IONIS PHARMACEUTICALS, INC.

The global Multiple System Atrophy (MSA) market is experiencing significant growth driven by emerging alpha-synuclein targeting therapies and advanced diagnostic technologies including high-resolution MRI and biomarker identification.

Alnylam's RNAi drug vutrisiran demonstrated a 28% reduction in all-cause mortality and recurrent cardiovascular events in ATTR cardiomyopathy patients, with efficacy increasing to 33% in patients not taking Pfizer's tafamidis.

uniQure secured FDA agreement to pursue accelerated approval for its Huntington's disease gene therapy, potentially expediting treatment availability.

• The FDA has approved BridgeBio Pharma's Attruby (acoramidis) for transthyretin amyloidosis cardiomyopathy (ATTR-CM), a heart condition leading to heart failure and death. • Attruby demonstrated a 42% reduction in composite all-cause mortality and recurrent cardiovascular-related hospitalizations compared to placebo in the ATTRibute-CM trial. • BridgeBio is launching Attruby at a list price of $18,759 for a 28-day supply, positioning it to compete with Pfizer's Vyndamax, which dominates the ATTR-CM market. • Several other companies, including Alnylam and AstraZeneca/Ionis, are also developing therapies for ATTR, potentially disrupting the current treatment landscape.

• A subgroup analysis from the FOREST-HCM trial revealed that aficamten could reduce the need for septal reduction therapy (SRT) in obstructive hypertrophic cardiomyopathy (oHCM) patients. • After 24 weeks of aficamten treatment, approximately 70% of SRT-eligible patients were no longer considered eligible for the procedure. • The study also demonstrated improvements in NYHA functional class, with a significant proportion of SRT-eligible patients experiencing at least a one-class improvement. • Aficamten demonstrated greater improvements in SRT-eligible patients relative to those in the remaining cohort (21.7 [SD, 19.3] vs 13.5 [SD, 13.9]; P = .003).

• BridgeBio's acoramidis, a TTR stabilizer, awaits FDA approval and could compete with Pfizer's tafamidis in the $5.2 billion ATTR-CM market. • Clinical trial data shows acoramidis achieving an 81% survival rate and halving cardiovascular-related hospitalizations, though all-cause mortality benefit is debated. • Emerging RNA therapies from Alnylam and AstraZeneca/Ionis, along with Intellia's gene editing approach, may further intensify competition in the ATTR-CM treatment landscape.

Muvalaplin, an oral drug by Eli Lilly, significantly reduced lipoprotein(a) (Lp(a)) levels in a Phase 2 trial, offering a potential non-injectable treatment option.

The FDA has accepted a new drug application for donidalorsen, an RNA-targeting drug, for prophylactic treatment of hereditary angioedema (HAE) in patients 12 years and older.

Immunic's phase 3 ENSURE program, evaluating vidofludimus calcium for relapsing multiple sclerosis (RMS), will continue as planned after a positive IDMC review.

The Committee for Medicinal Products for Human Use (CHMP) has recommended Wainzua (eplontersen) for approval in the EU to treat hATTR-PN.