March 2026

PDR Drug Update 

Integrating PCSK9 Inhibitors into LDL-C-Lowering Therapy

Hypercholesterolemia, a common type of hyperlipidemia, is characterized by elevated low-density lipoprotein cholesterol (LDL-C). Approximately one-third of adults in the US have high-LDL-C, which is a primary risk factor for atherosclerotic cardiovascular disease (ASCVD). Contemporary lipid-lowering guidelines emphasize lifestyle optimization, use of statins, and an expanding portfolio of non-statin therapies to achieve substantial LDL-C reduction. Treatment approaches are stratified by risk and designed to attain specific goals for lowering LDL-C. The objectives are especially aggressive for patients at high risk, such as those with heterozygous familial hypercholesterolemia.

Individuals with familial hypercholesterolemia (FH) are born with high LDL-C. It occurs due to a defect inherited from either one or both parents and involves mutations in genes that affect how LDL is used or removed from the body. One in every 200 adults has a FH genetic mutation, but many are unaware of it since physical symptoms may not be apparent. Homozygous FH (HoFH) is rarer because it requires inheritance from both parents. Heterozygous FH (HeFH) is more common. Regardless of type, FH results in lifelong elevated LDL-C and without intervention, individuals with the condition face drastically heightened risk for ASCVD. For high-risk patients, the goal is to lower LDL-C as much as possible for as long as possible to achieve the greatest benefit. Sustained LDL-C lowering has been shown to reduce the incidence of myocardial infarction, stroke, and cardiovascular mortality.

Clinical guidelines consistently advocate for early and drastic LDL-C reduction. Typically, combination therapy is necessary in order to achieve and maintain health goals. First-line treatment for LDL-C-lowering will almost always involve statins. For patients with FH, aggressive health targets are recommended, and additional pharmacotherapy beyond high-intensity statin therapy is common. To achieve the lower targets suggested in more recent hypercholesterolemia management guidelines, prescribers may use several add-on therapies that help significantly reduce LDL-C levels. In certain circumstances, ezetimibe may be added to existing statin therapy. In patients at very high risk, such as those with HeFH, the addition of PCSK9 inhibitors may be feasible, as they are more potent than statins and, when combined with them, can dramatically lower LDL-C levels.

PCSK9 inhibitors are particularly effective because they preserve LDL receptors, driving large reductions in LDL-C beyond what statin and ezetimibe therapies alone can typically achieve. Clinical trial results have historically demonstrated substantial LDL-C reductions and successful attainment of LDL-C targets in HeFH patients treated with these agents. The most recent approval for a PCSK9 inhibitor was for Lerochol (lerodalcibep-liga), a third-generation recombinant fusion protein. The therapy is approved for subcutaneous use as an adjunct to diet and exercise to reduce LDL-C in adults with hypercholesterolemia, including HeFH.

Approval for Lerochol was based on data from the phase 3 LIBerate trial, which enrolled a diverse population of >2,900 patients. Lerochol demonstrated sustained LDL-C reductions of ≥60% in patients with, or at very high or high risk of, cardiovascular disease and ≥59% in those with HeFH who have more severe LDL-C elevations. Lerochol’s monthly dosing and extended room-temperature stability of up to 3 months may enhance adherence compared with other PCSK9 inhibitors that require more frequent injections. These features are beneficial for managing long-term, intensive LDL-C reduction.

Emerging therapies such as Lerochol and evolving guideline recommendations both necessitate and enable a dynamic and individualized approach to hypercholesterolemia, particularly in patients with HeFH and high ASCVD risk. Incorporation of novel treatments into practice reflects a broader shift toward precision, goal-directed lipid management. Stay informed about emergent drug information, including treatment options for hypercholesterolemia, by exploring PDR by ConnectiveRx. You can also stay current by using the official PDR app, mobilePDR, which is available for free from your preferred app store.

FDA New Approvals

Adquey

The FDA has approved Adquey (difamilast) 1% ointment, for the topical treatment of mild-to-moderate atopic dermatitis in adults and pediatric patients aged 2 and older. Learn more about Adquey

Filkri

The FDA has approved Filkri (filgrastim-laha), a biosimilar to Neupogen (filgrastim), for patients with cancer receiving myelosuppressive chemotherapy; patients with acute myeloid leukemia receiving induction or consolidation chemotherapy; patients with cancer undergoing bone marrow transplantation; patients with severe chronic neutropenia; and patients acutely exposed to myelosuppressive doses of radiation (hematopoietic syndrome of acute radiation syndrome). Learn more about Filkri

Yuvezzi

The FDA has approved Yuvezzi (carbachol and brimonidine tartrate ophthalmic solution) 2.75%/0.1%, previously known as Brimochol PF, the first and only dual-agent eye drop for the treatment of presbyopia in adults. Learn more about Yuvezzi

FDA New Indications

Calquence

The FDA has approved Calquence (acalabrutinib) in combination with venetoclax as an all-oral, fixed-duration regimen for the treatment of adult patients with chronic lymphocytic leukaemia and small lymphocytic lymphoma. Learn more about Calquence

Darzalex Faspro

The FDA has approved Darzalex Faspro (daratumumab/hyaluronidase-fihj) in combination with bortezomib, lenalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. Learn more about Darzalex Faspro

Enzeevu

The FDA has approved an expanded label for Enzeevu (aflibercept-abzv), to include macular edema following retinal vein occlusion, diabetic retinopathy, and diabetic macular edema, along with the previously approved indication of neovascular (wet) age-related macular degeneration. Learn more about Enzeevu

Keytruda and Keytruda Qlex

The FDA has approved approved Keytruda (pembrolizumab) and Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) plus paclitaxel, with or without bevacizumab, for the treatment of adults with PD-L1+ (Combined Positive Score [CPS] ≥1), as determined by an FDA-authorized test, platinum-resistant epithelial ovarian, fallopian tube or primary peritoneal carcinoma, who have received one or two prior systemic treatment regimens. Learn more about Keytruda and Keytruda Qlex

Wakix

The FDA has approved Wakix (pitolisant) tablets for the treatment of cataplexy in pediatric patients aged 6 years and older with narcolepsy. Learn more about Wakix

FDA Labeling Changes

Afrezza

The FDA has approved an update to the Prescribing Information for Afrezza (insulin human) Inhalation Powder, revising recommendations for the starting mealtime dosage when patients switch from subcutaneous mealtime insulin regimens. Learn more about Afrezza

Nexplanon

The FDA has approved a supplemental New Drug Application for Nexplanon (etonogestrel implant), which is indicated for use by women of reproductive potential to prevent pregnancy. The sNDA extends the duration of use of Nexplanon for up to five years, an extension of the previous three-year indication. Learn more about Nexplanon

Rybelsus and Ozempic

The FDA has approved approved an update to the product labeling to change the name of the product from Rybelsus (formulation R2) to Ozempic (semaglutide) tablets 1.5mg, 4mg, and 9mg. The active ingredient remains the same semaglutide molecule. Rybelsus has been available since 2019, and bringing the oral and injectable options under the Ozempic name, the manufacturer is helping make it clear that both contain semaglutide from them and are approved to treat type 2 diabetes. Learn more about Rybelsus and Ozempic

Yescarta

The FDA has approved an update to the Yescarta (axicabtagene ciloleucel) prescribing information removing the previous Limitations of Use in patients with relapsed or refractory primary central nervous system lymphoma. Learn more about Yescarta

FDA New Dosing

Rybrevant Faspro

The FDA has approved as approved a new, simplified monthly dosing schedule for Rybrevant Faspro (amivantamab and hyaluronidase-lpuj). Learn more about Rybrevant Faspro

Venclexta

The FDA has approved the combination regimen of Venclexta (venetoclax) plus acalabrutinib for the treatment of previously untreated adults with chronic lymphocytic leukemia. Learn more about Venclexta

FDA Recalls

Shaman Botanicals Alkaloids Chewable Tablets

Shaman Botanicals, LLC is voluntarily recalling one lot (Lot B# AAW.501.3) of alkaloids chewable tablets-white vein to the consumer level. Recent testing showed that the alkaloids chewable tablets-white vein product contains 7-hydroxymitragynine in an amount more than the declared value of 7.5mg/tablet. Learn more about the Shaman Botanicals Alkaloids Chewable tablets recall

FDA Alerts

Epinephrine Nasal Solutions

The FDA is warning healthcare professionals not to use unapproved epinephrine nasal solutions manufactured by BPI Labs LLC and Endo USA. Healthcare professionals have confused these products with FDA-approved injectable epinephrine products for intravenous use. BPI Labs and Endo USA nasal solutions products should never be injected intravenously. Learn more about the epinephrine nasal solutions drug alert

Menopausal Hormone Therapies

The FDA has approved drug labeling changes to six menopausal hormone therapy products, also known as hormone replacement therapy, to clarify risk considerations for these drugs. Specifically, risk statements related to cardiovascular disease, breast cancer and probable dementia were removed from the “boxed warning,” the agency’s most prominent safety-related warning. Learn more about the menopausal hormone therapies with updated prescribing information

FDA REMS

Nexplanon

The FDA has approved a REMS for Nexplanon (etonogestrel implant). The goal of the Nexplanon REMS is to mitigate complications due to improper insertion and removal. Learn more about Nexplanon

Labeling Updates - No updates this month