Latest news with #LDL
Medscape
11 hours ago
- Business
- Medscape
No, KETO-CTA Study Did Not Upend Causal Evidence on ASCVD
Few argue that eating too many carbohydrates is a key cause of the obesity crisis. The ideal solution would be to moderate carbohydrate intake to the amounts consumed by Sicilians. But some people have gone to the extreme of eliminating nearly all carbs. One result of eating only fat and protein is ketosis. Another may be a rise in atherogenic lipid particles, such as low-density lipoprotein cholesterol (LDL-C). Lean-Mass Hyperresponders Authors of the observational KETO-CTA study purport to show that a subgroup of people on keto diets who sustain serious increases in lipids may be protected from progression of atherosclerosis. This, despite nearly a half-century of evidence that higher LDL-C levels lead to coronary artery disease. They deemed this subgroup lean-mass hyperresponders(LMHRs). The idea stems from the observation that there may be heterogeneity in the LDL-C response to a keto diet. A meta-analysis (by some of the KETO-CTA authors) included 41 trials involving low-carbohydrate diets and found that rises in LDL-C turned largely on baseline BMI. Specifically, for trials including patients with a mean baseline BMI < 25, LDL-C increased by 41 mg/dL; for trials with a mean BMI of 25-35, LDL-C did not change; and for trials with a mean BMI ≥ 35, LDL-C decreased by 7 mg/dL. The association of baseline BMI with LDL-C was much stronger than the effect of dietary saturated fat. In the LMHR group, the rise in LDL-C can be striking, sometimes well north of 300 mg/dL. The obvious question is whether (or how much) this raises atherosclerotic risk. The best way to study this question would be long-term trials where people are randomly assigned and are adherent to specific diets. It would take years to sort out the effects because atherosclerosis is slowly progressive. Another way, perhaps the only realistic way, is to use surrogate markers of atherosclerosis, which now include imaging of the vessel itself. The KETO-CTA Study The KETO-CTA study, published in JACC: Advances , garnered lots of attention on social media. First, I will tell you the topline findings and then the critical appraisal. The authors aimed to study the association between plaque progression and its predicting factors in participants with an LMHR pattern. Plaque progression was measured on coronary CT imaging performed at baseline and repeated at 1 year. Images were blindly read, and software was required to quantify plaque characteristics. The authors recruited 100 individuals with the LMHR phenotype who had been on a ketogenic diet for at least 2 years to participate in the single-arm observational study. To qualify, they had to have a low BMI and a keto-induced LDL-C ≥ 190 mg/dL, HDL-C ≥ 60 mg/dL, triglycerides ≤ 80 mg/dL, and evidence of being metabolically healthy (normal CRP and A1c). The keto-induced criteria required that individuals had an LDL-C < 160 mg/dL before adopting the diet. They don't say how many individuals they screened to find these participants. Those included in the study had striking numbers. Despite an average BMI of 22, they had mean LDL-C levels of 254 mg/dL, HDL-C of 89 mg/dL, and triglycerides of 67 mg/dL. The average age was 55 years and most were men. They could not be on lipid-lowering therapy, which is remarkable for patients with very high LDL-C. Adherence to the keto diet was high and confirmed by beta-hydroxy-butyrate levels. Results Over the year, there were no substantial changes in ApoB or BMI, which you would expect because participants were on a stable keto diet. The presentation of the results was peculiar. The authors preregistered the study and declared the primary endpoint as the change in noncalcified plaque volume. But they did not formally present this endpoint. Instead, they gave the median change in percent atheroma volume, which was 0.8%. The primary endpoint was presented in a figure in which a horizontal line represented each individual. No quantification was given, but visual inspection of the graph revealed that most individuals sustained an increase in noncalcified plaque volume. The lack of clear presentation of the primary endpoint caused a stir online. This led the first author to present it in on X. The numerical pooled change in noncalcified plaque burden was an increase of 18.8 mm3. In the manuscript, they emphasized the correlations and lack of correlations. Neither the change in ApoB throughout the study nor the ApoB at the beginning of the study was associated with the change in noncalcified plaque volume. There was also no correlation between LDL-C and change in noncalcified plaque volume. The main finding was that the baseline coronary artery calcium score was positively associated with change in noncalcified plaque volume as was baseline plaque. They list four differences between the LMHR subgroup and people with elevated lipids from