Category: Science

Manifold-Mounted and Inline Direct Acting Valves Offer a Qualified, Cross-Application Solution to the Commercial Space Market

 

MONTVILLE, N.J. — (BUSINESS WIRE) — #additivemanufacturing–Today, Marotta Controls, a rapidly growing aerospace and defense supplier with a 65-year-plus heritage in spaceflight, announced that its latest direct acting solenoid valve is qualified for use in high pressure oxygen systems. Notably, the valve is also suitable for launch vehicle inert gas systems given its high flow capacity, smaller size, rapid response time, and overall cost-effectiveness. The manifold-mounted PLV405 can be configured with two or three ports and is proven to be reusable with a tested high lifecycle count.

Offering the same performance advantages, Marotta Controls also produces an inline model – the MV405. This valve is also available in 2-way or 3-way port configurations.

 

The PLV405 valves offer notable improvements over similar incumbent options, to include nearly double the flow capacity in a 7% lighter package with a 33% faster response time. They are constructed with alloys produced to the ATSM A36 standard.

 

“We understand the complexity of building and qualifying space vehicles. And we understand the importance of simplifying that process any way possible to speed manufacturing without compromising quality,” said Brian Ippolitto, Director, Aerospace Systems Engineering, Marotta Controls. “We view ourselves as more than just suppliers. We operate as true partners who aim to alleviate or at least minimize challenges wherever possible across the whole development cycle. Today, that intention manifests as producing a single, high performing valve with immense versatility.”

 

The 3-way valve is also available in a modified version that supports only Nitrogen, Helium and Air (no Oxygen).

 

The devices are qualified to the Air Force Space Command’s (AFSC) SMC-S-016 standard and are put through Marotta’s advanced cleaning and testing processes used for all space-bound hardware.

 

For more information, visit marotta.com.

 

About Marotta Controls

Founded in 1943, Marotta Controls is a fully-integrated solutions provider which designs, develops, qualifies and manufactures innovative systems and sub-systems for the aerospace and defense sectors. Our portfolio includes pressure, power, motion, fluid, and electronic controls for tactical systems, shipboard and sub-sea applications, satellites, launch vehicles, and aircraft systems. With over 200 patents, Marotta Controls continues to build on its legacy as a highly respected, family-owned small business based in the state of New Jersey. Twitter: @marottacontrols LinkedIn: Marotta Controls, Inc.

Contacts

Heather Ailara

211 Communications

+1.973.567.6040

heather@211comms.com

Katee Glass

Marotta Controls, Inc.

kglass@marotta.com

MORRISTOWN, N.J. — (BUSINESS WIRE) — Melinta Therapeutics, LLC (“Melinta”), a commercial-stage company providing innovative therapies for acute and life-threatening illnesses, announced today that it has acquired the U.S. rights to TOPROL-XL^® (metoprolol succinate) and its Authorized Generic (AG) through an agreement between Melinta and New American Therapeutics Inc.

 

TOPROL-XL^®, approved by the FDA in 1992, is a cardioselective beta-blocker indicated for the treatment of hypertension, alone or in combination with other antihypertensives; the long-term treatment of angina pectoris; and the treatment of stable, symptomatic (NYHA class II or III) heart failure of specific origins.

 

Said Christine Ann Miller, President and Chief Executive Officer, Melinta Therapeutics, “This acquisition immediately expands and diversifies our existing portfolio and serves as fuel for accelerating our long-term growth strategy and enhancing our profitability. We will continue to aggressively pursue portfolio expansion that aligns with our mission of providing innovative therapies for acute and life-threatening illnesses.”

 

“We are extremely proud of our work to provide access to this lifesaving medication,” said Michael Anderson, CEO, New American Therapeutics. “Melinta shares this same commitment to patient access. And they demonstrate that commitment through an impressive supply chain and distribution network that ensures this medication will continue to be available for those patients who need it.”

 

Melinta has begun the integration process to bring TOPROL-XL^® into the company’s existing production, distribution and commercialization structure to ensure this important medication will continue to be made available without interruption.

 

Terms of the transaction were not disclosed.

 

About Melinta Therapeutics

Melinta Therapeutics, LLC provides innovative therapies to people impacted by acute and life-threatening illnesses. Our portfolio currently includes five commercial-stage antibiotics: BAXDELA^® (delafloxacin), KIMYRSA™ (oritavancin), MINOCIN^® (minocycline) for Injection, ORBACTIV^® (oritavancin), and VABOMERE^® (meropenem and vaborbactam) and a commercial-stage cardiovascular product: TOPROL-XL^® (metoprolol succinate). With an unsurpassed commitment to providers and the patients they serve, we work to ensure that all people who need our therapies can receive them. We focus our expanding portfolio on serving patients with an unmet need because that’s how we make the most meaningful impact. At Melinta, we’re visionaries dedicated to innovation while staying grounded in what matters most: patients. Visit www.melinta.com for more information.

 

TOPROL-XL^® is a registered trademark of AstraZeneca Pharmaceuticals LP and is used with permission.

 

About TOPROL-XL® (metoprolol succinate)

TOPROL-XL® is a beta-adrenergic blocker indicated for the treatment of:

• Hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions
• Angina Pectoris
• Heart Failure, to reduce the risk of cardiovascular mortality and heart failure hospitalizations in patients with heart failure

 

IMPORTANT SAFETY INFORMATION

Contraindications

• Known hypersensitivity to product components.
• Severe bradycardia: Greater than first degree heart block, or sick sinus syndrome without a pacemaker.
• Cardiogenic shock or decompensated heart failure.

