ATTRv amyloidosis: 2026 so far

Evidence shifted from short-term stability to multi-year follow-up.

In the months covered, newer follow-up and extension data added more long-term context. Gene-silencing therapies were repeatedly linked with sustained lowering of blood TTR and neuropathy and function measures that were often stable or worsened more slowly over months to years. Early 2026 reports highlighted that TTR suppression in routine care was consistent, but follow-up was short and results more often showed stability than clear improvement. Later reports added multi-year extension data and longer real-world follow-up. These showed stability for many people, but progression was still seen in some datasets. Several eplontersen analyses were described as exploratory/post hoc (extra analyses done after the main plan) and often used historical placebo comparisons (older placebo data used as a reference), which supported stabilization signals but left uncertainty about direct drug-to-drug comparisons. This means you can usually expect TTR lowering to be reliable in the near term, while symptom and function changes more often look like slowing or stability rather than reversal, and clear head-to-head superiority between specific silencers is still not proven.

Research covered in: February 2026, March 2026, April 2026, May 2026, June 2026, September 2026

More real-world switch/add-on reports appeared as 2026 progressed.

In January to September 2026, several real-world reports described what happened when people worsened on tafamidis and then switched to, or added, an RNA-silencing therapy (a treatment that lowers TTR by turning down its production). These reports most often described stability afterward, and sometimes slower neuropathy worsening. Early in 2026, a French retrospective cardiomyopathy cohort (a look back at medical records in people with heart involvement) reported that a notable minority worsened during tafamidis-only periods. After switching/adding patisiran or vutrisiran, most were stable and none were reported to worsen. Later, a Val30Met cohort reported slower worsening on a neuropathy impairment score after switching from tafamidis to patisiran following progression. A separate transplant-exposed group (domino liver transplant recipients who later developed ATTR amyloid) also included a small number who progressed on tafamidis and appeared to stabilize after switching to an siRNA therapy (a small interfering RNA gene-silencing medicine). These reports can help set expectations for what treatment changes may look like in routine care, but they are limited by being retrospective, including mixed phenotypes, and not having head-to-head randomized comparisons.

Research covered in: January 2026, February 2026, May 2026, September 2026

Routine-care comparisons highlighted tolerability and neuropathy-score differences.

In the months covered, one multicenter routine-care comparison reported differences between patisiran and inotersen. People treated with patisiran more often had stable or improved neuropathy exam scores and slower worsening on a neuropathy impairment score than those treated with inotersen. In the same dataset, stopping treatment because of side effects was reported much more often with inotersen, and it was not seen with patisiran in that group. The report also described an early, retrospective signal that a sweat/skin conductance measure (a test of how skin conducts electricity, linked to sweating) might help predict response. Because this was an observational comparison (not a randomized trial), it cannot fully separate medication effects from differences in who received each drug or from differences in follow-up. In practical terms, treatment experiences in routine care may differ for both symptom trajectory and tolerability, but this evidence does not prove a definitive ranking without direct head-to-head trials.

Research covered in: July 2026

Focus moved from exploratory PN analyses to CM trial readiness.

Across January to September 2026, eplontersen reports expanded in scope. They ranged from exploratory/post hoc analyses in ATTRv polyneuropathy (ATTRv-PN; nerve damage from hereditary ATTR) to pharmacology work (how the drug behaves in the body) and a baseline description of a large ATTR cardiomyopathy trial population. Subgroup analyses in ATTRv-PN reported large TTR reductions and generally maintained neuropathy and quality-of-life measures across genetic groups and across sex. These included an exploratory subgroup with cardiomyopathy, and they relied on smaller subgroups and historical placebo comparisons. Later reports added an integrated pharmacology analysis supporting substantial steady-state TTR lowering with monthly dosing. They also described baseline characteristics of the ongoing CARDIO-TTRansform trial (including many participants already on contemporary background care), without reporting clinical outcomes. As a result, the reports available so far give clearer information about how consistently TTR is lowered and who is being studied in cardiomyopathy, while symptom and outcome benefits in ATTR-CM are still not answered in these updates.

Research covered in: March 2026, April 2026, May 2026, August 2026, September 2026

Consensus and case reports repeatedly underscored CNS/eye unmet need.

In the months covered, consensus documents and case-based evidence repeatedly stated that current approved disease-modifying therapies are not expected to meaningfully stabilize central nervous system (CNS) involvement (brain and spinal cord), and that eye and brain manifestations remain a major unmet need. Case reports supported this concern by describing ongoing or progressive leptomeningeal/CNS disease (leptomeningeal disease; amyloid affecting the membranes around the brain/spinal cord) despite treatment. This included a long follow-up case on a CNS-penetrant stabilizer (a stabilizer designed to reach the CNS). Observational work also described brain-related episodes in long-standing V30M disease and MRI (magnetic resonance imaging; detailed pictures of the brain) findings that varied by cohort and subtype. These reports did not measure how often CNS/eye disease progresses under different therapies, but they consistently framed CNS/eye involvement as an area where standard options may not have the same impact as they do for peripheral nerve or heart disease. This can mean a different monitoring plan and different expectations when symptoms involve the brain or eyes, and it helps explain why these manifestations remain a focus of research in the reports available.

Research covered in: July 2026, August 2026, September 2026