Top 10 FAP stories of 2024
Readers sought out stories about treatments for FAP, results from clinical trials
Throughout 2024, FAP News Today informed our readers about the latest developments in treatment and clinical trials for familial amyloid polyneuropathy (FAP).
Here is a list of the top 10 most read stories we published in 2024, along with a brief summary. We look forward to continuing to be a trusted resource for the FAP community in the coming year.
No.10 – Disease-modifying treatments prolong survival in FAP patients
There is no cure for FAP, but disease-modifying drugs (DMDs) and a liver transplant can help slow the disease’s progression. Researchers in Japan found that DMDs — including Onpattro (patisiran), tafamidis, and diflunisal — extended patients’ survival over a follow-up period of 30 years. This effect was independent of the age when symptoms began and whether patients initially presented symptoms of nerve damage (neuropathy). In turn, liver transplant improved survival in patients with early-onset FAP, when symptoms develop before age 50, but not in those in later disease onset and in patients first presenting symptoms other than neuropathy. Future studies are needed to confirm these findings in patients in other countries and regions, the researchers said.
No.9 – Tafamidis meglumine shows greatest benefits at early disease stages
Tafamidis meglumine (sold as Vyndaqel) is an oral therapy approved in Europe and other regions — but not in the U.S. — for FAP. Scientists in Spain showed that, for FAP patients carrying the most common disease-causing mutation, Val30Met, tafamidis meglumine was most effective when given at the very early stages of the disease, when there are noticeable symptoms, but no walking difficulties. Patients with worse disability had a 60% probability of failing to respond to the therapy. The findings suggested that other treatments should be considered for patients with more advanced disease.
No. 8 – Phase 1/2a trial of gene-editing therapy doses first hATTR patient
A Phase 1/2 clinical trial testing YOLT-201, Yoltech Therapeutics’ experimental gene-editing therapy for FAP and hereditary transthyretin amyloid cardiomyopathy (hATTR-CM), a FAP-related inherited disease that affects the heart, dosed its first patient in July. The one-time treatment uses tiny fatty molecules to deliver a gene-editing machinery that’s designed to stop the production of transthyretin (TTR), the protein that’s faulty in hATTR amyloidosis and forms toxic clumps that accumulate in the body’s tissues. YOLT-201 is expected to ease symptoms and slow disease progression.
No. 7 – Second dose of gene-editing therapy NTLA-2001 reduces TTR protein
Data from a Phase 1 trial showed that FAP patients given a second, therapeutic dose of Intellia Therapeutics’ gene-editing therapy NTLA-2001 saw their blood TTR levels drop by a median of 95% after about one month. The three patients had first received a suboptimal, low dose of the therapy that decreased TTR levels by 52%, failing to reach target TTR levels. Also, the second dose was well tolerated after up to one year. NTLA-2001 is designed to prevent TTR production by using tiny fatty molecules to deliver the gene-editing technology CRISPR-Cas9 to liver cells, the main producers of TTR. While it is meant to be a single-dose treatment, the data suggest NTLA-2001 re-dosing, if necessary, would be safe and effective.
No. 6 – Wainua available to FAP patients in US via specialty pharmacy
At the beginning of the year, Wainua (eplontersen), AstraZeneca and Ionis’ liver-targeted therapy designed to reduce TTR production, became available to adults with FAP in the U.S. through a specialty pharmacy called Orsini. Its approval in December 2023 made Wainua the first and only FAP-approved therapy to allow self-administration via an autoinjector. Phase 3 trial data showed that more than a year of treatment with Wainua, given once monthly, was generally safe and reduced blood TTR levels by more than 80%, slowed disease progression, and improved life quality.
No. 5 – Neurological, heart symptoms present in a quarter of ATTR amyloidosis patients
ATTR amyloidosis comprises a group of conditions, including FAP, that are characterized by a buildup of toxic TTR clumps, regardless of whether this is associated with inherited mutations (hATTR amyloidosis) or not (wild-type ATTR amyloidosis). The 15-year THAOS study on the natural history of ATTR amyloidosis, including 6,368 patients in 23 countries, found that about one-quarter of them had a combination of neurological and heart symptoms. Most patients in Europe, Asia, and South America carried the Val30Met mutation, which showed a strong link with neuropathy symptoms. In North America, most patients had wild-type ATTR amyloidosis and showed heart problems.
No. 4 – Diflunisal may have similar efficacy to tafamidis-free acid
Researchers in Taiwan showed that diflunisal, a treatment commonly used off-label for FAP, may be as safe and effective for people with early-stage FAP patients as tafamidis-free acid, which is approved in the U.S. under the brand name Vyndamax for ATTR-CM. By following 57 early-stage FAP patients who mostly carried A97S, the main hATTR-causing mutation in Taiwan and East Asia, they showed both medications equally slowed progression of nerve and heart damage. Based on these findings, the scientists hypothesized that diflunisal may become a cost-effective alternative treatment for hATTR amyloidosis.
No. 3 – Wainua effectively slows FAP progression across patient groups
Subgroup analyses of a Phase 3 trial, whose top-line data supported Wainua’s approvals, showed the therapy slows FAP progression and improves quality of life regardless of patients’ sex, specific mutation, or nutritional status. Wainua was shown to outperform a placebo in terms of disease progression and life quality measures in both men and women, those with early- or late-onset disease caused by the Val30Met mutation, and whether patients gained, lost, or maintained their weight.
No. 2 – Amvuttra may lower heart damage in FAP patients
Phase 3 trial data suggested Amvuttra (vutrisiran), Alnylam Pharmaceuticals’ next-generation FAP therapy, may lower heart damage in people with FAP. The new analysis compared heart health between 122 Amvuttra-treated patients in a trial that supported the therapy’s approvals and 77 patients receiving a placebo in a separate trial. Particularly, Amvuttra was superior to a placebo at lowering blood levels of NT-proBNP, a marker of heart damage, and improving heart health and function as assessed by imaging scans. The therapy also reduced the formation of TTR clumps in the heart, particularly in patients with more severe heart disease at treatment’s start.
No. 1 – Onpattro effectively halts disease progression over long term
A real-world study in Italy demonstrated that Onpattro, Alnylam’s older FAP therapy, safely and effectively prevented disease progression for most people with early-stage FAP. For most of the 31 patients with available data after two years of treatment, neurological symptoms and ability to perform daily activities remained largely stable, while patients’ perceptions of neuropathy-related symptoms improved. During the third and fourth years of treatment, there was a worsening of neurological symptoms and disability scores, which was thought to be mainly driven by substantial worsening in two patients.
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At FAP News Today, we hope our reporting in 2024 was a source of useful information for everyone affected by FAP. We look forward to serving the FAP community in 2025, and wish all of our readers a very happy new year!
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