 

Warnings and Precautions

• Abrupt cessation may exacerbate angina pectoris or myocardial ischemia. Reduce dosage gradually over a period of 1 to 2 weeks and monitor the patient. Warn patients not to discontinue without their physician’s advice.
• Heart Failure: Worsening cardiac failure may occur during up-titration.
• Bronchospastic Disease: Avoid beta blockers.
• Bradycardia, including sinus pause, heart block, and cardiac arrest have occurred with the use of TOPROL-XL. Patients with first-degree atrioventricular block, sinus node dysfunction, conduction disorders (including Wolff- Parkinson-White) or on concomitant drugs that cause bradycardia (digitalis glycosides, clonidine, and diltiazem and verapamil) may be at increased risk. Monitor heart rate.
• Pheochromocytoma: Initiate therapy with an alpha blocker.
• Major Surgery: Avoid initiation of high-dose extended-release metoprolol in patients undergoing noncardiac surgery. Do not routinely withdraw chronic beta blocker therapy prior to surgery.
• Diabetes and Hypoglycemia: May mask tachycardia occurring with hypoglycemia.
• Thyrotoxicosis: Abrupt withdrawal in patients with thyrotoxicosis might precipitate a thyroid storm.
• Peripheral Vascular Disease: Can precipitate or aggravate symptoms of arterial insufficiency.
• Patients may be unresponsive to the usual doses of epinephrine used to treat an allergic reaction.

 

Adverse Reactions

Most common adverse reactions: tiredness, dizziness, depression, shortness of breath, bradycardia, hypotension, diarrhea, pruritus, rash.

Contacts

Susan Blum

Chief Financial Officer

Melinta Therapeutics, LLC

908-617-1300

info@melinta.com

• Late-breaking data from prespecified subgroup analyses of FIDELITY evaluate KERENDIA^® (finerenone) on cardiovascular (CV) and kidney outcomes, including patients with stages 1-4 chronic kidney disease (CKD) associated with type 2 diabetes (T2D), with or without a history of atherosclerotic cardiovascular disease¹
• FIDELITY, a prespecified exploratory pooled analysis of the FIDELIO-DKD and FIGARO-DKD studies, comprises the largest Phase III cardiorenal outcomes clinical trial program to evaluate the risk of progression of kidney disease as well as fatal and nonfatal CV events in >13,000 patients with CKD associated with T2D^1,2

 

WHIPPANY, N.J. — (BUSINESS WIRE) — Bayer announced today late-breaking data from prespecified exploratory subgroup analyses of FIDELITY, a prespecified pooled analysis of the Phase III FIDELIO-DKD and FIGARO-DKD trials. These analyses investigated KERENDIA^® (finerenone) versus placebo on composite cardiovascular (CV) and kidney outcomes in patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D), with and without a history of atherosclerotic cardiovascular disease (ASCVD).¹ The subgroup analyses were presented today at the American College of Cardiology’s 71st Annual Scientific Session (ACC.22).

Out of the 13,026 patients included in the FIDELITY full analysis, 5935 (45.6%) had a history of ASCVD at baseline.¹ Over a median follow-up of 3 years, patients with ASCVD versus those without had the following composite CV outcome of time to CV death, nonfatal myocardial infarction (MI), nonfatal stroke and hospitalization for heart failure (HHF; incident rate [IR]/100 patient-years [PY] 6.9 vs. 3.0; hazard ratio [HR] 2.09; 95% confidence interval [CI] 1.89–2.30), composite outcome of time to CV death or HHF (IR/100 PY, 4.51 vs. 1.92; HR: 2.12; 95% CI 1.88–2.40) and composite kidney outcome (IR/100 PY 2.1 vs. 2.4; HR: 0.96; 95% CI 0.83–1.10).¹

 

KERENDIA was approved in the United States on July 9, 2021, based on the results of FIDELIO-DKD, to reduce the risk of sustained estimated glomerular filtration rate (eGFR) decline, end-stage kidney disease, CV death, nonfatal MI and HHF in adult patients with CKD associated with T2D.³ The KERENDIA label contains a Warning and Precaution that KERENDIA can cause hyperkalemia.³ For more information, see “Important Safety Information” and the FIDELIO-DKD study results below.

 

The prespecified exploratory subgroup analyses of FIDELITY showed that the treatment effect of finerenone, when compared to placebo, was consistent in patients with or without history of ASCVD for the composite CV outcome of time to CV death, nonfatal MI, nonfatal stroke or HHF (HR: 0.83; 95% CI 0.74–0.94; HR: 0.91; 95% CI 0.78–1.06; P-value for interaction=0.38, respectively). The treatment effect, when compared to placebo, was also consistent in patients with or without history of ASCVD for the composite outcome of CV death or HHF (HR: 0.82; 95% CI 0.71–0.94; HR: 0.86; 95% CI 0.71–1.04; P-value for interaction: 0.68, respectively).¹

 

Regarding the effects of finerenone on the composite kidney outcome of time to kidney failure, sustained ≥57% decrease in eGFR or kidney-related death, the treatment effect was consistent in patients with or without a history of ASCVD (HR: 0.71; 95% CI 0.57–0.88; HR: 0.81; 95% CI 0.68–0.97; P-value for interaction: 0.33, respectively).¹

 

“In patients with chronic kidney disease associated with type 2 diabetes, cardiovascular complications are among the most frequent causes of death.^4,5 However, there is limited data on how the risk of cardiovascular events could be reduced in these patients,” said Javed Butler, MD, MPH, MBA, president of the Baylor Scott & White Research Institute and senior vice president for Baylor Scott & White Health, and distinguished professor of medicine at the University of Mississippi. “These subgroup analyses investigate outcomes in patients suffering from chronic kidney disease associated with type 2 diabetes, with or without a history of atherosclerotic cardiovascular disease. The analyses show us that in both cases, there’s a need to treat patients irrespective of where they are on the atherosclerotic cardiovascular disease spectrum.”

 

“Patients with chronic kidney disease and type 2 diabetes are three times more likely to die from a cardiovascular event than those with type 2 diabetes alone.⁶ That said, the severity of kidney impairment correlates with a higher incidence of cardiovascular events,” said Dr. Christian Rommel, member of the executive committee of Bayer AG’s pharmaceutical division and head of research and development.⁵ “The latest prespecified subgroup analyses of FIDELITY add to our growing body of data on the renal and CV outcomes of finerenone in adults with chronic kidney disease associated with type 2 diabetes.”