other metabolic risk factors: Difference 1: Their LDL-C and ApoB elevations are dynamic and result only from the metabolic response to carb restriction. Their LDL-C and ApoB elevations are dynamic and result only from the metabolic response to carb restriction. Difference 2: They are normal weight and metabolically healthy (ie, they don't have obesity, diabetes or insulin resistance). They are normal weight and metabolically healthy (ie, they don't have obesity, diabetes or insulin resistance). Difference 3: Their high LDL-C and ApoB are part of a lipid triad that includes high HDL-C and low triglycerides, representing a metabolic signature of a distinct physiologic state. Their high LDL-C and ApoB are part of a lipid triad that includes high HDL-C and low triglycerides, representing a metabolic signature of a distinct physiologic state. Difference 4: The degree of this phenotype appears inversely related to BMI ('leanness'), consistent with the idea that it is a metabolic response to carbohydrate restriction that is accentuated in leaner, more metabolically healthy persons. The authors go on to make highly provocative conclusions, such as: Conclusion 1: The LMHR population constitutes a unique and important natural experiment evaluating the lipid heart hypothesis in an unprecedented manner. The LMHR population constitutes a unique and important natural experiment evaluating the lipid heart hypothesis in an unprecedented manner. Conclusion 2: The data are consistent with the notion that elevated ApoB, even at extreme levels, does not drive atherosclerosis in a dose-dependent manner in this population of metabolically healthy individuals. The data are consistent with the notion that elevated ApoB, even at extreme levels, does not drive atherosclerosis in a dose-dependent manner in this population of metabolically healthy individuals. Conclusion 3: These insights can facilitate personalized treatment and risk-mitigation strategies based on modern, cost-effective cardiac imaging. For instance, LMHRs with CAC = 0 at baseline (n = 57) constitute a low-risk group for plaque progression, despite high LDL-C. These insights can facilitate personalized treatment and risk-mitigation strategies based on modern, cost-effective cardiac imaging. For instance, LMHRs with CAC = 0 at baseline (n = 57) constitute a low-risk group for plaque progression, despite high LDL-C. Conclusion 4: Because of the strong correlation of baseline coronary calcium with progression of noncalcified plaque, they coin the phrase plaque begets plaque. 6 Reasons the Keto-CTA Conclusions Are Problematic You don't have to be an expert in lipids, atherosclerosis, or imaging to oppose these conclusions. The study has limitations, but the main problem is the authors' outsized claims. I will outline six reasons why their conclusions are problematic: First, the primary endpoint of change in noncalcified plaque volume went up. The increase of 18.8 mm3 was 2.5 times higher than they predicted in their study protocol. If you believe that this endpoint is a great surrogate, the results are ominous. Second, imaging tests are almost always terrible surrogates. To assess risk, you need to measure cardiovascular events. Small, uncontrolled studies are fine, but you cannot claim clinical importance just because you weaved a nice story about high LDL-C in LMHRs being different from high LDL-C in other patients. Third, we have about 70 years of data supporting LDL-C being causal for atherosclerosis. Nearly every Bradford Hill criterion for causation is met for LDL-C and atherosclerosis. To claim an exception, you need more rigorous evidence than KETO-CTA. Fourth, assuming you believe the plaque images are precise, reproducible, and clinically relevant, KETO-CTA suffers from a lack of control. All they had to do is recruit a group of people eating another type of diet (eg Mediterranean diet) and make a comparison. Fifth, the authors don't tell us how many people they screened to find these 100 LMHRs. I get the sense they are a highly selected bunch. Sixth, the question of heart health from a specific diet will be difficult to sort out. Nutritional studies always are. A randomized trial in a prison might work, but cardiac event rates in young people, even with keto-induced-high LDL-C, will be infrequent. What's more, the LMHR group surely do other things that affect heart disease, like exercise, not smoking, etc. One final comment on the authors' messaging. It's been egregious and antiscientific. Their rhetoric and spin outdo some of the most hyped late-breaking trials. This was a small, noncontrolled observational study wherein the primary endpoint went the wrong way. It's nowhere near close to upending decades of causal evidence on the role of LDL-C and atherosclerosis. The journal editors and peer reviewers failed to modulate the outsized conclusions. I don't know what the solution is for this type of behavior, but I oppose it in the strongest terms.
