Merck Enters Competitive Lp(a) Race with $2B Deal for Chinese Biotech's Oral Drug

Merck & Co. has made a significant move in the cardiovascular drug market, announcing a licensing deal with China-based Jiangsu Hengrui Pharmaceuticals for an oral lipoprotein(a) [Lp(a)] inhibitor. The agreement, valued at up to $1.97 billion, puts Merck in direct competition with several pharmaceutical giants in the race to develop novel treatments targeting Lp(a), a protein particle associated with increased risk of cardiovascular disease.

Deal Details and Strategic Implications

Merck will pay $200 million upfront to Jiangsu Hengrui for the rights to HRS-5346, an investigational small-molecule Lp(a) inhibitor, outside of the Greater China region. The deal includes potential additional payments of up to $1.77 billion tied to developmental, regulatory, and commercial milestones, as well as royalties on net sales if the drug receives regulatory approval.

This partnership aligns with a growing industry trend of major pharmaceutical companies looking to Chinese biotechs for innovative therapies. Dean Li, president of Merck Research Laboratories, stated that HRS-5346 represents "an important addition that expands and complements our cardio-metabolic pipeline."

The Lp(a) Landscape: A Competitive Field

The Lp(a) inhibitor market has become increasingly competitive, with several pharmaceutical companies developing therapies targeting this protein:

• Novartis is leading the pack with an RNA-based medicine in Phase 3 testing, with cardiovascular outcomes data expected in 2026.
• Amgen is also working on an oligonucleotide therapy to stop Lp(a) production.
• Eli Lilly's oral candidate, muvalaplin, has completed Phase 2 trials, showing an 81.7% decrease in Lp(a) levels versus placebo at the 60-mg dose.
• AstraZeneca recently partnered with CSPC Pharmaceutical Group for an oral Lp(a) disruptor, YS2302018, currently in preclinical testing.

Merck's entry into this field with an oral small-molecule inhibitor could potentially address a significant market need. Approximately 1.4 billion people worldwide have elevated Lp(a) levels, making it an attractive target for pharmaceutical intervention.

Clinical Development and Market Potential

HRS-5346 is currently undergoing a Phase 2 trial in Beijing, expected to conclude by the end of the year. The study is recruiting volunteers with heart disease or at high risk of developing it, testing three doses against a placebo to evaluate Lp(a) reduction over 12 weeks.

While early data from injectable RNA therapies have shown impressive results, with greater than 90% reduction in Lp(a) levels, oral medications like HRS-5346 could potentially compete in two key market segments:

1. Patients with very high Lp(a) levels (10-15% of the population) who might prefer an oral option over injectables.
2. The "vast majority" of people with moderately elevated Lp(a) levels who may not qualify for injectable therapies.

Jefferies analyst Dennis Ding noted that "the Lp(a) market is very large and we consider this as pharma white space given [there are] no approved therapies."

As the pharmaceutical industry continues to invest heavily in Lp(a) inhibitors, Merck's latest deal underscores the potential of this emerging therapeutic area and the ongoing shift towards oral treatments for cardiovascular risk factors.