 

About KERENDIA (finerenone)

INDICATION:

• KERENDIA is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, nonfatal myocardial infarction, and hospitalization for heart failure in adult patients with chronic kidney disease (CKD) associated with type 2 diabetes (T2D)³

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS:

• Concomitant use with strong CYP3A4 inhibitors³
• Patients with adrenal insufficiency³

WARNINGS AND PRECAUTIONS:

• Hyperkalemia: KERENDIA can cause hyperkalemia. The risk for developing hyperkalemia increases with decreasing kidney function and is greater in patients with higher baseline potassium levels or other risk factors for hyperkalemia. Measure serum potassium and eGFR in all patients before initiation of treatment with KERENDIA and dose accordingly. Do not initiate KERENDIA if serum potassium is >5.0 mEq/L³

  Measure serum potassium periodically during treatment with KERENDIA and adjust dose accordingly. More frequent monitoring may be necessary for patients at risk for hyperkalemia, including those on concomitant medications that impair potassium excretion or increase serum potassium³

MOST COMMON ADVERSE REACTIONS:

• Adverse reactions reported in ≥1% of patients on KERENDIA and more frequently than placebo: hyperkalemia (18.3% vs. 9%), hypotension (4.8% vs. 3.4%), and hyponatremia (1.4% vs. 0.7%)³

DRUG INTERACTIONS:

• Strong CYP3A4 Inhibitors: Concomitant use of KERENDIA with strong CYP3A4 inhibitors is contraindicated. Avoid concomitant intake of grapefruit or grapefruit juice³
• Moderate and Weak CYP3A4 Inhibitors: Monitor serum potassium during drug initiation or dosage adjustment of either KERENDIA or the moderate or weak CYP3A4 inhibitor and adjust KERENDIA dosage as appropriate³
• Strong and Moderate CYP3A4 Inducers: Avoid concomitant use of KERENDIA with strong or moderate CYP3A4 inducers³

USE IN SPECIFIC POPULATIONS:

• Lactation: Avoid breastfeeding during treatment with KERENDIA and for 1 day after treatment³
• Hepatic Impairment: Avoid use of KERENDIA in patients with severe hepatic impairment (Child Pugh C) and consider additional serum potassium monitoring with moderate hepatic impairment (Child Pugh B)³

Please read the Prescribing Information for KERENDIA.

About Finerenone Phase III Clinical Trials Program

Having randomized more than 13,000 patients with CKD associated with T2D around the world, the Phase III program with finerenone in CKD associated with T2D comprises two studies, evaluating the effect of finerenone versus placebo on top of standard of care (SoC) on both renal and CV outcomes.⁷

The FIDELIO-DKD (FInerenone in reducing kiDnEy faiLure and dIsease prOgression in Diabetic Kidney Disease) study was a randomized, double-blind, placebo-controlled, multicenter study in adult patients with CKD associated with T2D, defined as either having an uACR of 30 to 300 mg/g, eGFR 25 to 60 mL/min/1.73 m² and diabetic retinopathy, or as having an uACR of ≥300 mg/g and an eGFR of 25 to 75 mL/min/1.73 m².^3,8 The trial excluded patients with known significant nondiabetic kidney disease and a clinical diagnosis of chronic heart failure with reduced ejection fraction and persistent symptoms (NYHA class II to IV).³ All patients were to have a serum potassium ≤4.8 mEq/L at screening and be receiving standard of care background therapy, including a maximum tolerated labeled dose of an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB).³ A total of 5,674 patients were randomized to receive finerenone (N=2,833) or placebo (N=2,841) and were followed for a median of 2.6 years.³ The mean age of the study population was 66 years, and 70% of patients were male.³ The trial population was 63% white, 25% Asian, and 5% Black.³

Finerenone reduced the incidence of the primary composite endpoint of a sustained decline in eGFR of ≥40%, kidney failure, or renal death (HR 0.82 [95% CI, 0.73-0.93; P=0.001]).³ The treatment effect reflected a reduction in a sustained decline in eGFR of ≥40% and progression to kidney failure.³ There were few renal deaths during the trial.³

Finerenone also reduced the incidence of the composite endpoint of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for heart failure (HR 0.86 [95% CI, 0.75-0.99; P=0.034]).³ The treatment effect reflected a reduction in cardiovascular death, nonfatal myocardial infarction and hospitalization for heart failure.³

The most frequently reported adverse reaction was hyperkalemia (18.3% KERENDIA vs. 9% placebo).³ Hospitalization due to hyperkalemia for the KERENDIA group was 1.4% versus 0.3% in the placebo group.³ Hyperkalemia led to permanent discontinuation of treatment in 2.3% of patients receiving KERENDIA versus 0.9% of patients receiving placebo.³

FIGARO-DKD (FInerenone in reducinG cArdiovascular moRtality and mOrbidity in Diabetic Kidney Disease), a randomized, double-blind, placebo-controlled trial, randomly assigned 7,352 participants to finerenone (N=3686) or placebo (N=3666) on top of standard of care, including a maximum tolerated labeled dose of ACEis or ARBs.⁹ Patients had UACR ≥30–<300 mg/g and eGFR ≥25–≤90 mL/min/1.73m² or UACR ≥300–≤5000 mg/g and eGFR ≥60 mL/min/1.73m².⁹ This data is under review with the FDA.

KERENDIA significantly reduced the risk of the composite primary endpoint of time to first occurrence of CV death or nonfatal CV events (myocardial infarction, stroke or heart failure hospitalization) by 13% (relative risk reduction, HR 0.87 [95% CI, 0.76-0.98; P=0.0264]) over a median duration of follow-up of 3.4 years when added to maximum tolerated labeled dose of ACEi or ARB in adults with CKD associated with T2D.⁹ The reduction in the CV composite outcome was primarily driven by hospitalization due to heart failure.⁹

The incidence of the secondary endpoint, a composite of time to kidney failure, a sustained decrease of eGFR ≥40% from baseline over a period of at least four weeks, or renal death, was lower with finerenone than with placebo, affecting 350 (9.5%) and 395 (10.8%) patients, respectively.⁹ However, the difference was not statistically significant (HR 0.87 [95% CI, 0.76-1.01; P=0.0689]) over a median duration of follow-up of 3.4 years.⁹