NBC News
07-05-2025
- Health
- NBC News
New cholesterol drug lowers LDL when statins aren't enough, study finds
A new medication that combines an already approved drug with a new unapproved one has been shown to cut the level of LDL, or 'bad' cholestero l, when statins aren't helping enough. In the Phase 3 trial, Cleveland Clinic researchers found that the combination of the new drug, obicetrapib, with an established medication, ezetimibe, reduced low-density lipoprotein (LDL) cholesterol levels by 48.6% after about three months' use — producing more effective results than either drug alone. Ezetimibe is a cholesterol-lowering drug that is often prescribed with statins to reduce LDL even more. The research was presented Wednesday during a late-breaking science session at the annual meeting of the European Atherosclerosis Society in Glasgow, Scotland, and simultaneously published in The Lancet. In the multicenter clinical trial, the lead researcher, Dr. Ashish Sarraju, a preventive cardiologist at the Cleveland Clinic, and his colleagues enrolled 407 patients with a median age of 68 with LDL cholesterol levels greater than 70 mg/dL even though they had taken medication to lower it. The participants were randomly assigned to four groups: a group for a pill that combined obicetrapib with ezetimibe, a group for each of the drugs separately and a placebo group. All participants continued on the medications they were taking before they started the trial, along with the medications being studied. The reason: Some people have to take a number of prescriptions to get LDL down to desired levels. 'We need to give patients and their doctors all the options we can to try to get LDL under control if they are at risk for, or already have, cardiovascular disease,' Sarraju said. 'In higher-risk patients, you want to get LDL down as quickly as possible and keep it there as long as possible.' High-risk patients either had had strokes or heart attacks or were likely to in the future. For that reason, the researchers enrolled patients in the trial who, despite already being on statins or even high-intensity statins, still had LDL levels that were too high. The hope is that lowering LDL levels will reduce the risk of adverse cardiovascular events such as strokes and heart attacks. According to the American Heart Association, the optimal total cholesterol level for an adult is about 150 mg/dL, with LDL levels at or below 100 mg/dL ('dL' is short for 'deciliter,' or a tenth of a liter). For high-risk patients, Sarraju recommends an LDL no higher than 70 mg/dL. The trial was funded by the maker of obcetrapib, Netherlands-based NewAmsterdam Pharma. It expects to have conversations with the Food and Drug Administration about approval for the new combo drug 'over the course of the year,' a spokesperson said. A multitude of modifiable factors can result in high LDL, such as a diet high in saturated fats, processed foods and fried foods; being overweight; smoking; and older age. Dr. Robert Rosenson, director of lipids and metabolism for the Mount Sinai Health System in New York City, said other drugs in the same class have failed to reduce heart attacks or stroke, 'but I am cautiously hopeful.' The drugmaker is currently running an additional trial to determine if the combo drug not only lowers cholesterol but also protects against adverse heart events. While lifestyle changes can help bring down LDL, levels remain stubbornly high for some people. Only 20% of patients at high risk of heart disease are able to manage their LDL, said Dr. Corey Bradley, a cardiologist at the Columbia University Vagelos College of Physicians and Surgeons. Heart disease is the leading cause of death for adults in the United States. 'High LDL is one of the leading risk factors for heart disease, and we have such a poor handle on controlling that risk,' Bradley said. 'Many people have such a high LDL they will require multiple agents to control it.'
Yahoo
06-05-2025
- Health
- Yahoo
CRISPR Therapeutics Provides First Quarter 2025 Financial Results and Announces Positive Top-Line Data from Phase 1 Clinical Trial of CTX310™ Targeting ANGPTL3
A single dose of CTX310 demonstrated dose-dependent decreases in ANGPTL3, TGs, and LDL. Based upon ANGPTL3 knockdown, DL1 and DL2 were minimally active doses, whereas treatment at DL3 and DL4 resulted in reductions of up to 75% of baseline levels in ANGPTL3. CTX310 has been well-tolerated, with no treatment-related severe adverse events (SAEs) and no grade ≥3 adverse events (AEs) reported. No clinically significant changes in alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, or platelets were observed at any dose level. There were no dose-dependent trends in any of these laboratory measurements. Top-line data reported today are from the first 10 patients across the first four cohorts (lean body weight-based doses of DL1 [0.1 mg/kg], DL2[0.3 mg/kg], DL3 [0.6 mg/kg] and DL4 [0.8 mg/kg]) with at least 30 days of follow-up for each participant as of a data cutoff date of April 16, 2025. CTX310 is in an ongoing Phase 1 first-in-human dose escalation clinical trial targeting ANGPTL3 in four patient groups with elevated LDL, TG or both including homozygous familial hypercholesterolemia (HoFH), severe hypertriglyceridemia (sHTG), heterozygous familial