Lovastatin

Effective for Medicare claims beginning April 1, 2026 LAKE ZURICH, Ill.--(BUSINESS WIRE)-- #CommittedToLife --Fresenius Kabi, a part of Fresenius, and a leading provider of essential medicines and medical technologies, announced today that the Centers for Medicare & Medicaid Services has issued indication-specific Healthcare Common Procedure Coding System (HCPCS) codes for Tyenne ® (tocilizumab-aazg) for the treatment of COVID-19. The new codes will be effective for Medicare claims for eligible patients administered Tyenne on April 1, 2026. These new COVID-19 HCPCS codes – Q0238 for injection, M0233 for intravenous infusion first-dose, and M0234 for intravenous infusion second-dose – will support billing and reimbursement for Tyenne when used in the treatment of COVID-19 in appropriate patients, consistent with its FDA-approved labeling. “Fresenius Kabi’s indication-specific codes for COVID-19 represent an important step in supporting provider access and streamlined reimbursement for Tyenne,” said Molly Benson, senior vice president, Biopharma, at Fresenius Kabi USA. “Clear coding helps facilitate efficient claims processing and reinforces our commitment to ensuring patients have access to important treatment options.” HCPCS codes are reimbursement codes used by healthcare providers and payers to process claims for drugs administered by injection, infusion, or other methods. These codes are used by Medicare, Medicaid, and commercial insurers to standardize claims submissions and reimbursement processes. Tyenne previously received a permanent, product-specific Q-code for its approved autoimmune indications. These indication-specific COVID-19 codes further support appropriate coding and reimbursement pathways across care settings. To learn more about how Fresenius Kabi provides comprehensive patient support, visit the KabiCare™ patient services hub . To learn more about Tyenne, please visit . About Tyenne ® , a tocilizumab biosimilar Tyenne ® (tocilizumab-aazg), a biosimilar to Actemra ® (tocilizumab), is a prescription medicine called an Interleukin-6 (IL-6) receptor antagonist. It was developed by Fresenius Kabi using advanced analytical and manufacturing technologies for use in the treatment of several autoimmune diseases, including rheumatoid arthritis, giant cell arteritis, polyarticular juvenile idiopathic arthritis, and systemic juvenile idiopathic arthritis. Serious infections leading to hospitalization or death including tuberculosis (TB), bacterial, invasive fungal, viral, and other opportunistic infections have occurred in patients receiving the product. Tyenne is contraindicated in patients with known hypersensitivity to tocilizumab products. For more information about Tyenne, please see the full prescribing information for the U.S. here , including Boxed Warning. IMPORTANT SAFETY INFORMATION RISK OF SERIOUS INFECTIONS Patients treated with Tyenne ® (tocilizumab-aazg) are at increased risk for developing serious infections that may lead to hospitalization or death, including tuberculosis (TB), bacterial, invasive fungal, viral, or other opportunistic infections. If a serious infection develops, interrupt Tyenne until the infection is controlled. Reported infections include: Active tuberculosis, which may present with pulmonary or extrapulmonary disease. Patients, except those with COVID-19, should be tested for latent tuberculosis before Tyenne use and during therapy (except patients with COVID-19). Treatment for latent infection should be initiated prior to Tyenne use. Invasive fungal infections, including candidiasis, aspergillosis, and pneumocystis. Patients with invasive fungal infections may present with disseminated, rather than localized, disease. Bacterial, viral and other infections due to opportunistic pathogens. The risks and benefits of treatment with Tyenne should be carefully considered prior to initiating therapy in patients with chronic or recurrent infection. Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with Tyenne, including the possible development of tuberculosis in patients who tested negative for latent tuberculosis infection prior to initiating therapy. CONTRAINDICATION Tyenne is contraindicated in patients with known hypersensitivity to tocilizumab products. WARNINGS AND PRECAUTIONS COVID-19: Monitor for signs and symptoms of new infections during and after treatment with Tyenne in patients with COVID-19. Limited information is available regarding the use of Tyenne in patients with COVID-19 and concomitant serious active infections. The risks and benefits of treatment with Tyenne in patients with COVID-19 and other concurrent infections should be considered. Gastrointestinal Perforations: Events of gastrointestinal (GI) perforation have been reported in clinical trials, primarily as complications of diverticulitis in RA patients. Use Tyenne with caution in patients who may be at increased risk for GI perforation. Promptly evaluate patients presenting with new-onset abdominal symptoms for early identification of GI perforation. Hepatotoxicity: Serious cases of hepatic injury have been observed in patients taking intravenous or subcutaneous tocilizumab. Some of these cases have resulted in liver transplant or death. Time to onset for cases ranged from months to years after treatment initiation. Most cases presented with marked elevations of transaminases (> 5 times ULN), and some cases presented with signs or symptoms of liver dysfunction and only mildly elevated transaminases. Treatment with Tocilizumab was associated with a higher incidence of transaminase elevations; increased frequency and magnitude of these elevations were observed when tocilizumab was used in combination with potentially hepatotoxic drugs (e.g., methotrexate). It is not recommended to initiate Tyenne treatment in RA, GCA, PJIA, and SJIA patients with elevated transaminases ALT or AST greater than 1.5x ULN. In patients who develop elevated ALT or AST greater than 5x ULN discontinue Tyenne. Patients who are hospitalized with COVID-19 may have elevated AST or ALT levels. Multiorgan failure with involvement of the liver is recognized as a complication of severe COVID-19. The decision to administer Tyenne should balance the potential risks of acute treatment with Tyenne against the potential benefit of treating COVID-19. It is not recommended to initiate TYENNE treatment in COVID-19 patients with elevated ALT or AST above 10x ULN. Monitor ALT and AST during treatment. Measure liver tests promptly in patients who report symptoms that may indicate liver injury. If the patient is found to have abnormal liver tests, Tyenne treatment should be interrupted. Tyenne should only be restarted in patients with another explanation for the liver test abnormalities after normalization of the liver tests. Laboratory Parameters: Laboratory monitoring is recommended due to potential consequences of treatment-related laboratory abnormalities in neutrophils, platelets, lipids, and liver function tests. Dosage modifications may be required. Neutropenia: Treatment with tocilizumab products was associated with a higher incidence of neutropenia. It is not recommended to initiate Tyenne treatment in RA, GCA, PJIA, and SJIA patients with a low neutrophil count i.e., absolute neutrophil count (ANC) less than 2000 per mm 3 . In patients who develop an ANC less than 500 per mm 3 treatment is not recommended. It is not recommended to initiate Tyenne treatment in COVID-19 patients with an ANC less than 1000 per mm 3 . Neutrophils should be monitored. Thrombocytopenia: Treatment with tocilizumab products was associated with a reduction in platelet counts. It is not recommended to initiate Tyenne in RA, GCA, PJIA, and SJIA patients with a platelet count below 100,000 per mm 3 . In patients who develop a platelet count less than 50,000 per mm 3 , treatment is not recommended. It is not recommended to initiate Tyenne treatment in COVID-19 patients with a platelet count less than 50000 per mm 3 . Platelets should be monitored. Elevated Liver Enzymes: It is not recommended to initiate Tyenne treatment in patients with elevated transaminases ALT or AST >1.5x ULN. In patients who develop elevated ALT or AST >5x ULN, treatment is not recommended. Lipid Abnormalities: Treatment with tocilizumab products was associated with increases in lipid parameters such as total cholesterol, triglycerides, LDL cholesterols, and/or HDL cholesterol. Immunosuppression: The impact of treatment with tocilizumab products on the development of malignancies is not known, but malignancies were observed in clinical studies with tocilizumab. Tyenne is an immunosuppressant, and treatment with immunosuppressants may result in an increased risk of malignancies. Hypersensitivity Reactions : Hypersensitivity reactions, including anaphylaxis, have been reported in association with tocilizumab and anaphylactic events with a fatal outcome have been reported with intravenous infusion of Tocilizumab. Additionally, serious cutaneous reactions, including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), have been reported in patients with autoinflammatory conditions treated with Tocilizumab products. Tyenne for intravenous use should only be infused by a healthcare professional with appropriate medical support to manage anaphylaxis. For Tyenne subcutaneous injection, advise patients to seek immediate medical attention if they experience any symptoms of a hypersensitivity reaction. If anaphylaxis or other hypersensitivity reaction occurs, stop administration of Tyenne immediately and discontinue Tyenne permanently. Do not administer Tyenne to patients with known hypersensitivity to Tyenne. Demyelinating Disorders: The impact of treatment with tocilizumab products on demyelinating disorders is not known, but multiple sclerosis and chronic inflammatory demyelinating polyneuropathy were reported rarely in clinical studies. Monitor patients for signs and symptoms of demyelinating disorders. Prescribers should exercise caution in considering the use of Tyenne in patients with preexisting or recent-onset demyelinating disorders. Active Hepatic Disease and Hepatic Impairment: Treatment with Tyenne is not recommended in patients with active hepatic disease or hepatic impairment. Vaccinations : Avoid use of live vaccines concurrently with Tyenne. No data are available on the secondary transmission of infection from persons receiving live vaccines to patients receiving Tyenne or on the effectiveness of vaccination in patients receiving Tyenne. Patients should be brought up to date on all recommended vaccinations prior to initiation of Tyenne therapy, if possible. ADVERSE REACTIONS Most common adverse reactions (incidence of at least 5%): upper respiratory tract infections, nasopharyngitis, headache, hypertension, increased ALT, injection site reactions. DRUG INTERACTIONS In GCA patients, no effect of concomitant corticosteroid on tocilizumab exposure was Observed. Cytochrome P450s in the liver are down-regulated by infection and inflammation stimuli including cytokines such as IL-6. Inhibition of IL-6 signaling in RA patients treated with Tyenne may restore CYP450 activities to higher levels than those in the absence of Tyenne leading to increased metabolism of drugs that are CYP450 substrates. Exercise caution when co-administering Tyenne with CYP3A4 substrate drugs where decrease in effectiveness is undesirable, e.g., oral contraceptives, lovastatin, atorvastatin, Etc. USE IN PREGNANCY The limited available data with tocilizumab products in pregnant women are not sufficient to determine whether there is a drug-associated risk for major birth defects and miscarriage, or other adverse maternal or fetal outcomes. You may report side effects to the FDA at (800) FDA-1088 or . You may also report side effects to Fresenius Kabi at (800) 551-7176. INDICATIONS Tyenne is indicated for the treatment of adult patients with moderately to severely active rheumatoid arthritis (RA) who have had an inadequate response to one or more disease-modifying anti-rheumatic drugs (DMARDs). Tyenne is indicated for the treatment of giant cell arteritis (GCA) in adult patients. Tyenne is indicated for the treatment of active polyarticular juvenile idiopathic arthritis (PJIA) in patients 2 years of age and older. Tyenne is indicated for the treatment of active systemic juvenile idiopathic arthritis (SJIA) in patients 2 years of age and older. Tyenne is indicated for the treatment of chimeric antigen receptor (CAR)-T cell-induced severe or life-threatening cytokine release syndrome in adults and pediatric patients 2 years of age and older. Tyenne is indicated for the treatment of coronavirus disease 2019 (COVID-19) in hospitalized adult patients who are receiving systemic corticosteroids and require supplemental oxygen, non-invasive or invasive mechanical ventilation, or extracorporeal membrane oxygenation (ECMO). Please see additional Important Safety Information in full Prescribing Information , including BOXED WARNING . About Fresenius Kabi As a global healthcare company, Fresenius Kabi is Committed to Life. The company’s products, technologies, and services are used for the therapy and care of patients with critical and chronic conditions. With more than 41,000 employees and present in more than 100 