Overall, hyperkalemia-related adverse events occurred more often in patients receiving finerenone compared with placebo (10.8% and 5.3%, respectively).⁹ Hospitalization due to hyperkalemia for the finerenone group was 0.6% versus <0.1% in the placebo group, and there was no hyperkalemia-related death in either treatment group. Treatment was discontinued due to hyperkalemia in 1.2% of patients treated with finerenone compared to 0.4% in the placebo group.⁹

Bayer also recently announced the initiation of the FINEARTS-HF study, a multicenter, randomized, double-blind, placebo-controlled Phase III study that will investigate finerenone compared to placebo in more than 5,500 symptomatic heart failure patients (NYHA class II-IV) with a left ventricular ejection fraction of ≥40%.¹⁰ The primary objective of the study is to demonstrate superiority of finerenone over placebo in reducing the rate of the composite endpoint of cardiovascular death and total (first and recurrent) heart failure events (defined as hospitalizations for heart failure or urgent heart failure visits).¹⁰

About Chronic Kidney Disease Associated With Type 2 Diabetes

Patients with CKD associated with T2D are three times more likely to die from a CV-related cause than those with T2D alone.⁶ CKD is a serious and progressive condition that is generally underrecognized.¹¹ CKD is a frequent complication arising from T2D and is also an independent risk factor of CV disease.^12-14 Approximately 40% of all patients with T2D develop CKD.¹⁴ Despite guideline-directed therapies, patients with CKD associated with T2D remain at high risk of CKD progression and CV events.^12,13,15,16 T2D is the leading cause of end-stage kidney disease, which requires dialysis or a kidney transplant to stay alive.^17-19

About Bayer’s Commitment in Cardiovascular and Kidney Diseases

Bayer is an innovation leader in the area of cardiovascular diseases, with a long-standing commitment to delivering science for a better life by advancing a portfolio of innovative treatments. The heart and the kidneys are closely linked in health and disease, and Bayer is working in a wide range of therapeutic areas on new treatment approaches for cardiovascular and kidney diseases with high unmet medical needs. The cardiology franchise at Bayer already includes a number of products and several other compounds in various stages of preclinical and clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cardiovascular diseases are treated.

About Bayer

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, go to www.bayer.com.

Find more information at www.pharma.bayer.com
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Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References

1. Filippatos G, et al. Finerenone and cardiorenal outcomes by history of cardiovascular disease in patients with type 2 diabetes and chronic kidney disease: FIDELITY analyses. Oral presentation at: ACC.22. April 4, 2022. Washington, D.C. https://www.abstractsonline.com/pp8/#!/10461/presentation/22134
2. Agarwal R, Filippatos G, Pitt B, et al. Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis. Eur Heart J. 2022;43(6):474-484.
3. KERENDIA (finerenone) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; July 2021.
4. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17:83.
5. Fox CS, Matsushita K, Woodward M, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis [published correction appears in Lancet. 2013 Feb 2;381(9864):374]. Lancet. 2012;380(9854):1662-1673.
6. Afkarian M, Sachs MC, Kestenbaum B, et al. Kidney disease and increased mortality risk in type 2 diabetes. J Am Soc Nephrol. 2013;24(2):302-308..
7. Ruilope LM, et al. Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial. Am J Nephrol. 2019;50(5)345-356.
8. Bakris G, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020. 2020;383:2219-2229.
9. Pitt B, et al. Cardiovascular events with finerenone in kidney disease and type 2 diabetes. N Engl J Med. 2021;10.1056/NEJMoa2110956. doi:10.1056/NEJMoa2110956.
10. ClinicalTrials.gov. Study to Evaluate the Efficacy (Effect on Disease) and Safety of Finerenone on Morbidity & Mortality in Participants with Heart Failure and Left Ventricular Ejection Fraction Greater or Equal to 40% (FINEARTS-HF). 2020. Accessed November 2021. https://clinicaltrials.gov/ct2/show/NCT04435626
11. Breyer MD, et al. Developing treatments for chronic kidney disease in the 21st Century. Semin Nephrol. 2016. 2016;36(6):436-447.
12. Anders HJ, et al. CKD in diabetes: diabetic kidney disease versus nondiabetic kidney disease. Nat Rev Nephrol. 2018;14:361-377.
13. Thomas MC, et al. Diabetic kidney disease. Nat Rev Dis Primers. 2015;1:1-20.
14. Bailey R, et al. Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging. BMC Res Notes. 2014;7(1):415. doi:10.1186/1756-0500-7-415.
15. KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2013;3:1-150.
16. American Diabetes Association standards of medical care in diabetes – 2021. Diabetes Care. 2021;44(1):1-244.
17. National diabetes statistics report 2020: estimates of diabetes and its burden in the United States. Centers for Disease Control and Prevention. Accessed July 9, 2021. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
18. Stages of CKD. American Kidney Fund. Accessed May 11, 2021. https://www.kidneyfund.org/kidney-disease/chronic-kidney-disease-ckd/stages-of-chronic-kidney-disease/
19. United States Renal Data System. USRDS Annual data report. Volume 1: Chronic kidney disease. Chapter 6: Healthcare expenditures for persons with CKD. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. 2020. Accessed November 2021. https://adr.usrds.org/2020/chronic-kidney-disease/6-healthcare-expenditures-for-persons-with-ckd

Contacts

Media:

Elaine Colón

Tel. +1 732-236-1587

Email: elaine.colon@bayer.com

WARREN, N.J. — (BUSINESS WIRE) — #CD8—Tevogen Bio, a clinical stage biotechnology company developing cell and gene therapies in virology, oncology, and neurology, recently announced it has completed a strategic investment by HMP Partners of New Jersey, a life sciences investment firm managed by medical doctors.

Tevogen’s next generation precision T cell platform is designed to provide increased target specificity to eliminate malignant and viral infected cells, while allowing healthy cells to remain intact. Multiple targets are selected in advance with the goal of overcoming mutational capacity of cancer cells and viruses. The potentially disruptive technology is designed to allow development of unmodified T cell therapeutics from a single donor to treat hundreds of patients sharing the same human leukocyte antigen (HLA) type, without the need for specialized medical facilities. Tevogen believes that this “off-the-shelf” convenience will make it possible to develop T cell therapies with greater convenience, unprecedented speed, and at a much lower cost than currently available platforms, such as CAR-T. This creates an opportunity to dramatically improve health outcomes for large patient populations battling common life-threatening cancers and viral infections.