hypercholesterolemia (HeFH), or mixed dyslipidemias (MDL) with levels of TG (>300 mg/dL) and/or LDL-C (>100 mg/dL); >70 mg/dL for subjects with ASCVD. TG and LDL, both of which are validated as surrogate endpoints for clinical benefit and accepted by regulatory agencies, were assessed at various timepoints. CTX310™ targets ANGPTL3, a gene that encodes for key protein involved in the regulation of low-density lipoprotein (LDL) and triglyceride (TG) levels – both well-established risk factors for atherosclerotic heart disease (ASCVD). Loss-of-function mutations in ANGPTL3 are associated with significantly reduced levels of LDL and TGs, as well as reduced risk of ASCVD, without adverse effects on overall health. In the U.S. alone, more than 40 million patients are affected by elevated LDL, severely elevated TGs or both – representing a large addressable patient population. CTX310 is initially focused on a high-risk subset of this group with the greatest unmet medical need and limited effective treatment options. 'CRISPR Therapeutics remains focused on executing our strategic priorities and advancing our portfolio of innovative therapies. We are highly encouraged by the initial data from our Phase 1 trial for CTX310, which demonstrates the power of our in vivo gene editing platform to deliver paradigm changing medicines to patients with serious cardiovascular disease,' said Samarth Kulkarni, Ph.D., Chairman and Chief Executive Officer of CRISPR Therapeutics. 'Additionally, we are pleased with the continued progress of Casgevy and the broader pipeline, and we look forward to sharing further clinical updates in the months ahead.' ZUG, Switzerland and BOSTON, May 06, 2025 (GLOBE NEWSWIRE) -- CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, today reported financial results for the first quarter ended March 31, 2025. -Clinical trials ongoing for next-generation CAR T product candidates, CTX112™ and CTX131™, targeting CD19 and CD70 across multiple indications; broad updates for CTX112 in oncology and autoimmune diseases expected mid-2025 with CTX131 updates also expected in 2025- -CASGEVY ® continues to gain momentum; more than 65 authorized treatment centers (ATCs) activated globally for CASGEVY, and more than 90 patients have had cells collected across all regions; new patient initiations expected to grow significantly in 2025- -Initial CTX310™ Phase 1 clinical data demonstrates dose-dependent decreases in triglycerides (TG) and low-density lipoprotein (LDL), with peak reduction of up to 82% in TG and up to 81% in LDL, with a well-tolerated safety profile; presentation anticipated at a medical meeting in the second half of 2025- Story Continues Mean % Change from Baseline at Day 30 post-infusion (+/- SEM) Dose Level (DL) DL1 + DL2 0.1 + 0.3 mg/kg (n=6) DL3 0.6 mg/kg (n=3) DL4 0.8 mg/kg (n=1) Patient type HeFH (4), MDL, sHTG MDL (2), HeFH sHTG Triglycerides -10.6% ± 13.1% -55.7% ± 8.0% -81.9% LDL 34.8% ± 27.0% -28.5% ± 24.4% -64.6% Compelling individual patient responses highlight the therapeutic potential of CTX310: a DL4 patient with sHTG had an 82% reduction in triglycerides from a baseline of 1073 mg/dL at day 30, and a DL3 patient with HeFH had an 81% reduction in LDL-C from a baseline of 256 mg/dL at day 90 – supporting the potential for targeted efficacy in high-risk populations. These initial results represent a significant milestone in the advancement of CRISPR Therapeutics' proprietary lipid nanoparticle (LNP) delivery technologies for gene editing in the liver. The Company plans to present the CTX310 Phase 1 data at a medical meeting in the second half of 2025. CTX320 is in an ongoing Phase 1 clinical trial targeting the LPA gene in patients with elevated lipoprotein(a) [Lp(a)], a genetically determined risk factor associated with increased incidence of major adverse cardiovascular events (MACE). Elevated Lp(a) levels are prevalent in up to 20% of the global population. Dose escalation is ongoing, with an update expected in the second quarter of 2025. CRISPR Therapeutics continues to advance two preclinical programs: CTX340™, targeting angiotensinogen (AGT) for the treatment of refractory hypertension, and CTX450™, targeting 5' aminolevulinic acid synthase 1 (ALAS1) for the treatment of acute hepatic porphyrias (AHP). Both candidates are currently in IND/CTA-enabling studies. Hemoglobinopathies and CASGEVY® (exagamglogene autotemcel [exa-cel]) CASGEVY is approved in the U.S., Great Britain, the EU, the Kingdom of Saudi Arabia (KSA), the Kingdom of Bahrain (Bahrain), Canada, Switzerland and the United Arab Emirates (UAE) for the treatment of both SCD and TDT, and launches are ongoing. Building on the foundational launch in 2024, significant progress is being made to bring this transformative therapy to patients worldwide. As of May 1, more than 65 authorized treatment centers (ATCs) have been activated globally and approximately 90 patients have had their first cell collection. The number of new patients initiating cell collection is expected to grow significantly throughout 2025. Vertex has secured a formal reimbursement agreement with NHS England, enabling access to CASGEVY for patients with SCD. This follows an earlier agreement, reaching in August 2024, providing access for eligible patients with TDT. A similar