countries, Fresenius Kabi’s expansive product portfolio focuses on providing access to essential medicines and technologies. In Biopharma, Fresenius Kabi offers cutting-edge biosimilars for autoimmune diseases and oncology. With leading market positions in Clinical Nutrition, a broad portfolio of enteral and parenteral products makes a distinct difference in patients’ nutritional status. In MedTech, the company provides vital infusion pumps, cell and gene therapy devices, disposables, and more. Fresenius Kabi is a global leader in supplying blood collection bags and devices, supporting blood banks and health care facilities worldwide. The company’s I.V. Generics and Fluids for infusion therapy help save millions of lives every year, in emergency medicine, surgery, oncology, and intensive care. Fresenius Kabi takes a holistic approach to health care and uniquely combines experience, expertise, innovation, and dedication – making a difference in the lives of 450 million patients annually. With the #FutureFresenius strategy, the company is developing, producing, and selling new products and technologies and aspires to expand its position as a leading global provider of therapies, improve patient care, generate sustainable value for stakeholders – shaping the future of healthcare. Fresenius Kabi is part of the Fresenius Group, founded in 1912, along with Helios and Quirónsalud. As ONE team, the companies in the Fresenius Group are committed to providing lifesaving and life-changing healthcare solutions on a global scale. For more information, please visit . To learn about U.S. career opportunities at Fresenius Kabi, visit us at and follow us on LinkedIn and Facebook . This release contains forward-looking statements that are subject to various risks and uncertainties. Future results could differ materially from those described in these forward-looking statements due to certain factors, e.g., changes in business, economic and competitive conditions, regulatory reforms, results of clinical trials, foreign exchange rate fluctuations, uncertainties in litigation or investigative proceedings, and the availability of financing. Fresenius Kabi does not undertake any responsibility to update the forward-looking statements in this release. Contacts Media contact Joanie Clougherty (614) 717-5741 Joan.Clougherty@fresenius-kabi.com

With the power to promote plaque build-up, blood clots and inflammation, Lp(a) has been likened to a “triple-headed monster.” \n In the early 1960s, Norwegian physician Kåre Berg, M.D., was trying to identify new blood types when he accidentally discovered a lipoprotein with perplexing properties. Similar to cholesterol, but not quite the same, and also the lookalike of a clot-busting protein, the molecule still vexes researchers many decades later. It also might just revolutionize cardiovascular medicine as we know it.The potential impact of medicines that lower lipoprotein(a)—abbreviated as Lp(a) and often read as “L-P-little A”—is obvious. Elevated Lp(a) is a known risk factor for a range of bad cardiac outcomes, from heart attacks and strokes to heart valve malfunctions. And the scale of the problem is almost too large to fathom: an estimated 20% of the global population has Lp(a) levels that put them at risk. Guidelines from a suite of expert groups, led by the American College of Cardiology and American Heart Association, now recommend that everyone have their Lp(a) levels tested at least once in their life.Unlike cholesterol, Lp(a) is almost entirely genetically controlled, meaning it can’t be lowered with a new diet or an exercise regimen. But Lp(a)’s genetic control, as well as its manufacturing site in the liver, make it a prime candidate for targeting by small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs).Should the Lp(a)-lowering candidates now in the clinic reach their full potential, they could surpass statins—the most prescribed medications in the world—in their use, multiple experts told Fierce Biotech. “In the U.S., it\'s 65 million people with high Lp(a) that would be theoretically eligible,” Sam Tsimikas, M.D., cardiovascular leader at Ionis Pharmaceuticals and a pioneer of Lp(a) drug development, told Fierce. “It\'s going to be huge.”The first pivotal trial set to read out is for Novartis and Ionis’ ASO pelacarsen, with data expected in the next few months; candidates from Amgen and Eli Lilly will follow over the coming years. Should pelacarsen’s phase 3 Horizon trial succeed, it would trigger a tidal wave of interest in the Lp(a) field, experts agreed. But while pelacarsen could be approved as early as next year, there would still be a long way to go before the Lp(a) drug class as a whole ascends to the mega-blockbuster level of statins.