 

Tevogen intends to use the net proceeds from the investment to expedite expansion of Tevogen’s development pipeline and to support accelerated development of Tevogen’s lead product candidate. The candidate, TVGN-489, is a COVID-19-specific CD8+ T lymphocyte (CTL) investigational product, currently in proof-of-concept trial that recently passed its midway point. TVGN-489 is a highly purified product designed to detect proteins that are spread across the entire viral genome and found across COVID-19 variants. In addition, TVGN-489 is designed not to be susceptible to spike mutations as the targets are selected from the entire genome.

 

Tevogen believes that therapeutic approaches to date have not harnessed CD8+ Cytotoxic T-Lymphocytes, also known as killer T cells to their full potential for clinical application. Currently available approaches include both genetically unmodified T cells applied to the treatment of viruses early after transplant and genetically modified CAR-T cells used to treat a selected subset of malignancies.

 

Tevogen CEO Ryan Saadi, M.D., M.P.H., said, “We are excited to continue to partner with this exceptional group of investors who, as medical experts, are keenly in tune with what we see as the vast potential of personalized CD8+ Cytotoxic T lymphocytes for therapeutic purposes. The Tevogen team has developed an innovative technology that we believe will enable development of affordable T cell therapies for millions of patients suffering from cancers and viral infections, and we are gratified that HMP Partners has invested again.”

 

“We have experienced how disruptive technologies like Tevogen’s precision T cell platform can bring profound changes to medicine and are impressed by the accomplishments and business acumen Tevogen leadership has shown in a short 18 months,” said Hema Patel, Managing Partner of HMP Partners. “We are excited to make another investment in Tevogen’s ingenuity and are hopeful Tevogen’s novel business model built on bringing life-saving therapies to large patient populations will become the gold standard in the biopharma industry and usher in a new frontier of medicine. We believe Tevogen has significant potential, and based on a discounted cash flow analysis, think the company’s valuation even today could be in excess of $5 billion.”

 

About Tevogen’s Next Generation Precision T Cell Platform

Tevogen’s next generation precision T cell platform is designed to provide increased specificity to eliminate malignant and viral infected cells, while allowing healthy cells to remain intact. Multiple targets are selected in advance with the goal of overcoming mutational capacity of cancer cells and viruses.

 

Tevogen believes its technology has the potential to overcome the primary barriers to the broad application of personalized T cell therapies: potency, purity, production-at-scale, and patient-pairing, without the limitations of current approaches. Tevogen’s goal is to open the vast and unprecedented potential of developing personalized immunotherapies for large patient populations impacted by common cancers and viral infections.

 

About Tevogen Bio

Tevogen Bio is driven by a team of distinguished scientists and highly experienced biopharmaceutical leaders who have successfully developed and commercialized multiple franchises. Tevogen’s leadership believes that accessible personalized immunotherapies are the next frontier of medicine, and that disruptive business models are required to sustain medical innovation in the post-pandemic world.

 

About HMP Partners

HMP Partners of New Jersey is a life-sciences investment fund formed by a consortium of medical doctors who are dedicated to supporting the advancement of potentially life-saving technologies.

 

Forward Looking Statements

This press release contains certain forward-looking statements relating to Tevogen Bio™ Inc (the “Company”) and its business. These statements are based on management’s current expectations and beliefs as of the date of this release and are subject to a number of factors which involve known and unknown risks, delays, uncertainties and other factors not under the Company’s control that may cause actual results, performance or achievements to be materially different from the results, performance or other expectations implied by these forward-looking statements. Forward-looking statements can sometimes be identified by terminology such as “may,” “will,” “should,” “intend,” “expect,” “believe,” “potential,” “possible,” or their negatives or comparable terminology, as well as other words and expressions referencing future events, conditions, or circumstances. In any forward-looking statement in which the Company expresses an expectation or belief as to future results, there can be no assurance that the statement or expectation or belief will be achieved. Various factors may cause differences between the Company’s expectations and actual results, including, among others: the Company’s limited operating history; uncertainties inherent in the execution, cost and completion of preclinical studies and clinical trials; risks related to regulatory review and approval and commercial development; risks associated with intellectual property protection; and risks related to matters that could affect the Company’s future financial results, including the commercial potential, sales, and pricing of the Company’s products. Except as required by law, the Company undertakes no obligation to update the forward-looking statements or any of the information in this release, or provide additional information, and expressly disclaims any and all liability and makes no representations or warranties in connection herewith or with respect to any omissions herefrom.

Contacts

Media Contact:
Katelyn Joyce

Corporate Communications Lead

Katelyn.joyce@tevogen.com

ENGLEWOOD CLIFFS, N.J. — (BUSINESS WIRE) — #CRIOM—Enzychem Lifesciences (KOSDAQ: 183490), a late-stage biotechnology company, announced today that the company has completed the final Clinical Study Report (CSR) for their Phase 2 study of EC-18 in Chemoradiation-induced Oral Mucositis (CRIOM), entitled “Phase 2, multi-center, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of EC-18 in altering the severity and course of oral mucositis (OM) in subjects being treated with concomitant chemoradiation therapy for cancers of the mouth, oropharynx, hypopharynx, and nasopharynx.”

The phase 2 U.S. study was designed as 2 stages with 105 randomized subjects at 21 sites to evaluate the safety, tolerability, and efficacy of its lead compound, EC-18 on mitigating severe oral mucositis (SOM) in head and neck subjects receiving concomitant chemoradiation therapy for cancers of the mouth, oropharynx, hypopharynx, and nasopharynx.

 

An iDSMB evaluated the safety endpoint every two weeks in a blinded fashion, until 30 days after the last dosing of Stage 1. If a safety issue was noted, the iDSMB was instructed to unblind the treatment assignments to ascertain if the adverse event (AE) was associated with the study drug. Since no safety issues were identified at the end of Stage 1, Stage 2 commenced using 2000 mg of the study drug, consistent with a positive safety outcome.

