Merck's peptide story is anchored by enlicitide (LIPFENDRA), a macrocyclic peptide oral PCSK9 inhibitor FDA-approved July 16, 2026 as the first once-daily oral PCSK9 inhibitor for adults with hypercholesterolemia (including heterozygous familial hypercholesterolemia). The Phase 3 CORALreef program delivered 56-59% placebo-adjusted LDL-C reductions across CORALreef Lipids and CORALreef HeFH, matching injectable PCSK9 monoclonal antibodies. Merck priced the tablet at $315 per month, roughly one-third the injectable class. The molecule is also notable for its manufacturing chemistry: the May 7, 2026 Science paper from the Merck process group described an engineered-enzyme biocatalytic cascade that cuts synthesis step count by more than half.
The broader peptide footprint includes the April 2025 Cyprumed deal worth up to $493M in milestones for oral peptide delivery platform access, the longstanding peptide-drug-conjugate research program, and a Q1 2026 Keytruda revenue baseline of $7.9B — recently overtaken by Eli Lilly's Mounjaro ($8.66B) as the world's top-selling drug per Bloomberg May 6. Merck's Q1 oncology cycle also included new ASCO-GU bladder and kidney cancer data plus continued peptide-radioligand work.
Stories here cover trial readouts, partnership economics, and the broader macrocyclic strategy. See #enlicitide, #pcsk9, and #keytruda.
The US Food and Drug Administration approved Merck's LIPFENDRA (enlicitide) 20 mg tablets Thursday July 16, 2026 as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in adults with hypercholesterolemia, including heterozygous familial hypercholesterolemia (HeFH). LIPFENDRA is a novel macrocyclic peptide and becomes the first FDA-approved oral PCSK9 inhibitor. In the registrational Phase 3 CORALreef Lipids trial, enlicitide achieved a 56% placebo-adjusted LDL-C reduction; in CORALreef HeFH the reduction was 59%. Every other FDA-approved PCSK9 inhibitor (Amgen's Repatha/evolocumab, Regeneron/Sanofi's Praluent/alirocumab) is delivered by subcutaneous injection every two to four weeks; enlicitide is the first approved as a once-daily oral tablet. Merck priced LIPFENDRA at $315 per month list price, roughly one-third the approximately $700-900/month list prices of the injectable PCSK9 antibodies. The approval extends the macrocyclic peptide platform's clinical validation and opens a new oral chapter for a drug class that had been injectable-only since the first FDA approvals in 2015.
The House Select Committee on the Chinese Communist Party's July 17, 2026 response deadline arrives tomorrow for five drugmakers on records of clinical trials conducted at Xinjiang-region hospitals and Chinese military medical centers: Merck, AbbVie, Eli Lilly, Pfizer, and Bristol-Myers Squibb. Chair Rep. John Moolenaar (R-Michigan) sent letters on June 29 requesting due diligence, data protection processes, and standards at Chinese trial sites. Updated trial counts documented in the letters: Merck sponsored or collaborated on 224 clinical studies in China since 2005, including at least 31 trials involving Xinjiang-region hospitals and at least 40 trials involving Chinese military medical centers. Eli Lilly appears to have sponsored or collaborated on more than 220 clinical studies in China since 2003, with at least 11 Xinjiang-region trials and at least 16 military-medical-center trials between 2016 and 2024. Pfizer had at least 6 Xinjiang-region trials and 43 military-hospital trials. AbbVie had 17 Xinjiang and 16 military. Bristol-Myers Squibb's specific counts were not detailed in the summary but the company received the same request. Merck stated that patient safety and ethical integrity are foundational to its clinical research; Eli Lilly said it is reviewing the letter closely.
The House Select Committee on the Chinese Communist Party (chaired by Rep. John Moolenaar, R-Michigan) faces its July 17 response deadline one week from tomorrow for five drugmakers under national-security investigation over clinical trials conducted at Chinese sites: Eli Lilly, Merck, AbbVie, Pfizer, and Bristol-Myers Squibb. The letters, first reported by Reuters, were dated June 29 and asked companies to provide details of due diligence, data protection processes, and other standards at their trial sites in China, with particular attention to the Xinjiang region and military hospitals. Eli Lilly disclosed sponsoring at least 11 trials at Xinjiang-region hospitals plus at least 16 trials at Chinese military medical centers and hospitals, across type 2 diabetes, heart disease, obesity, Alzheimer's disease, axial spondyloarthritis, breast cancer, lupus, alopecia, Crohn's disease, and additional indications. The committee said it has no evidence of company wrongdoing but cites potential ethical and national-security risks. The letters run parallel to the BIOSECURE Act framework, the June 30 STAT Pharmalittle preview of the probe, and industry warnings from Fierce Biotech that the scrutiny risks 'huge distraction and expense' for US biopharma.