reimbursement agreement has been established in Wales for eligible SCD and TDT patients. Following a positive assessment, national reimbursement was finalized in Austria. In the Middle East, reimbursement was also finalized across the majority of Emirates, following regulatory approval in the UAE. A manufacturing license application has been submitted to the U.S. Food and Drug Administration (FDA), with commercial production in Portsmouth, New Hampshire expected to begin in the second half of 2025. This submission is part of the planned ramp-up of CASGEVY manufacturing capacity as demand for the therapy increases. CRISPR Therapeutics continues to advance its next-generation approaches designed to significantly broaden the addressable patient population for SCD and TDT. The Company's internally developed targeted conditioning program, an anti-CD117 (c-Kit) antibody-drug conjugate (ADC), remains on track in preclinical development. In parallel, the Company is making continued progress in its in vivo editing platform aimed at enabling direct editing of hematopoietic stem cells (HSC) without the need for conditioning. By potentially eliminating the need for conditioning, this approach could unlock access to transformative therapies for a significantly larger patient population. Immuno-Oncology and Autoimmune Disease Programs Clinical trials are ongoing for its next-generation allogeneic CAR T product candidates, CTX112™ and CTX131™, targeting CD19 and CD70, respectively, across multiple indications. Both candidates incorporate novel potency edits which can lead to significantly higher CAR T cell expansion and cytotoxicity, potentially establishing them as best-in-class allogeneic CAR T products for their respective targets. CTX112 is being developed for hematologic malignancies and autoimmune diseases and has the potential to be best-in-class based on preliminary data. Encouraging clinical data from the ongoing Phase 1/2 clinical trial of CTX112 in relapsed or refractory B-cell malignancies supported the FDA's decision to grant Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of relapsed or refractory follicular lymphoma and marginal zone lymphoma. CTX112 is also in an ongoing Phase 1 clinical trial in autoimmune diseases, including indications such as systemic lupus erythematosus (SLE), systemic sclerosis and inflammatory myositis. Preliminary safety, pharmacokinetic, and pharmacodynamic data from oncology trials support its potential in autoimmune indications. The Company plans to provide an update for both oncology and autoimmune disease in mid-2025. Clinical trials for CTX131™ are ongoing in both solid tumors and hematologic malignancies, with updates expected in 2025. In parallel, an Investigational New Drug (IND) application for glypican-3 (GPC3)-targeted gene-edited autologous CAR T program for the treatment of hepatocellular carcinoma has been opened by our partner, Roswell Park Comprehensive Cancer Center. CRISPR Therapeutics' immuno-oncology and autoimmune disease efforts are supported by a wholly-owned, U.S. manufacturing facility located in Framingham, MA. This investment enables the production of clinical and commercial-stage good manufacturing practice (GMP) materials across the Company's allogeneic cell therapy programs. Regenerative Medicine Programs CRISPR Therapeutics continues to advance its regenerative medicine efforts in Type 1 diabetes (T1D). In addition to CTX211, the Company continues to advance next-generation programs focusing on induced pluripotent stem cell (iPSC) derived, allogeneic, gene-edited, beta islet cell precursors. These approaches aim to achieve insulin independence in T1D patients without the need for chronic immunosuppression. The Company expects to provide an update in 2025. Upcoming Events The Company will participate in the following events in May: 3rd Annual H.C. Wainwright BioConnect Investor Conference, May 20 2025 RBC Capital Markets Global Healthcare Conference, May 20 First Quarter 2025 Financial Results Cash Position: Cash, cash equivalents, and marketable securities were $1,855.3 million as of March 31, 2025, compared to $1,903.8 million as of December 31, 2024. The decrease in cash was primarily driven by operating expenses, offset by proceeds from interest income and employee option exercises. R&D Expenses: R&D expenses were $72.5 million for the first quarter of 2025, compared to $76.2 million for the first quarter of 2024. The decrease in R&D expense was primarily driven by a decrease in employee-related expenses, including stock-based compensation expenses. G&A Expenses: General and administrative expenses were $19.3 million for the first quarter of 2025, compared to $18.0 million for the first quarter of 2024. Collaboration Expense: Collaboration expense, net, was $57.5 million for the first quarter of 2025, compared to $47.0 million for the first quarter of 2024. The increase in collaboration expense, net, was primarily attributable to costs related to CASGEVY and collaboration expenses related to in vivo HSC editing, offset by CASGEVY product sales. Net Loss: Net loss was $136.0 million for the first quarter of 2025, compared to a net loss of $116.6 million for the first quarter of 2024. About CASGEVY® (exagamglogene autotemcel [exa-cel]) CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient's own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate recurrent vaso-occlusive crises (VOCs) for patients with SCD and transfusion requirements for patients with TDT. CASGEVY is approved for certain indications in multiple jurisdictions for eligible patients. About the CRISPR Collaboration and Vertex CRISPR Therapeutics and Vertex entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CASGEVY represents the first potential treatment to emerge from the joint research program. Under an amended collaboration agreement, Vertex now leads global development, manufacturing, and commercialization of CASGEVY and splits program costs and profits worldwide 60/40 with CRISPR Therapeutics. Vertex is the manufacturer and exclusive license holder of CASGEVY. About CTX112 CTX112 is being developed for both oncology and autoimmune indications. CTX112 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 19, or CD19, which incorporates edits designed to evade the immune system, enhance CAR T potency, and reduce CAR T exhaustion. CTX112 is being investigated in an ongoing clinical trial designed to assess safety and efficacy of the product candidate in adult patients with relapsed or refractory B-cell malignancies who have received at least two prior lines of therapy. In addition, CTX112 is being investigated in an ongoing clinical trial designed to assess the safety and efficacy of the product candidate in adult patients with systemic lupus erythematosus, systemic sclerosis, and inflammatory myositis. About CTX131 CTX131 is being developed for both solid tumors and hematologic malignancies, including T cell lymphomas (TCL). CTX131 is a next-generation, wholly-owned, allogeneic CAR T product candidate targeting Cluster of Differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX131 incorporates edits designed to evade the immune system, prevent fratricide, enhance CAR T potency, and reduce CAR T exhaustion. CTX131 is being investigated in ongoing clinical trials designed to assess the safety and efficacy of the product candidate in adult patients with relapsed or refractory solid tumors and hematologic malignancies, including TCL. About In Vivo Programs CRISPR Therapeutics has established a proprietary lipid nanoparticle (LNP) platform for the delivery of CRISPR/Cas9 to the liver. The Company's in vivo portfolio includes its lead investigational programs, CTX310 (directed towards angiopoietin-related protein 3 (ANGPTL3)) and CTX320 (directed towards LPA, the gene encoding apolipoprotein(a) (apo(a)), a major component of lipoprotein(a) [Lp(a)]). Both are validated therapeutic targets for cardiovascular disease. CTX310 and CTX320 are in ongoing clinical trials in patients with heterozygous familial hypercholesterolemia, homozygous familial hypercholesterolemia, mixed dyslipidemias, or severe hypertriglyceridemia, and in patients with elevated lipoprotein(a), respectively. In addition, the Company's research and preclinical development candidates include CTX340 and CTX450, targeting angiotensinogen (AGT) for refractory hypertension and 5'-aminolevulinate synthase 1 (ALAS1) for acute hepatic porphyria (AHP), respectively. About CTX211 CTX211 is an allogeneic, gene-edited, stem cell-derived investigational therapy for the treatment of type 1 diabetes (T1D), which incorporates gene edits that aim to make cells hypoimmune and enhance cell fitness. This immune-evasive cell replacement therapy is designed to enable patients to produce their own insulin in response to glucose. A Phase 1 clinical trial for CTX211 for the treatment of T1D is ongoing. About CRISPR Therapeutics Since its inception over a decade ago, CRISPR Therapeutics has evolved from a research-stage company advancing gene editing programs into a leader that celebrated the historic approval of the first-ever CRISPR-based therapy. The Company has a diverse portfolio of product candidates across a broad range of disease areas including hemoglobinopathies, oncology, regenerative medicine, cardiovascular, autoimmune, and rare diseases. In 2018, CRISPR Therapeutics advanced the first-ever CRISPR/Cas9 gene-edited therapy into the clinic to investigate the treatment of sickle cell disease and transfusion-dependent beta thalassemia. Beginning in late 2023, CASGEVY® (exagamglogene autotemcel [exa-cel]) was approved in several countries to treat eligible patients with either of these conditions. The Nobel Prize-winning CRISPR technology has revolutionized biomedical research and represents a powerful, clinically validated approach with the potential to create a new class of potentially transformative medicines. To accelerate and expand its efforts, CRISPR Therapeutics has formed strategic partnerships with leading companies including Vertex Pharmaceuticals. CRISPR Therapeutics AG is headquartered in Zug, Switzerland, with its wholly-owned U.S. subsidiary, CRISPR Therapeutics, Inc., and R&D operations based in Boston, Massachusetts and San Francisco, California. To learn more, visit CRISPR THERAPEUTICS® standard character mark and design logo, CTX112™, CTX131™, CTX211™, CTX310™, CTX320™, CTX340™ and CTX450™ are trademarks and registered trademarks of CRISPR Therapeutics AG. CASGEVY® and the CASGEVY logo are registered trademarks of Vertex Pharmaceuticals Incorporated. All other trademarks and registered trademarks are the property of their respective owners. CRISPR Special Note Regarding Forward-Looking Statements Statements contained in this press release regarding matters that are not historical facts are 'forward-looking statements' within the meaning of the Private Securities Litigation Reform Act of 1995. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements made by Dr. Kulkarni in this press release, as well as regarding any or all of the following: (i) CRISPR Therapeutics preclinical studies, clinical trials and pipeline products and programs, including, without limitation, manufacturing capabilities, status of such studies and trials, potential expansion into new indications and expectations regarding data, safety and efficacy generally; (ii) data included in this press release, as well as the ability to use data from ongoing and planned clinical trials for the design and initiation of further clinical trials; (iii) CRISPR Therapeutics strategy, goals, anticipated financial performance and the sufficiency of its cash resources; (iv) plans and expectations for the commercialization of, and anticipated benefits of, CASGEVY, including anticipated patient access to CASGEVY; (v) regulatory submissions and authorizations, including timelines for and expectations regarding additional regulatory agency decisions; (vi) the expected benefits of its collaborations; and (vii) the therapeutic value, development, and commercial potential of gene editing and delivery technologies and therapies, including CRISPR/Cas9. Risks that contribute to the uncertain nature of the forward-looking statements include, without limitation, the risks and uncertainties discussed under the heading 'Risk Factors' in its most recent annual report on Form 10-K and in any other subsequent filings made by CRISPR Therapeutics with the U.S. Securities and Exchange Commission. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date they are made. We disclaim any obligation or undertaking to update or revise any forward-looking statements contained in this press release, other than to the extent required by law. This press release also contains information regarding our industry, our business and the markets for certain of our product candidates, including data regarding the estimated size of those markets, and the incidence and prevalence of certain medical conditions. Unless otherwise expressly stated, we obtained this industry, business, market and other data from market research firms and other third parties, including medical publications, government data and similar sources. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events or circumstances may differ materially from events and circumstances reflected in this information. This press release discusses CRISPR/Cas9 gene editing investigational therapies and is not intended to convey conclusions about efficacy or safety as to those investigational therapies or uses of such investigational therapies. There is no guarantee that any investigational therapy will successfully complete clinical development or gain approval from applicable regulatory authorities. Investor Contact: +1-617-307-7503 ir@ Media Contact: +1-617-315-4493 media@ CRISPR Therapeutics AG Condensed Consolidated Statements of Operations (Unaudited, In thousands except share data and per share data) Three Months Ended March 31, 2025 2024 Revenue: Collaboration revenue $ — $ — Grant revenue 865 504 Total revenue $ 865 504 Operating expenses: Research and development 72,484 76,172 General and administrative 19,296 17,953 Collaboration expense, net 57,509 46,966 Total operating expenses 149,289 141,091 Loss from operations (148,424 ) (140,587 ) Total other income, net 13,537 24,720 Net loss before income taxes (134,887 ) (115,867 ) Provision for income taxes (1,109 ) (724 ) Net loss (135,996 ) (116,591 ) Foreign currency translation adjustment 41 (11 ) Unrealized gain (loss) on marketable securities 2,254 (3,454 ) Comprehensive loss $ (133,701 ) $ (120,056 ) Net loss per common share — basic $ (1.58 ) $ (1.43 ) Basic weighted-average common shares outstanding 85,938,720 81,794,630 Net loss per common share — diluted $ (1.58 ) $ (1.43 ) Diluted weighted-average common shares outstanding 85,938,720 81,794,630 CRISPR Therapeutics AG Condensed Consolidated Balance Sheets Data (Unaudited, in thousands) As of March 31, 2025 December 31, 2024 Cash and cash equivalents $ 235,184 $ 298,257 Marketable securities 1,620,101 1,605,569 Working capital 1,748,164 1,849,350 Total assets 2,166,102 2,242,034 Total shareholders' equity 1,829,160 1,932,080
Time of India
23-04-2025
- Business
- Time of India
Lupin diagnostic arm obtains NABL accreditation for all greenfield sites
Mumbai: Indian generics drug maker, Lupin wholly owned diagnostic arm Lupin Diagnostics Limited (LDL) has obtained NABL (National Accreditation Board for Testing and Calibration Laboratories) accreditation for all its greenfield labs. Currently, the diagnostic company operates 27 greenfield labs across the country. 'This accreditation is a testament to the team's dedication to patient care and our mission to promote healthier lives by enhancing healthcare through continuous improvement and innovation,' Ravindra Kumar, CEO, Lupin Diagnostics, commented.