 

The primary efficacy endpoint demonstrated that the median duration of SOM (defined as WHO Grades 3 or 4) from baseline through short-term follow-up period (STFU) was 0.0 days in the EC-18 group versus 13.5 days in the placebo group (100% reduction).

 

The secondary efficacy endpoints showed that the incidence of SOM from baseline through the active treatment period was reduced by 37.1% in the EC-18 group when compared to the placebo group (40.9% vs. 65.0%). Similarly, the incidence of SOM from baseline through the STFU period also reported a reduction by 35.0% in comparison to the placebo group (45.5% vs. 70.0%). Based on the estimated median time to onset of SOM with a confidence interval of 95% utilizing the Kaplan Meier analysis, the time of onset of SOM was 8 days longer in the EC-18 group in comparison to the placebo group (43 days vs. 51 days). Also, EC-18 showed a median delay of 11.5 days in time to the first use of opioid analgesics when compared to the placebo group (37 days vs. 25.5 days).

 

About Enzychem Lifesciences

Enzychem Lifesciences (KOSDAQ: 183490) is a clinical-stage biopharmaceutical company focused on developing oral small molecule therapies for patients with unmet medical needs in oncology, metabolic and inflammatory diseases. EC-18 acts as an immunomodulator, facilitating the resolution of inflammation and early return to homeostasis. Enzychem is headquartered in South Korea, with an office in the United States. For more information, please visit www.enzychem.com.

Contacts

Investors / Business Development

Ted Kim

Director of Business Development

ted.kim@enzychem.com

Media

Sanghyun Lee

Public Relations Associate

noah.lee@enzychem.com

Michael Parrish Named Vice President of Public Affairs, Science and Sustainability in the U.S.

Duane Simpson Named Vice President of North America Crop Science Public Affairs, Science and Sustainability

 

WHIPPANY, N.J. — (BUSINESS WIRE) — Bayer today announced the appointment of Michael Parrish to the position of Vice President of Public Affairs, Science and Sustainability, U.S. Parrish has served as the interim lead of U.S. Public Affairs since April 2021, following the function’s formation. In this new role, he will be responsible for driving a unified organization and strategy, including oversight of the company’s U.S. Government Relations, Policy and Corporate Engagement teams.

To continue to align and unify our efforts with policymakers at the state and federal levels, government relations for Crop Science will now shift to the U.S. Public Affairs, Science and Sustainability team, bringing our three divisional government affairs efforts to one team representing Bayer. In this capacity, the company has promoted Duane Simpson to Vice President of the North America Crop Science Public Affairs, Science and Sustainability Team. Simpson and his team will be responsible for engaging with key federal and state agencies, as well as industry and trade associations, that help govern the technologies that farmers use and support the growth of the U.S. and Canadian agriculture sectors.

 

Parrish will continue to report to Patrick Lockwood-Taylor, President of Bayer U.S., and serve as a member of the U.S. Country Leadership Team, as well as the Global Public Affairs Leadership Team reporting to Matthias Berninger, Senior Vice President, Public Affairs and Sustainability. Simpson will report to Jacqueline Applegate, President, North America Crop Science, and continue to be a part of the Crop Science North American Leadership Team.

 

“As a top U.S. life sciences company, we remain focused on using our science-based innovation for better lives, and leading with heart, to make our vision of ‘Health for All, Hunger for None’ a reality for generations to come,” said Patrick Lockwood-Taylor, President of Bayer U.S. “These appointments recognize the tremendous success both Michael Parrish and Duane Simpson have already brought to Bayer. Under their leadership, the organization will continue to build and strengthen relationships with policymakers and key stakeholders that are essential to advancing our growth and value – and our success – in the company’s most important market.”

 

Parrish brings a wealth of experience to the role, with more than 20 years in government service and government relations in corporate settings, working with elected officials, and various roles held at the U.S. Department of State and Department of Justice. Simpson has nearly 30 years of experience in political campaigns, state government, trade associations, industry affairs and government affairs at both the state and federal level.

 

Parrish and Simpson assume their new responsibilities effective March 1, 2022.

 

Bayer: Science For A Better Life

Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to help people and planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2020, the Group employed around 100,000 people and had sales of 41.4 billion euros. R&D expenses before special items amounted to 4.9 billion euros. For more information, go to www.bayer.us.

 

Bayer U.S. Social Media Channels: Facebook / Twitter / Instagram

Bayer® and the Bayer Cross® are registered trademarks of Bayer.

 

Forward-Looking Statements

This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

Contacts

Nicole Hayes, Bayer U.S.

Nicole.Hayes@bayer.com
201-421-5268

• CARVYKTI™ marks the first product approved by a health authority for Legend Biotech
• Approval is primarily based on the pivotal phase 1b/2 CARTITUDE-1 study, which demonstrated an overall response rate (ORR) of 98 percent in patients with refractory or relapsed multiple myeloma after four or more prior lines of therapy including proteasome inhibitor, immunomodulatory agent and anti-CD38 monoclonal antibody¹

 

SOMERSET, N.J. — (BUSINESS WIRE) — $LEGN–Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, today announced that the U.S. Food and Drug Administration (FDA) has approved its first product, CARVYKTI™ (ciltacabtagene autoleucel; cilta-cel), for the treatment of adults with relapsed or refractory multiple myeloma (RRMM) who have received four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel in December 2017.

CARVYKTI™ is a chimeric antigen receptor T-cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting single domain antibodies and given as a one-time infusion with a recommended dose range of 0.5 to 1.0 x 10⁶ CAR-positive viable T cells per kg of body weight. In the pivotal CARTITUDE-1 study, deep and durable responses were seen in patients with RRMM (n=97), with a high overall response rate (ORR) of 98 percent (95 percent confidence interval [CI]: 92.7-99.7) including 78 percent of the patients achieving stringent complete response (sCR, 95 percent CI: 68.8-86.1).¹ At a median of 18 months follow-up, the median duration of response (DOR) was 21.8 months (95 percent CI 21.8-not estimable).¹

 

CARVYKTI™ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI™ REMS Program.¹ The Safety Information for CARVYKTI™ includes a Boxed Warning regarding Cytokine Release Syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), Parkinsonism and Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), and prolonged and/or recurrent cytopenia.¹ Warnings and Precautions include prolonged and recurrent cytopenias, infections, hypogammaglobulinemia, hypersensitivity reactions, secondary malignancies and effects on ability to drive and use machines.¹ The most common adverse reactions (≥20 percent) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.¹

“Multiple myeloma remains an incurable disease with heavily pretreated patients facing poor prognoses with limited treatment options,” said Ying Huang, PhD, CEO and CFO of Legend Biotech. “Today’s approval of CARVYKTI is a pivotal moment for Legend Biotech because it is our first-ever marketing approval, but what really excites us is the drug’s potential to become an impactful therapy option for patients in need of long, treatment-free intervals. This is the first of many cell therapies we plan to bring to patients as we continue advancing our pipeline across disease states.”

