the international umbrella association comprising over 20 national POs, organised the first World Amyloidosis Day to raise awareness of the remaining unmet needs in ATTR amyloidosis.

A cumulative result of all of the above is that patients are generally being diagnosed earlier in the disease course than ever before, therefore having access to better care and information, and are living longer. Now that there are treatments available, the conversations that are being had between HCPs and patients in clinic are very different from the ones I was having in 2008; they can now be more positive for those living with the condition at present, and more so for the coming generations as more innovative medicines potentially come to clinic.

Whilst the future for those living with ATTR amyloidosis certainly looks brighter than ever before in 2023, there remain some areas of unmet or only partially met needs. A European Stakeholder Group comprising POs and HCPs came together in 2021 to highlight these; they created an infographic (see Figure 1) and followed with a White Paper, drawing attention to where gaps remain. There are real opportunities here for all stakeholders to work together to move the needle further. In particular, the patient/PO and HCP landscapes are now optimal for coming together around the table to tackle these remaining unmet needs together.

There are also new needs which demand urgent attention. As patients are now living longer, they require a more integrated, holistic approach to their care—one which takes into consideration the “whole person” and their family too—with the goal of preserving independence and quality of life, providing the tools people need to live well with ATTR amyloidosis.

And, following scientific advances, the pressing challenge is to agree on what worsening (or “progression”), looks like in ATTRv amyloidosis, from both the HCP and patient perspective. Are the current range of tests adequate—objective and sensitive enough—to detect worsening, thereby triggering a change in therapeutic approach for patients and those who carry the disease-causing variant but aren’t as yet affected.

Today the amyloidosis community is stronger than ever before. If we can unite with the aim of achieving the same calibre of progress over the next 15 years as we did in the last, the future is not just bright, it’s dazzling.

Table 1: International ATTR amyloidosis patient organisations

Organisation	Country	Year founded
Associaçao Portuguesa de Paramiloidosis	Portugal	1979
Famy Vasterbotten	Sweden	1983
Brazilian Association of Hereditary Amyloidosis Associated with Transtirretina	Brazil	1989
Mitisirube no Kai	Japan	1989
Association Française Contre l’Amylose	France	1994
Asociación Balear de Enfermedad de Andrade	Spain	1997
Asociación Valverdeña de la Enfermedad de Andrade	Spain	2001
Famy Norbotten	Sweden	2002
Tanpopo no Kai	Japan	2003
Amyloidosis Support Groups	United States of America	2005
Amyloidosis Foundation	United States of America	2007
Canadian Amyloidosis Support Network	Canada	2011
Associazione Italiana Amiloidosi Familiare	Italy	2013
Stichting Amyloïdose Nederland	Netherlands	2013
Patientenverband Familiäre Amyloid Polyneuropathie	Germany	2016
Amyloidosis Association Israel	Israel	2016
Fundacion de Familias con Amiloidosis en Mexico	Mexico	2016
UK ATTR Amyloidosis Patients’ Association	United Kingdom	2017
AMILO	Spain	2018
Funcolehf	Colombia	2018
Hereditary Amyloidosis Korea	South Korea	2018
Leben mit Amyloidose	Austria	2019
Amyloidosis Alliance	France/International	2019
TTR Amyloidosis Canada	Canada	2019
New Zealand Amyloidosis Patient Association	New Zealand	2019
Amyloidosis Ireland	Northern Ireland & Republic of Ireland	2020
Amiloidosis Argentina	Argentina	2020
AAN Patient and Family Advisory Committee	Australia	2021

The list above is not exhaustive. Inclusion on the list or omission from it does not reflect an endorsement or otherwise of that group by RARE Revolution or Alnylam Pharmaceuticals.

Acknowledgements

Congress attendance numbers were kindly provided by the International Society of Amyloidosis.

Unmet needs in hATTR infographic shared with permission of the European Alliance for Patient Access.

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NP-UK-00201 – March 2023

This digital spotlight has been made possible with financial support from Alnylam Pharmaceuticals. All opinions are those of the contributors.

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