Irish Daily Mirror
22-04-2025
- Health
- Irish Daily Mirror
Tasty fruit can actively help lower your high cholesterol
A delicious fruit that's a hit with many can also actively lower your cholesterol. Packed with nutrients and a specific type of insoluble fibre, this unusual fruit has been linked to cardiovascular benefits in numerous studies. It's important to note that not all fats are harmful when it comes to cholesterol, and certain 'healthy' fats can actually reduce 'bad' cholesterol in the body. Cholesterol naturally exists in our bodies, found in the blood, and works to keep our cells healthy. However, there are 'good' and 'bad' types of cholesterol. 'Bad' cholesterol, also known as low-density lipoprotein (LDL), can lead to serious health problems such as heart disease or put you at risk of a stroke. Conversely, high-density lipoprotein (HDL) cholesterol is referred to as 'good' cholesterol because it 'mops up' LDL from the walls of the body's arteries. This means that higher levels of HDL are generally considered beneficial for heart health - and some foods can help increase HDL in the body. One versatile fatty fruit, the avocado, contains phytosterols, monounsaturated fats and several types of fibre - and research indicates it could be useful in reducing LDL cholesterol, reports Surrey Live. HEART UK , the Cholesterol Charity has highlighted the cholesterol-busting properties of avocados in a recent web post about 'six cholesterol-busting foods'. The charity advises that "cutting down on saturated fat" and substituting some of it with unsaturated fats is "a great way to lower your cholesterol". Alongside avocados, vegetable oils, oily fish, seeds and nuts are all excellent sources of 'good' fats. The Cholesterol charity states: "There are several foods which are not just part of a healthy diet, they can actively help to lower your cholesterol too. Try to eat some of these every day as part of your healthy diet. The more you add them to what you eat, the more they can help lower your cholesterol, especially if you cut down on saturated fat as well." Healthline also shared an article on 'Foods That May Increase Your 'Good Cholesterol' or HDL', explaining the science behind consuming certain foods. Healthline reported that "foods like olive oil, avocado, seeds, and nuts may reduce levels of LDL (bad) cholesterol, thereby improving the percentage of HDL (good) cholesterol in the blood". Healthline further explained how HDL cholesterol aids in removing LDL cholesterol from arteries in the human body. The LDL ('bad' cholesterol) is transported to the liver for processing, effectively removing this cholesterol from the bloodstream. Healthline's website post delved into it: "Eating certain foods cannot directly increase HDL levels because food doesn't contain HDL cholesterol. However, making healthy food choices could affect the way your body metabolizes cholesterol. For instance, it could help lower LDL and raise HDL, thereby improving the HDL to LDL cholesterol ratio in your body." Adding to the findings, the Journal of the Academy of Nutrition and Dietetics noted: "The results of the meta-analysis suggest that avocado consumption may reduce TC (total cholesterol) and LDL-C (low-density lipoprotein cholesterol) in people with elevated baseline LDL-C, without negatively impacting body weight." Despite this, the research posted on Science Direct comes with a proviso – the "certainty of these findings" was branded as "low". The report went on to add that additional research is essential "to better understand the effects of avocados on cardiometabolic health".