 

Multiple myeloma affects a type of white blood cell called plasma cells, which are found in the bone marrow.² The majority of patients relapse after undergoing initial treatment and face poor prognoses after treatment with three major drug classes, including immunomodulatory agent, a proteasome inhibitor and anti-CD38 monoclonal antibody.^3,4,5

 

“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse with fewer patients achieving a deep response as they progress through later lines of therapy,” said Dr. Sundar Jagannath, MBBS, Professor of Medicine, Hematology and Medical Oncology at Mount Sinai, and principal study investigator. “This is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population. Today’s approval of CARVYKTI helps address a great unmet need for these patients.”

 

As a personalized medicine, CARVYKTI™’s administration requires extensive training, preparation, and certification to ensure a seamless experience for patients. Through a phased approach, Legend and Janssen will activate a limited network of certified treatment centers as they work to scale production capacity and increase the availability of CARVYKTI™ throughout the U.S. in 2022 and beyond, ensuring that the CARVYKTI™ treatment can be provided to oncologists and their patients in a reliable and timely manner.

 

About CARVYKTI™ (Ciltacabtagene autoleucel; cilta-cel)

CARVYKTI™ is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells. The CARVYKTI™ CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.¹

 

In December 2017, Legend Biotech Corporation entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. to develop and commercialize cilta-cel.

 

In April 2021, Legend announced the submission of a Marketing Authorisation Application to the European Medicines Agency seeking approval of cilta-cel for the treatment of patients with relapsed and/or refractory multiple myeloma. In addition to U.S. Breakthrough Therapy Designation granted in December 2019, cilta-cel received a Breakthrough Therapy Designation in China in August 2020. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019, and from the European Commission in February 2020.

About the CARTITUDE-1 Study

CARTITUDE-1 (NCT03548207) is an ongoing Phase 1b/2, open-label, single arm, multi-center trial evaluating cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received at least three prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal antibody.¹

 

The longer-term efficacy and safety profile of cilta-cel is being assessed in the ongoing CARTITUDE-1 study, with two-year follow-up results recently presented at ASH 2021.⁶

 

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.² In 2022, it is estimated that more than 34,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S.⁷ While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.⁸ Although treatment may result in remission, unfortunately, patients will most likely relapse.³ Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.^4,5

 

CARVYKTI™ Important Safety Information

INDICATIONS AND USAGE

CARVYKTI™ (ciltacabtagene autoleucel) is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

 

WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, and PROLONGED and RECURRENT CYTOPENIA

• Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with CARVYKTI™. Do not administer CARVYKTI™ to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), which may be fatal or life-threatening, occurred following treatment with CARVYKTI™, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with CARVYKTI™. Provide supportive care and/or corticosteroids as needed.
• Parkinsonism and Guillain-Barré syndrome and their associated complications resulting in fatal or life-threatening reactions have occurred following treatment with CARVYKTI™.
• Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), including fatal and life-threatening reactions, occurred in patients following treatment with CARVYKTI™. HLH/MAS can occur with CRS or neurologic toxicities.
• Prolonged and/or recurrent cytopenias with bleeding and infection and requirement for stem cell transplantation for hematopoietic recovery occurred following treatment with CARVYKTI™.
• CARVYKTI™ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI™ REMS Program.

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS) including fatal or life-threatening reactions, occurred following treatment with CARVYKTI™ in 95% (92/97) of patients receiving ciltacabtagene autoleucel. Grade 3 or higher CRS (2019 ASTCT grade)1 occurred in 5% (5/97) of patients, with Grade 5 CRS reported in 1 patient. The median time to onset of CRS was 7 days (range: 1-12 days). The most common manifestations of CRS included pyrexia (100%), hypotension (43%), increased aspartate aminotransferase (AST) (22%), chills (15%), increased alanine aminotransferase (14%) and sinus tachycardia (11%). Grade 3 or higher events associated with CRS included increased AST and ALT, hyperbilirubinemia, hypotension, pyrexia, hypoxia, respiratory failure, acute kidney injury, disseminated intravascular coagulation, HLH/MAS, angina pectoris, supraventricular and ventricular tachycardia, malaise, myalgias, increased C-reactive protein, ferritin, blood alkaline phosphatase and gamma-glutamyl transferase.

 

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

 

Sixty-nine of 97 (71%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of ciltacabtagene autoleucel. Forty-four (45%) patients received only tocilizumab, of whom 33 (34%) received a single dose and 11 (11%) received more than one dose; 24 patients (25%) received tocilizumab and a corticosteroid, and one patient (1%) received only corticosteroids. Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI™.

 

Monitor patients at least daily for 10 days following CARVYKTI™ infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

 

Neurologic toxicities, which may be severe, life-threatening or fatal, occurred following treatment with CARVYKTI™. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, Guillain-Barré Syndrome, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time.

Overall, one or more subtypes of neurologic toxicity described below occurred following ciltacabtagene autoleucel in 26% (25/97) of patients, of which 11% (11/97) of patients experienced Grade 3 or higher events. These subtypes of neurologic toxicities were also observed in two ongoing studies.

 

Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): ICANS occurred in 23% (22/97) of patients receiving ciltacabtagene autoleucel including Grade 3 or 4 events in 3% (3/97) and Grade 5 (fatal) events in 2% (2/97). The median time to onset of ICANS was 8 days (range 1-28 days). All 22 patients with ICANS had CRS. The most frequent (≥5%) manifestation of ICANS included encephalopathy (23%), aphasia (8%) and headache (6%).

