What clinical trials have been published for Lipoless and what were their main findings?

1. What trials have been published: the ALPACA Phase 2 randomized study reported in NEJM

The principal published trial is a multinational, randomized, controlled Phase 2 study of lepodisiran (ALPACA, ClinicalTrials.gov number NCT05565742) reported in the New England Journal of Medicine, which served as the basis for the late‑breaking session presentation at ACC.25 and multiple press summaries; that NEJM article provides the detailed efficacy and safety results ^{[1] [4]}.

2. Main efficacy findings: dramatic and durable Lp(a) suppression

Across the ALPACA Phase 2 population, a single 400‑mg dose of lepodisiran produced mean reductions in Lp(a) of roughly 94% from day 60 through day 180, with nearly comparable suppression observed out to 360 days and with repeat dosing at 180 days extending durability; multiple outlets summarized these near‑complete Lp(a) knockdowns as “nearly 90–94%” reductions sustained for many months after a single injection ^{[1] [2] [5]}.

3. Safety signals reported: no major immediate concerns, but limited follow‑up

Investigators reported no major safety concerns in the Phase 2 dataset presented; press and clinical summaries note tolerability consistent with the study population and no clear adverse events tied to very low Lp(a) levels in this trial, although authors and commentators emphasize that longer follow‑up and larger outcome studies are required to define the full safety profile ^{[2] [5] [3]}.

4. Context and caveats: surrogate biomarker versus clinical outcomes

The ALPACA results concern a biomarker—serum Lp(a) concentration—not hard cardiovascular endpoints; investigators and reviewers repeatedly underline that while large Lp(a) reductions are biologically promising, whether that translates into fewer heart attacks, strokes or deaths is unproven until phase 3 cardiovascular outcome trials report, and the community is watching ACCLAIM‑Lp(a) and other registration studies for those answers ^{[5] [3]}.

5. Conflicts, incentives and trial momentum: industry funding and rapid development

The lepodisiran program is funded by Eli Lilly, which stands to benefit commercially if outcomes are positive; reporting and expert statements disclose that funding and note investigator relationships, while several outlets and Cleveland Clinic commentary stress that phase 3 trials were launched quickly based on the early potency and durability data—an acceleration that both reflects enthusiasm and raises the stakes for rigorous outcome confirmation ^{[5] [3] [2]}.

6. What remains unanswered and why that matters

Published data establish that lepodisiran markedly and durably lowers Lp(a) in the short‑to‑medium term and appears tolerable in the trial population, but published sources do not yet provide evidence that these biomarker changes reduce clinical cardiovascular events or long‑term harms from very low Lp(a); therefore, definitive clinical benefit, optimal dosing intervals, population selection and rare safety signals remain open questions until phase 3 outcome data are available ^{[1] [5] [3]}.

7. Bottom line for readers following the “Lipoless” thread

If “Lipoless” refers to the Lp(a)‑lowering siRNA program published as lepodisiran, the clinical literature so far contains a high‑profile Phase 2 (ALPACA) publication showing potent, long‑lasting Lp(a) suppression and an acceptable short‑term safety profile, but it stops short of demonstrating clinical cardiovascular benefit—phase 3 trials funded and run by the developer are underway and will determine whether those biomarker gains translate into fewer heart attacks and strokes ^{[1] [5] [3]}.