Statins are a standard drug for managing high cholesterol, but for patients who need something stronger, a newer class of medicines has become another option. In the more than a decade since these PCSK9 inhibitors have reached the market, all of them have been injectable. FDA approval of a Merck drug brings patients the first oral option in the class.
The Thursday regulatory decision covers use of the new Merck drug alongside diet and exercise as a way to reduce excessively high LDL-cholesterol, including an inherited form of high cholesterol called heterozygous familial hypercholesterolemia (HeFH). Known in development as enlicitide, Merck’s once-daily pill will be marketed under the brand name Lipfendra.
PCSK9 is a protein produced by the liver. High levels of this protein reduce the organ’s ability to clear LDL-cholesterol from the blood. The first PCSK9 inhibitors, Amgen’s Repatha and Regeneron Pharmaceuticals’ Praluent, were approved in 2015. These antibody drugs are administered as injections every two or four weeks. The FDA’s 2021 approval of Novartis drug Leqvio brought patients a twice-a-year injectable drug that uses small-interfering RNA to break down the messenger RNA for PCSK9, reducing levels of the protein. Eli Lilly is in clinical testing with a potential one-time treatment, a gene therapy that permanently turns off the gene that codes for PCSK9.
Lipfendra is a different kind of PCSK9 inhibitor. While peptide drugs are typically administered as injections, the Merck drug is a macrocyclic peptide — the amino acids that make up the peptide are formed into a ring shape that enables it to be made into a pill. This drug emerged from a research collaboration with Ra Pharmaceuticals (acquired by UCB in 2020) that began in 2013.
In two placebo-controlled Phase 3 clinical trials, one in patients with hypercholesterolemia and the other in patients with HeFH, Lipfendra led to statistically significant reductions in LDL cholesterol. In the hypercholesterolemia study, the safety profile was similar to placebo. In the HeFH trial, the most common adverse reactions were diarrhea and dizziness.
“By harnessing the innovative science of PCSK9 inhibitors and novel macrocyclic peptide technology, Lipfendra was designed to significantly lower LDL-C in the form of a convenient once-daily pill,” Dean Li, president, Merck Research Laboratories, said in a prepared statement.
Lipfendra must be taken on an empty stomach and then patients must refrain from eating for another 30 minutes. That’s consistent with restrictions for other oral peptides, such as the pill formulation of Novo Nordisk’s Wegovy and Icotyde, a Johnson & Johnson plaque psoriasis pill approved in March. Lipfendra joins a Merck cardiometabolic and respiratory portfolio led by Winrevair, a blockbuster drug approved for treating pulmonary arterial hypertension. Analysts expect Lipfendra will become a blockbuster seller as well.
Last December, the FDA awarded Lipfendra a Commissioner’s National Priority Review Voucher, part of a pilot program that accelerates the review of medicines in the national interest. A Merck spokesperson confirmed by email that the voucher was applied to the new cholesterol drug. The company also said it will make the pill available through TrumpRx, a website that lists prices of certain drugs from companies that have agreed to “most-favored nation” pricing, in which the U.S. price of a drug matches the lowest price of the same drug in a comparable nation.
Merck’s list price for Lipfendra is $315 for a 30-day supply. By comparison, a 30-day supply of Lipitor, a popular oral statin that has been off-patent for years, costs an average $58.05, according to GoodRx. Merck said it expects Lipfendra will become available in coming weeks.
There are plenty of other drug approvals in the news. Here’s a recap of recent regulatory developments:
Cancer Drug Approvals
—FDA approval of Orca Bio’s Tregzi makes the cell therapy the first one for blood cancers based on regulatory T cells (Tregs), a type of immune cell. This allogeneic therapy, made by isolating Tregs from a matched donor, was developed to reduce the risk of graft-versus-host disease, a common complication of the hematopoietic stem cell transplants that are a standard treatment for certain blood cancers.
—The Gilead Sciences’ Trodelvy expanded its label to include the first-line treatment of triple-negative breast cancer. This antibody drug conjugate was initially approved in 2020 as a third-line treatment for this type of cancer. In the first-line setting, Trodelvy will compete against the AstraZeneca and Daiichi Sankyo ADC Datroway, which won its FDA approval in this indication in May.
—The European Commission approved Amgen’s Imdylltra as a second-line treatment for extensive-stage small cell lung cancer. This antibody drug won FDA approval in 2024 and is marketed in the U.S. as Imdelltra.
—The Merck immunotherapy Keytruda expanded its approval to include its use in combination with Astellas Pharma’s Padcev for patients with muscle invasive bladder cancer. Specifically, the new decision covers treatment before and after cystectomy, which is surgery to remove the bladder. The combination was previously approved only patients who are ineligible for chemotherapy. Now all patients who are candidates for cystectomy are eligible for Keytruda and Padcev.
Approvals in Autoimmune Disease
—Novartis drug Fabhalta converted its accelerated FDA approval to a traditional one as a treatment for immunoglobulin A nephropathy, a disorder affecting the kidneys. The complement inhibitor’s accelerated approval in 2024 was based on clinical data showing reduction in urine proteins indicative of disease. The full approval is based on Phase 3 data showing statistically significant and clinically meaningful improvement in estimated glomerular filtration rate, a measure of kidney function.
—Vera Therapeutics received accelerated FDA approval for Trutakna for the treatment immunoglobulin A nephropathy, a disorder that affects the kidneys. While there are other FDA-approved therapies for this rare disease, Trutakna is the first approved therapy that works by blocking two particular proteins, APRIL and BAFF. This drug also has potential applications in other autoimmune diseases; Vera projects the market opportunity could top $10 billion.
—Viridian Therapeutics’ Lumvoa landed FDA approval for treating both the chronic and active phases of thyroid eye disease, an autoimmune disorder that leads to inflammation around the eyes. This antibody drug will compete against the blockbuster Amgen drug Tepezza with the advantage of a shorter dosing regimen.
—Sanofi’s Tzield expanded its FDA approval to include the treatment of stage 3 type 1 diabetes in children age 8 and older. This decision is an accelerated approval that requires the drugmaker to provide additional data. Tzield was first approved in 2022 for delaying the progression of type 1 diabetes in adults. In April, that approval was expanded to children as young as age 1.
Cardiometabolic Drug Approvals
—Ionis Pharmaceuticals’ Tryngolza is now the first FDA-approved first treatment for severe hypertriglyceridemia (sHTG), a metabolic disorder that leads to dangerously high blood levels of triglycerides that spark a range of cardiometabolic complications. This drug is a key part of Ionis’s strategy to commercialize drugs on its own rather than working through partners.
—The European Commission approved the oral version of the Novo Nordisk obesity drug, Wegovy. The agency also approved a 7.2 mg dose of the injectable Wegovy, introducing a higher dosing option for those who need it. The FDA approved Wegovy pill late last year.
—The commission granted marketing authorization to Arrowhead Pharmaceuticals’ Redemplo as a treatment for familial chylomicronemia syndrome (FCS). This rare genetic disease leads to dangerously high blood levels of triglycerides, a type of fat. The FDA approved Redemplo, a small-interfering RNA drug, last November.
—AbbVie oral migraine drug Aquipta received Commission approval for treating acute migraine in adults. The CGRP antagonist was approved by the FDA in 2021 and is marketed in the U.S. as Qulipta.
Other Drug Approvals
—The GSK and Spero Therapeutics oral antibiotic tebipenem pivoxil received FDA approval for treating complicated urinary tract infections in adults who have limited or no alternative oral treatment options. GSK, which licensed rights to most of the global rights to the product, will market it under the brand name Utebzi. The regulatory decision was based on Phase 3 results showing oral Utebzi was non-inferior to an intravenous antibiotic.
—Gilead Sciences’ bulevirtide is now the first approved treatment for hepatitis delta viral infection in the U.S. The FDA awarded accelerated approval to the antiviral drug, which will be marketed as Hepcludex. The drug works by binding to a particular receptor on liver cells, preventing the virus from attaching to it.
Regulatory Moves
—Health and Human Services Secretary Robert F. Kennedy Jr. ended the emergency use authorizations granted for drugs and medical devices during the Covid-19 pandemic. The department said that the circumstances that justified the authorizations no longer exist. The terminations for medical devices will take effect 180 days after the Secretary Kennedy’s determination. For drugs and biological products, the termination takes effect in 12 months.
—The European Medicines Agency recommended revoking approval for Tavneos, an Amgen drug marketed in Europe by CSL Vifor as a treatment for ANCA-associated vasculitis, an inflammatory disorder affecting blood vessels and organs. The agency cited liver toxicity risks and alleged manipulation of the clinical trial for Tavneos’s pivotal study, the same reasoning raised in the FDA’s proposal to withdraw the drug from the U.S. market.
—The FDA reversed its position recommending uniQure’s Huntington’s disease gene therapy undergo a double-blind study with a sham control. The agency said the existing clinical data, which used a historical control, could suffice. UniQure said it plans to seek accelerated FDA approval and will work with the agency on the design of a confirmatory study.
Same Drug, Easier Dosing
—Patients can now start treatment with Alzheimer’s drug Leqembi at home. The FDA approved Eisai and Biogen product Leqembi Iqlik for use as the starting dose. Iqlik is a self-injection device for administering the injectable formulation of Leqembi, which was initially developed and approved as an intravenous infusion given every two weeks. The new regulatory decision expands on the 2025 approval of Leqembi Iqlik, which permitted only maintenance dosing and required patients to start treatment with the IV-infused formulation.
—Sarclisa, a Sanofi multiple myeloma drug that first reached patients as an intravenous infusion, is now approved in a more convenient injectable formulation. It’s the first FDA approval for a drug administered by a wearable, on-body auto-injection device.
—The FDA approved Besremi Pen, a device that administers PharmaEssentia’s drug for polycythemia vera drug. This self-injection device should offer easier administration compared to pre-filled syringes that the company had since Besremi’s FDA approval in 2021.
Complete Response Letters
—Companies that recently received FDA complete response letters (CRLs) for manufacturing issues include Unicycive Therapeutics for hyperphosphatemia drug oxylanthanum carbonate; Sobi for the gout drug NASP; and Cingulate for it attention deficit hyperactivity disorder drug CTx-1301. The letters did not raise any safety or efficacy concerns about these drug candidates.
—The CRL sent to Tris Pharma did raise questions about safety and efficacy. The company’s application sought approval for its extended-release oral suspension oxybate for narcolepsy. The FDA letter said the scientific bridge between Tris’s drug and the already approved oxybates, Xyrem and Xywav, is inadequate. The agency added that more clinical data are needed to support the safety and efficacy of the Tris drug.
Photo: Stuart Ritchie, Getty Images