 

Monitor patients at least daily for 10 days following CARVYKTI™ infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed.

 

Parkinsonism: Of the 25 patients in the CARTITUDE-1 study experiencing any neurotoxicity, five male patients had neurologic toxicity with several signs and symptoms of parkinsonism, distinct from immune effector cell-associated neurotoxicity syndrome (ICANS). Neurologic toxicity with parkinsonism has been reported in other ongoing trials of ciltacabtagene autoleucel. Patients had parkinsonian and non-parkinsonian symptoms that included tremor, bradykinesia, involuntary movements, stereotypy, loss of spontaneous movements, masked facies, apathy, flat affect, fatigue, rigidity, psychomotor retardation, micrographia, dysgraphia, apraxia, lethargy, confusion, somnolence, loss of consciousness, delayed reflexes, hyperreflexia, memory loss, difficulty swallowing, bowel incontinence, falls, stooped posture, shuffling gait, muscle weakness and wasting, motor dysfunction, motor and sensory loss, akinetic mutism, and frontal lobe release signs. The median onset of parkinsonism in the 5 patients in CARTITUDE-1 was 43 days (range 15-108) from infusion of ciltacabtagene autoleucel.

 

Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease, for the improvement or resolution of parkinsonism symptoms following CARVYKTI™ treatment.

 

Guillain-Barré Syndrome: A fatal outcome following Guillain-Barré Syndrome (GBS) has occurred in another ongoing study of ciltacabtagene autoleucel despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances and polyradiculoneuritis.

 

Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS.

 

Peripheral Neuropathy: Six patients in CARTITUDE-1 developed peripheral neuropathy. These neuropathies presented as sensory, motor or sensorimotor neuropathies. Median time of onset of symptoms was 62 days (range 4-136 days), median duration of peripheral neuropathies was 256 days (range 2-465 days) including those with ongoing neuropathy. Patients who experienced peripheral neuropathy also experienced cranial nerve palsies or GBS in other ongoing trials of ciltacabtagene autoleucel.

Cranial Nerve Palsies: Three patients (3.1%) experienced cranial nerve palsies in CARTITUDE-1. All three patients had 7th cranial nerve palsy; one patient had 5th cranial nerve palsy as well. Median time to onset was 26 days (range 21-101 days) following infusion of ciltacabtagene autoleucel. Occurrence of 3rd and 6th cranial nerve palsy, bilateral 7th cranial nerve palsy, worsening of cranial nerve palsy after improvement, and occurrence of peripheral neuropathy in patients with cranial nerve palsy have also been reported in ongoing trials of ciltacabtagene autoleucel. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms.

 

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): Fatal HLH occurred in one patient (1%), 99 days after ciltacabtagene autoleucel. The HLH event was preceded by prolonged CRS lasting 97 days. The manifestations of HLH/MAS include hypotension, hypoxia with diffuse alveolar damage, coagulopathy, cytopenia, and multi-organ dysfunction, including renal dysfunction. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards.

 

CARVYKTI™ REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI™ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI™ REMS.

 

Further information is available at www.CARVYKTIrems.com or 1-844-672-0067.

 

Prolonged and Recurrent Cytopenias: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI™ infusion. One patient underwent autologous stem cell therapy for hematopoietic reconstitution due to prolonged thrombocytopenia.

 

In CARTITUDE-1, 30% (29/97) of patients experienced prolonged Grade 3 or 4 neutropenia and 41% (40/97) of patients experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Day 30 following ciltacabtagene autoleucel infusion.

 

Recurrent Grade 3 or 4 neutropenia, thrombocytopenia, lymphopenia and anemia were seen in 63% (61/97), 18% (17/97), 60% (58/97), and 37% (36/97) after recovery from initial Grade 3 or 4 cytopenia following infusion. After Day 60 following ciltacabtagene autoleucel infusion, 31%, 12% and 6% of patients had a recurrence of Grade 3 or higher lymphopenia, neutropenia and thrombocytopenia, respectively, after initial recovery of their Grade 3 or 4 cytopenia. Eighty-seven percent (84/97) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Six and 11 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death.

 

Monitor blood counts prior to and after CARVYKTI™ infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines.

 

Infections: CARVYKTI™ should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening or fatal infections occurred in patients after CARVYKTI™ infusion.

Infections (all grades) occurred in 57 (59%) patients. Grade 3 or 4 infections occurred in 23% (22/97) of patients; Grade 3 or 4 infections with an unspecified pathogen occurred in 17%, viral infections in 7%, bacterial infections in 1%, and fungal infections in 1% of patients. Overall, four patients had Grade 5 infections: lung abscess (n=1), sepsis (n=2) and pneumonia (n=1).

 

Monitor patients for signs and symptoms of infection before and after CARVYKTI™ infusion and treat patients appropriately. Administer prophylactic, pre-emptive and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 10% of patients after ciltacabtagene autoleucel infusion, and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids and other supportive care, as medically indicated.

 

Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.

 

Hypogammaglobulinemia was reported as an adverse event in 12% (12/97) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 92% (89/97) of patients. Monitor immunoglobulin levels after treatment with CARVYKTI™ and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

 

Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI™ treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI™ treatment, and until immune recovery following treatment with CARVYKTI™.

 

Hypersensitivity Reactions have occurred in 5% (5/97) of patients following ciltacabtagene autoleucel infusion. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI™. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage appropriately according to the severity of the hypersensitivity reaction.

 

Secondary Malignancies: Patients may develop secondary malignancies. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc., at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy of T cell origin.

 

Effects on Ability to Drive and Use Machines: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI™ infusion.

Contacts

Investors:
Joanne Choi, Senior Manager of Investor Relations, Legend Biotech

Joanne.choi@legendbiotech.com

Crystal Chen, Manager of Investor Relations, Legend Biotech

crystal.chen@legendbiotech.com

Press:
Tina Carter, Corporate Communications Lead, Legend Biotech

tina.carter@legendbiotech.com
(908) 331-5025

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