Merck's Oral PCSK9 Inhibitor Shows Promise in Phase III Trials, Positioning Company as Leader in Cholesterol Treatment Race

Merck & Co. has taken a significant step forward in its bid to bring the first oral PCSK9 inhibitor to market, with its experimental drug enlicitide decanoate showing positive results in two Phase III trials. The studies, part of the company's CORALreef program, demonstrated the drug's ability to significantly lower low-density lipoprotein cholesterol (LDL-C) in patients with high cholesterol, potentially unlocking a multi-billion dollar opportunity for the pharmaceutical giant.

Phase III Trial Results and Drug Mechanism

The CORALreef HeFH study enrolled adults with heterozygous familial hypercholesterolemia (HeFH), while the CORALreef AddOn trial focused on patients with hypercholesterolemia. Both studies included participants with a history of or at risk for atherosclerotic cardiovascular disease who were also being managed with statins.

Merck reported that treatment with enlicitide decanoate resulted in "statistically significant and clinically meaningful reductions" in LDL-C compared to placebo and other oral non-statin agents such as ezetimibe and bempedoic acid. The drug also met all key secondary endpoints in both studies.

Enlicitide decanoate works by inhibiting the PCSK9 protein, which regulates the uptake of cholesterol into cells. By blocking this protein, the drug allows cells to remove more LDL-C from the blood, effectively lowering cholesterol levels.

Market Implications and Competition

If approved, enlicitide decanoate would become the first oral PCSK9 inhibitor on the market, potentially offering a more convenient alternative to existing injectable PCSK9 inhibitors like Amgen's Repatha and Sanofi-Regeneron's Praluent. This could give Merck a significant advantage in the hypercholesterolemia market, which has seen challenges in the adoption of injectable therapies.

Merck's CEO Robert Davis has expressed confidence in the drug's potential, stating that the company's investment in production could allow for competitive pricing, potentially avoiding the reimbursement issues that have hindered sales of injectable PCSK9 inhibitors.

However, Merck is not alone in the race to develop an oral PCSK9 inhibitor. AstraZeneca is also developing a PCSK9 pill, which some analysts believe could pose a significant threat to Merck's program. The competition between these two pharmaceutical giants is likely to intensify as they move closer to potential market approval.

Future Outlook and Ongoing Studies

While the initial results are promising, Merck has not yet provided specific data from the trials. The company is continuing its extensive CORALreef development program, which includes two additional late-stage trials: CORALreef Lipids and CORALreef Outcomes. The Lipids study is expected to conclude later this year, while the Outcomes trial has a primary completion date of November 2029.

The success of enlicitide decanoate is crucial for Merck's future growth strategy, particularly as the company faces the approaching patent expiration of its blockbuster cancer immunotherapy, Keytruda. The potential of enlicitide to become a multi-billion dollar product has captured the attention of investors and analysts, with BMO Capital Markets describing it as a "multi-billion dollar opportunity expanding the PCSK9 market beyond current injectable therapies."

As Merck moves forward with its development of enlicitide decanoate, the pharmaceutical industry will be watching closely to see if this oral PCSK9 inhibitor can indeed revolutionize cholesterol treatment and capture a significant share of the market.