U.S. Food and Drug Administration Approves Lampit® (nifurtimox) for the Treatment of Chagas Disease in Children

• Only Chagas disease treatment approved in U.S. for use in children from birth to less than 18 years of age¹

• New, dividable tablet specially formulated to disperse in water to assist in administration for pediatric patients^1-3

Bayer announced today that the United States Food and Drug Administration (FDA) has approved Lampit^® (nifurtimox) for use in pediatric patients (from birth to less than 18 years of age and weighing at least 2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis) caused by Trypanosoma cruzi (T. cruzi).¹ Lampit, an antiprotozoal medication will be available in a new, dividable tablet that can be split on the scored lines by hand.^1-3 According to prescribing instructions, the tablet is specially formulated to disperse in water, which can aid in the dosing and administration to pediatric patients who may have difficulty swallowing whole or half tablets.^1-3

This indication is approved under accelerated approval based on the number of treated patients who became immunoglobulin G (IgG) antibody negative or who showed an at least 20% decrease in optical density on two different IgG antibody tests against antigens of T. cruzi. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Chagas is an infectious tropical disease that affects an estimated 300,000 people in the U.S.⁴ The disease is endemic throughout much of Latin America, though it is a growing health concern in the U.S.^5,6 Approval of a treatment for pediatric patients is an important milestone.

"Chagas disease can strike at any age, and early detection and treatment are important. This is especially relevant for children," said Aleksandra Vlajnic, MD, senior vice president and head of Medical Affairs for the Americas at Bayer. "The importance of treating children is a major reason behind Bayer's collaboration with health authorities to enhance access to Lampit as a means to provide treatment for Chagas disease."

The FDA approval is based on results from the Chagas disease in children treated with nifurtimox study, the first part of the largest Phase III program ever conducted in pediatric patients for the treatment of Chagas disease.

"In the study, Lampit showed good antiprotozoal activity in patients from 0 to 17 years old," said Jaime Altcheh, MD, head of the Department of Parasitology and Chagas disease at the Ricardo Gutierrez Children's Hospital in Buenos Aires, Argentina, and coordinating investigator of the Phase III trial.

The Phase III Lampit study was the first part of a prospective, randomized (to dosing regimen), double-blind evaluation of the efficacy, safety, and pharmacokinetics of nifurtimox in 330 children with Chagas disease.¹ The study was conducted at 25 investigational sites in Argentina, Bolivia, and Colombia between 2016 and 2018.⁷ In the study, 330 pediatric patients with serologic evidence of T. cruzi infection (without Chagas disease-related cardiovascular and/or gastrointestinal symptoms) were randomly assigned in a 2:1 fashion to receive either a 60-day (n=219) or a 30-day (n=111) Lampit treatment regimen, and were followed up for one year after end of treatment.¹ The results showed superiority in favor of the nifurtimox 60-day arm compared to the nifurtimox 30-day arm (not an approved dosing regimen). For additional clinical trial information, go to clinicaltrials.gov NCT02625974 and see full prescribing information.^1,7

The study will continue with a second part (Lampit SECURE) to follow patients for an additional three years to confirm efficacy and safety.

Now that Lampit is approved for pediatric use in the U.S., Bayer is working to ensure access to the drug for all patients through retail channels. Commercially insured patients may qualify for a $0 co-pay to help with their out-of-pocket costs. For uninsured patients who cannot afford Lampit, the Bayer U.S. Patient Assistance Foundation, a charitable organization, will help eligible patients obtain the prescription medication at no cost. Restrictions apply. See Program Details for full information. Lampit is not approved in the U.S. for use in adults 18 years of age or older.

About Chagas Disease

Chagas disease is caused by the Trypanosoma cruzi parasite and is primarily transmitted to humans via the feces of infected triatomines, insects that are also known as "kissing bugs" where the disease is present. Chagas disease can also be transmitted by infected organ transplantation, infected blood transfusion, during pregnancy or birth from an infected mother to her child, and less frequently through ingestion of contaminated food.^4-6,8-10

Although the disease can be curable when detected and treated soon after the infection, untreated individuals become carriers and move to the chronic phase of the disease. Approximately 30% of these people may experience life-threatening cardiovascular and gastrointestinal complications.¹¹

According to the World Health Organization (WHO), 6 to 7 million people around the world are infected with Chagas disease.^12,13 The majority of infected individuals are in Latin America, where Chagas remains one of the region's biggest public health problems, causing incapacity in infected individuals and more than 10,000 deaths per year.¹⁴ Today, less than 1% of people infected with Chagas disease worldwide are treated due to low disease awareness and limited access to treatment.¹³

Bayer's Historical Commitment to Chagas Disease Patients

After discovering nifurtimox at its laboratories in Wuppertal, Germany, Bayer first introduced nifurtimox as Lampit in Argentina in the 1970s, and shortly afterwards made the medication available in other Latin American countries. Nifurtimox is on the list of WHO's Lists of Essential Medicines, a list of safe and effective medicines needed for priority conditions in a health system.¹⁵ In 2002, the WHO entered into an agreement with Bayer by which the company would provide the medication as a donation, as well as financial resources for logistics and distribution, disease education and training, and disease surveillance activities.¹⁶ Today, Lampit is one of only two drugs available in the world to treat Chagas disease.^17,18

Lampit is currently registered in several Latin American countries (Argentina, Uruguay, Chile, El Salvador, Guatemala, and Honduras) for the treatment of acute and chronic Chagas disease in adults and children. The company is working to improve access to Lampit by expanding the number of countries with registrations for the product.