“There\'s a couple of things that really need to happen to get to that market opportunity,” Myles Minter, Ph.D., a healthcare analyst with William Blair, told Fierce. Cracking the primary cardiac prevention market could be a challenge, Minter and others said, and much still remains unknown about Lp(a)’s relationship with different kinds of heart risks. In fact, the basic question of what Lp(a) is supposed to do in the body remains unanswered.But even if statin-like success remains unattainable, Minter added, “in my book, these are all blockbuster opportunities regardless.”And Lp(a) innovation isn\'t stopping there. AstraZeneca is pursuing a combination of a PCSK9 inhibitor and an Lp(a) disruptor, as is the recently rebranded cardio outfit Thalia Therapeutics.David Solomon, Ph.D., the former CEO of GLP-1 biotech Zealand Pharma, who now leads Thalia, thinks the Lp(a) market could even top the current obesity frenzy.Just as GLP-1 medicines have come of age in recent years, “I think in the next five to 20 years, this field will come to fruition,” Solomon told Fierce. “This is just a huge market opportunity.” Mystery molecule After Berg’s initial discovery of Lp(a) in 1963, the field went quiet for about a decade. That silence was shattered in 1974, when researchers realized that the molecule wasn’t just present in some people, as Berg had thought, but was in fact found in everyone. From there, its relationship with heart attacks was established, and over the subsequent decades, its ability to potentiate multiple kinds of cardiac events was solidified.The signature “little a” of Lp(a) refers to apolipoprotein(a), the key feature of Lp(a) that makes the molecule so tricky to study. Apo(a) consists of units called kringles—named after a twisty Northern European pastry—some of which repeat. Different genetic variants of the apo(a) gene lead to different numbers of kringle repeats, which in turn produces Lp(a) molecules of different sizes. When people have short Lp(a) molecules, they tend to build up more easily in the blood, leading to elevated levels and increased cardiovascular risk. Marlys Koschinsky, Ph.D., an Lp(a) expert at Western University in Ontario, Canada, has spent decades unraveling Lp(a)’s structure and how it relates to its ability to cause cardiac harm, going back to a postdoctoral position at Genentech that she took in 1988. She calls Lp(a) a “triple-headed monster” because it can clog arteries using its cholesterol component, enable blood clots to build with its apo(a) component by interfering with the clot-destroying protein plasminogen and wriggle into blood vessels to trigger inflammation.Ionis’ Tsimikas agrees with this monstrous characterization. “Lp(a) is, in many ways, a diabolical compound,” he said. Despite being discovered 63 years ago, scientists still aren’t sure how the body breaks it down or if it has any dedicated receptors that it binds to on the surface of cells.  Part of the problem for a while was that there was no reliable way to measure Lp(a); all those repeating kringles could attract multiple antibodies used to quantify it, making one Lp(a) molecule look like multiple. That issue, at least, has been solved now, and Roche sells a reliable assay for measuring the molecule in blood.“You\'ve got to be rather insane, really, to spend a career trying to work on it,” Koschinsky told Fierce. “All the kringle repeats, the isoform size variability—and people for a long time didn\'t even believe that it was a risk factor in the clinic.”With so many well-documented negative effects, one would be forgiven for wondering why, exactly, the human body makes any Lp(a) at all. Tsimikas thinks the molecule’s ability to promote blood clots may have, at one point, helped stanch bleeding during childbirth.“It\'s not relevant now, because pretty much everybody gives birth in a hospital, but in the old days, women died of childbirth from hemorrhage,” he said. Under these conditions, more Lp(a) meant less bleeding, with surviving mothers then able to pass on their genes for elevated Lp(a) to their offspring, he posited.Tsimikas’ fellow Lp(a) pioneer Koschinsky, though, remains unconvinced that Lp(a) has any use whatsoever. The molecule is found only in humans and certain species of monkeys. In fact, some people have extremely low levels of it with no apparent problems—which makes Koschinsky suspect it doesn’t serve any deep-seated evolutionary purpose. “I guess there\'s people who believe, like there\'s also people who believe in UFOs, that it\'s got to have some kind of a biological function,” she said. “If there is something, we haven\'t found it.” Any day now All the experts Fierce spoke with agreed that Novartis and Ionis’ Horizon trial is a pivotal test for the Lp(a) field, albeit not necessarily a make-or-break one.Horizon is a secondary prevention trial, focused on 8,323 patients with established cardiovascular disease and elevated Lp(a), most of whom have had a heart attack or stroke before. The goal is for pelacarsen treatment to lower Lp(a) levels and demonstrate a concomitant reduction in risk of a second cardiac event.The enrolled patients have an average Lp(a) level of 108 mg/dl, according to a 2025 publication. With pelacarsen expected to lower Lp(a) by around 70% based on past data, William Blair’s Minter said, the vast majority of treated patients should get below 50 mg/dl, the generally accepted level at which Lp(a) is considered too high.“You\'re trying to stop the second event,” Minter said. “We\'re going to find out whether interventional lowering of around about 70%, 80%, [depending] on the exposure of pelacarsen, is enough to do it.”Should Horizon succeed, it will offer proof of the hypothesis that therapeutically lowering Lp(a) can reduce cardiovascular risk, Western University\'s Koschinsky said.“That hypothesis has been out there for years,” Koschinsky said. And while a positive Horizon outcome won’t definitively prove it for all kinds of cardiovascular events, the result will likely spur skeptical providers to finally start testing their patients’ Lp(a) levels.“People are going to really be nervous [that] if they\'re not testing it, then they\'re really not fulfilling their mandate to their patients,” said Koschinsky, who was first author on the National Lipid Association’s 2019 statement advocating for routine Lp(a) measurement.The many mysteries that remain swirling around Lp(a) frustrate clinicians, she added, who are still waiting for definitive proof that lowering levels of the lipoprotein is worth it. “You\'ve got to change hearts and minds on this,” she said. The other experts Fierce spoke with agreed that a Horizon success would undoubtedly spark significant interest in Lp(a) testing and treatment.“You\'re going to see testing skyrocket,” Ionis’ Tsimikas said, “and then there\'ll be a lot of interest to treat high-risk primary prevention,” even though Horizon is addressing secondary prevention. He noted that he sees many patients at his clinic who have elevated Lp(a) and family histories of heart problems.“They all want to have some therapy for their problem,” he said. “We\'re going to have to deal with a lot of demand for access to this drug.” If everything had gone according to plan, Horizon would have already provided an answer to the Lp(a) question. Novartis initially expected data to read out last year, following delays due to the COVID-19 pandemic, but Tsimikas told Fierce that the trial should wrap up in the next few months. That’s because the study won’t stop until a certain number of cardiac events have happened, and the chances of heart attacks and strokes in the patient population have changed over time.“When the trial was designed, the power calculations were based on Fourier,” Tsimikas explained, referring to Amgen’s phase 3 trial for its PCSK9 inhibitor Repatha.To match the Fourier placebo group’s yearly cardiac event rate of 4.6%, the Horizon team calculated that they’d need to follow patients for around 4.25 years and accrue 993 events, he said.However, in the time it took to get the trial off the ground, the cardio risk field changed, and Horizon’s enrolled patients have a baseline level of LDL cholesterol far below that of Fourier, putting them at a lower overall risk of heart attacks and strokes.“It may actually not make a difference in the readout of the trial, even though the event rates are lower, because the event rates are going down because of LDL, not because of Lp(a),” Tsimikas said. LDL and Lp(a) are independent risk factors, as far as we know.It is possible that the relationship between LDL, Lp(a) and cardiac risk could change at very low levels of LDL, he added, but that won’t be clear until the data finally come in.Horizon “will push the field either forward or backwards, depending on the result,” Rafael Zubirán, M.D., a researcher in the lipoprotein metabolism laboratory at the National Heart, Lung and Blood Institute, told Fierce. But with Lp(a)’s link to bad cardiac outcomes so clear, even a fail from pelacarsen likely wouldn’t stop the field in the long run.“It won\'t be the end of [Lp(a)] if it fails; it will be a huge win if it does provide a good reduction,” Zubirán said.  Follow the leader While Novartis and Ionis are, for now, focusing pelacarsen on patients who have had cardiac events already, their competitors are hot on their heels, with an eye toward the lucrative primary prevention market.Amgen’s siRNA olpasiran is set to read out a secondary prevention trial in December and a primary prevention trial in 2031, both phase 3, while Lilly’s siRNA lepodisiran has a phase 3 primary prevention trial set to wrap up in 2029.Amgen licensed olpasiran from Arrowhead Pharmaceuticals back in 2016, while Lilly developed lepodisiran through a 2018 research pact with Dicerna Pharmaceuticals (since acquired by Novo Nordisk). Ionis, meanwhile, published the first results of the ASO that became pelacarsen in 2011.  Amgen and Lilly’s next-gen molecules are both more potent than pelacarsen, so far reducing Lp(a) levels by more than 90%. Whether this more drastic reduction translates to improved risk reduction relative to pelacarsen is a key open question, as is whether or not dropping Lp(a) to near zero causes any unwanted side effects.Even if the improved standard of care in cardiac risk reduction—thanks to statins, PCSK9 inhibitors and aspirin—dulls pelacarsen’s apparent efficacy in Horizon, the Lp(a) cat is already out of the bag. Ionis’ Tsimikas doesn’t think a negative result for Horizon would matter to Amgen and Lilly’s trials.“I don\'t think anybody\'s going to stop,” he said. “Those are going to continue, no matter what happens with Horizon.”By blazing the Lp(a) trail, Ionis and partner Novartis now enjoy a lead on Amgen of about a year and a half. But even before a positive Horizon result potentially sparks an Lp(a) gold rush, others are already piling onto the bandwagon. In addition to lepodisiran, Lilly is also testing an oral small molecule called muvalaplin, with its own phase 3 trial set to conclude in 2031. It’s the possibility of an Lp(a)-lowering pill that most excites William Blair’s Minter. That would make the \"holy grail\" that AstraZeneca is pursuing, a combo of an oral PCSK9 inhibitor and an oral Lp(a) disruptor, much closer to reality. AstraZeneca has such a PCSK9 inhibitor in phase 3 development, known as AZD0780, and licensed a preclinical Lp(a) asset from CSPC Pharmaceutical Group in 2024.“That\'s your combination therapy moving forward, that basically manages your apolipoproteins for life,” Minter said.The potential of a combo therapy also piqued Thalia\'s interest. The U.K. biotech rebranded from N4 Pharma in February, with a focus on a dual-acting siRNA meant to inhibit both PCSK9 and Lp(a). While still preclinical, Thalia’s new CEO, David Solomon, has high hopes for the approach as a once-yearly cardiovascular risk reducer.“The dual is a really strong approach,” he told Fierce, comparing it to the obesity field that is now awash with assets aiming for GLP-1, amylin and other target combos. And even though Thalia is far behind the competition, Solomon isn’t concerned.“In the world of statins, Mevacor was first, and everyone thought Merck had done it,” he said. “But the most successful statin was the number six statin, which was [AstraZeneca’s] Crestor. There\'s room in cardiovascular medicine for multiple medicines against similar targets that address a lot of unmet need.”With so much competition swirling, Ionis is committed to staying on top of the Lp(a) field, Tsimikas said. After licensing a planned follow-up to pelacarsen to Novartis in 2023, the Big Pharma has since handed the asset back to Ionis. This decision was partly driven by Novartis\' desire to move pelacarsen follow-ons into the clinic quickly, he explained, with the next-gen Ionis asset still being early in development.“We\'re not going to sit on it,” Tsimikas said. “We want to stay the Lp(a) leaders, in many ways. Whether it\'s siRNA, gene editing, whatever.”