A Chemical & Engineering News feature published in June 2026, drawing on data from the CAS Content Collection, documented the cyclic-peptide patenting surge over 2020 to April 2026. Chinese universities are the top filers globally on cyclic peptides. Outside China, US universities lead. Among corporates, Bicycle Therapeutics and Bristol Myers Squibb were called out for sustained patent activity covering cancer, infectious, inflammatory, and autoimmune disease indications. The article frames cyclic peptides as bridging the small-molecule and biologic divide: enhanced conformational rigidity, elimination of unstable terminal residues, and improved metabolic stability are the structural advantages that allow some cyclic peptides to be dosed orally. Merck's enlicitide decanoate (MK-0616, oral PCSK9 macrocyclic peptide for hyperlipidemia) was cited as the proof point for oral-pill cyclic-peptide drug development; an enlicitide NDA submission was underway as of mid-2026. The broader market backdrop: macrocyclic and stapled peptides are projected to grow from $1.22 billion in 2024 to $4.76 billion by 2030 at a 21.44% CAGR, driven mostly by oncology pipelines and the macrocyclic deal flow that includes the Unnatural Products-Novartis $1.7-1.8B cardiovascular pact (February 2026), Biogen-Dayra $50M+ immunology pact (November 2025), and the Parabilis Helicon platform (Regeneron $2.3B collaboration, June 10 $670M record IPO).
ASCO 2026 abstracts will release on asco.org/abstracts beginning 5:00 PM ET on Wednesday May 21, ahead of the May 29-June 2 Chicago meeting. The peptide-oncology slate is substantial: Pfizer announced 40+ company-sponsored, investigator-sponsored, and collaborative oncology abstracts including three late-breaking sessions; Bicycle Therapeutics has an oral and four poster presentations on zelenectide pevedotin (BT8009, nectin-4 PDC) with Duravelo-2 interim data; Avacta has Phase Ia/Ib data on AVA6000 (FAP-Dox PDC) in salivary gland cancers; BioVaxys's MVP-S survivin peptide vaccine PESCO trial data; BriaCell's six Bria-IMT/Bria-OTS+ presentations on metastatic breast cancer; and Replimune's RP1 + nivolumab 3-year melanoma OS data. Crinetics CRN09682 SSTR2 NDC BRAVESST2 update expected.
Bloomberg reported May 6 that Eli Lilly's Mounjaro displaced Merck's Keytruda as the world's best-selling pharmaceutical in Q1 2026 — $8.66B Mounjaro Q1 sales vs Keytruda's $7.9B Q1 sales. The Mounjaro+Zepbound combined tirzepatide platform generated $36.5B in 2025, outpacing Keytruda's $31.6B. Keytruda had held the #1 ranking since Q1 2023, when it displaced AbbVie's Humira. The shift is the first time a peptide therapeutic has taken the top spot since the historical run of insulin biosimilars. The narrative also frames Lilly's $4.5B Lebanon Indiana manufacturing recommitment and the broader $21B Indiana capital plan as the supply-chain answer to demand at that scale.
Joelle Pelletier's perspective in Science (volume 392, pages 582-583, published online May 8) accompanies the Merck enlicitide biocatalytic synthesis paper and frames the enzyme-cascade route — engineered enzymes plus chromatography-free crystallization to cut step count by more than half — as a template that goes well beyond enlicitide. The piece argues that the limiting step for oral macrocyclic peptide therapeutics has been the manufacturing cost of multi-step protected-residue chemistry, not pharmacology or pharmacokinetics; biocatalysis collapses the cost curve and unlocks a pipeline of oral peptides at large molecular weights that have been quietly stuck in preclinical or Phase 1 economics. The framing matters as enlicitide (oral PCSK9 inhibitor with 57% LDL-C reduction at 24 weeks) heads toward NDA filing.
Merck scientists published in Science a convergent biocatalytic synthesis of enlicitide decanoate, an investigational oral PCSK9 inhibitor and macrocyclic peptide. A tailored suite of engineered enzymes catalyzes selective peptide fragment formation, coupling, and macrocyclization in a protecting-group-free sequence; combined with chromatography-free crystallizations, the route reduces step count by more than half versus prior state-of-the-art methods. Enlicitide is in Phase 3 (CORALreef, with –55.8% LDL-C reported earlier in 2026) and would be the first oral PCSK9 inhibitor if approved. The paper matters beyond enlicitide: protein-engineering-led cascades shift the cost basis for any large macrocyclic peptide program facing peptide-CDMO bottlenecks.
Merck's investigational oral macrocyclic peptide PCSK9 inhibitor demonstrated significantly greater LDL-C reductions at 8 weeks vs guideline-recommended oral non-statin therapies, delivering injectable-level cholesterol lowering in pill form.