Indication

Lampit^® (nifurtimox) is an antiprotozoal medication indicated for use in pediatric patients (from birth to less than 18 years of age and weighing at least 2.5 kg) for the treatment of Chagas disease (American Trypanosomiasis) caused by Trypanosoma cruzi (T. cruzi).¹ This indication is approved under accelerated approval based on the number of treated patients who became immunoglobulin G (IgG) antibody negative or who showed an at least 20% decrease in optical density on two different IgG antibody tests against antigens of T. cruzi. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).¹

IMPORTANT SAFETY INFORMATION

Contraindications

LAMPIT tablets are contraindicated in:

• Patients with known hypersensitivity to nifurtimox or any of the excipients in LAMPIT
• Patients who consume alcohol during treatment

Warnings and Precautions

Potential for Genotoxicity and Carcinogenicity

Genotoxicity

Genotoxicity of LAMPIT has been demonstrated in humans, in vitro in several bacterial species and mammalian cell systems, and in vivo in rodents.

A study evaluating the cytogenetic effect of nifurtimox in pediatric patients ranging from 7 months to 14 years of age with Chagas disease demonstrated a 13-fold increase in chromosomal aberrations.

Carcinogenicity

Carcinogenicity has been observed in mice and rats treated chronically with nitrofuran agents which are structurally similar to nifurtimox. Similar data have not been reported for LAMPIT. It is not known whether LAMPIT is associated with carcinogenicity in humans.

Embryo-Fetal Toxicity

Based on findings from animal studies, LAMPIT can cause fetal harm when administered to a pregnant woman. In animal reproduction studies, nifurtimox administered orally to pregnant mice, rats, and rabbits during organogenesis was associated with reduced fetal body weights in rodents, and abortions, fetal death, and smaller litter sizes in rabbits at doses approximately equivalent to and 2-times, respectively, the maximum recommended human dose (MRHD) of 10 mg/kg/day. Fetal malformations were observed in pregnant rabbits administered nifurtimox doses less than the MRHD.

Advise pregnant women of the potential risk to a fetus. Pregnancy testing is recommended for females of reproductive potential prior to initiating treatment with LAMPIT. Advise females of reproductive potential to use effective contraception during treatment with LAMPIT and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use condoms during treatment and for 3 months after the last dose of LAMPIT.

Worsening of Neurological and Psychiatric Conditions

Patients with a history of brain injury, seizures, psychiatric disease, or serious behavioral alterations may experience worsening of their conditions when receiving LAMPIT. Administer LAMPIT under close medical supervision in these patients and in patients who develop neurological disturbances or psychiatric drug reactions.

Hypersensitivity

Cases of hypersensitivity have been reported in patients receiving therapy with nifurtimox. The hypersensitivity could be a reaction induced by nifurtimox or an immune response triggered by Chagas disease during treatment. Hypersensitivity reactions could be accompanied by hypotension, angioedema (including laryngeal or facial edema), dyspnea, pruritus, rash or other severe skin reactions. At the first sign of serious hypersensitivity, discontinue treatment with LAMPIT.

Decreased Appetite and Weight Loss

Decreased appetite and weight loss were reported in patients treated with LAMPIT in the clinical trials. During treatment with LAMPIT, patients can lose their appetite or experience nausea/vomiting which can result in weight loss. Check body weight every 14 days, as the dosage may have to be adjusted.

Porphyria

Treatment with nitrofuran derivatives, such as LAMPIT, may precipitate acute attacks of porphyria. Administer LAMPIT tablets under close medical supervision in patients with porphyria.

Adverse Reactions

The most frequently reported adverse reactions (≥1%) in patients treated with nifurtimox were vomiting (14.6%); abdominal pain (13.2%); headache (12.8%); decreased appetite (10.5%); nausea (8.2%); pyrexia (7.3%); rash (5.5%), diarrhea (4.6%), weight decreased (2.7%); anemia (2.7%), dizziness (2.7%), eosinophilia (2.3%) and urticaria (2.3%).

For additional important risk and use information, please see the full Prescribing Information and Instructions for Use. You are encouraged to report side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

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 benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability, and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to www.bayer.us.

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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. Lampit (nifurtimox) tablets, for oral use prescribing information. Bayer HealthCare Pharmaceuticals Inc., 2020.
2. Patient information: Lampit (nifurtimox) tablets, for oral use. Bayer HealthCare Pharmaceuticals Inc., 2020.
3. Instructions for use: Lampit (nifurtimox) tablets, for oral use. Bayer HealthCare Pharmaceuticals Inc., 2020.
4. Bern C, Montgomery SP. An estimate of the burden of Chagas disease in the United States. Clin Infect Dis. 2009;49: e52‐54.
5. Chagas disease: provider fact sheet. Centers for Disease Control and Prevention website, 2018. https://www.cdc.gov/parasites/chagas/resources/factsheet.pdf. Accessed April 21, 2020.
6. Montgomery SP, Parise ME, Dotson EM, Bialek SR. What do we know about Chagas disease in the United States? