Sanofi Acquires Rights to Arrowhead's Plozasiran for Hypertriglyceridemia in Greater China

Analysis reveals significant industry trends and economic implications

Release Date

2025-08-04

Category

Merger / Acquisition Event

Reference

Source

Breakthrough Clinical Results

Arrowhead Pharmaceuticals announced that its subsidiary, Visirna Therapeutics, has sold the rights to its investigational drug, plozasiran, for the treatment of hypertriglyceridemia in Greater China to Sanofi. Sanofi will pay $130 million upfront and up to $265 million in potential milestones. Plozasiran is a first-in-class RNA interference therapeutic designed to reduce the production of apolipoprotein C-III (APOC3). Visirna completed a Phase 3 clinical trial in Chinese patients with familial chylomicronemia syndrome (FCS), successfully meeting its primary and secondary endpoints, and has submitted a New Drug Application (NDA) to the NMPA in China. This deal highlights the growing importance of the Greater China market for pharmaceutical companies and the potential of plozasiran as a treatment for elevated triglycerides.

Key Highlights

  • Sanofi acquires rights to plozasiran in Greater China for $130 million upfront and up to $265 million in milestones.
  • Plozasiran successfully completed a Phase 3 clinical trial in China, meeting primary and secondary endpoints.
  • NDA for plozasiran submitted to the NMPA in China and received official acceptance.
  • Plozasiran has been granted Breakthrough Therapy Designation and Priority Review Designation by the China NMPA.

Incidence and Prevalence

Global Prevalence of Hypertriglyceridemia

Recent Global Estimates

The most recent data on hypertriglyceridemia (HTG) prevalence shows significant variation across different populations worldwide. A comprehensive 2020 cross-sectional study conducted in Primary Care with 6,588 adult subjects found that the crude HTG prevalence rates were 29.6% in the global population, with marked gender differences: 36.9% in men and 23.8% in women. When adjusted for sex and age, the prevalence rates were slightly lower at 27.0% globally, 34.6% in men, and 21.4% in women.

Another estimate from 2020 suggests that hypertriglyceridemia affects 15-20% of the adult population globally and is associated with overweight, metabolic syndrome, and diabetes mellitus.

Regional Variations

Regional studies show considerable differences in HTG prevalence:

  • A 2021 study in Saudi Arabia revealed a high prevalence of 43.4% among adults with high triglycerides (TG).
  • A 2020 study from Punjab, India reported an HTG prevalence of 21.6% (95% CI: 18.5-25.1).
  • In South Korea, a 2017 study with 15,932 non-diabetic participants found that 14.5% had persistent hypertriglyceridemia over a 2-year period.
  • In northern China (2015), hypertriglyceridemia was identified as one of twelve risk factors for hyperuricemia, which had a total prevalence of 13.7%.
  • Among rural Chinese women (2009), 39.2% of hypertensive women had hypertriglyceridemia.
  • In French Polynesia (1992), within a hyperuricemic population, 43% had high triglyceridemia.

Gender and Ethnic Differences

Gender disparities in triglyceride levels are consistently observed across studies. The 2020 cross-sectional study found that the arithmetic and geometric means of triglyceride levels were 120.5 and 104.2 mg/dL in the global population, 135.7 and 116.0 mg/dL in men, and 108.6 and 95.7 mg/dL in women.

Ethnic differences in hypertriglyceridemia prevalence have been documented: - Populations with Amerindian background show increased susceptibility to HTG. - Non-Hispanic blacks have lower triglyceride levels compared to non-Hispanic whites and Mexican Americans, despite having higher rates of type 2 diabetes mellitus and cardiovascular disease. - In the ELSA-Brasil study (2017), blacks showed a lower prevalence of high triglycerides compared to whites.

Risk Factors and Associations

The independent factors most strongly associated with HTG include: - Hypercholesterolemia (OR: 4.6) - Low HDL-C (OR: 4.1) - Hepatic steatosis (OR: 2.8) - Diabetes (OR: 2.0) - Obesity (OR: 1.9)

Persistent hypertriglyceridemia over time is associated with increased risk of developing conditions like diabetes mellitus.

In specific populations, such as patients with type 2 diabetes in Sweden (2014), pronounced hypertriglyceridemia (triglycerides >4.0 mmol/l) was observed in 3.4% of patients.

These findings highlight the significant global burden of hypertriglyceridemia with important variations across regions, ethnicities, and genders, emphasizing the need for targeted prevention and management strategies.

Drug used in other indications

Plozasiran Clinical Trials Beyond Hypertriglyceridemia

Beyond severe hypertriglyceridemia (SHTG), Plozasiran is being trialed for two other key indications:

Familial Chylomicronemia Syndrome (FCS)

Plozasiran, an APOC3-targeted small interfering-RNA drug, has already completed the pivotal Phase 3 trial for the treatment of familial chylomicronemia syndrome. This represents the most advanced clinical development stage for this therapeutic agent, though specific intervention details for this completed trial are not explicitly outlined in the available information.

Mixed Hyperlipidemia

A significant clinical trial for mixed hyperlipidemia has been conducted with the following intervention model:

  • Trial design: 48-week, phase 2b, double-blind, randomized, placebo-controlled trial
  • Randomization: Participants were assigned in a 3:1 ratio to receive plozasiran or placebo within each of four cohorts

  • Dosing cohorts:

  • First three cohorts: subcutaneous injection of plozasiran (10 mg, 25 mg, or 50 mg) or placebo on day 1 and at week 12 (quarterly doses)

  • Fourth cohort: 50 mg of plozasiran or placebo on day 1 and at week 24 (half-yearly dose)

  • Registration: The trial was registered on ClinicalTrials.gov (number NCT04998201)

Adolescent Population Studies

While not a separate indication, it's worth noting that model-based extrapolation suggests that the plozasiran dosing regimen of 25 mg every 3 months recommended for adult patients is likely safe and effective in adolescent patients aged 12 to 17 years old. This suggests potential expansion of existing indications to younger populations.

In summary, Plozasiran's clinical development program extends beyond hypertriglyceridemia to include familial chylomicronemia syndrome (completed Phase 3) and mixed hyperlipidemia (Phase 2b), with varying intervention models tailored to each indication and potential application in adolescent populations.

Arrowhead Pharmaceuticals' Approved Indications (2021-2024)

Based on a comprehensive review of available information, there is no data available regarding any regulatory approvals for Arrowhead Pharmaceuticals' therapeutic products during the period from 2021 to 2024.

The company specializes in developing RNA interference (RNAi) and small interfering RNA (siRNA) therapeutics, but no information indicates that any of their investigational products have received FDA approval or EMA approval within the specified timeframe.

Arrowhead Pharmaceuticals continues to work on developing treatments across various therapeutic areas, but as of the current information available, there are no approved drugs in their portfolio with specific indications that have received regulatory clearance in the last three years.

The pharmaceutical landscape includes numerous other companies with approved medications for various conditions, but Arrowhead Pharmaceuticals specifically does not appear to have successfully brought any of their candidates through the complete regulatory approval process during this period.

For patients and healthcare providers interested in RNAi therapeutics, it's worth noting that while Arrowhead has an active development pipeline, no treatments have yet achieved the milestone of regulatory authorization for clinical use in any therapeutic indications within the timeframe of 2021-2024.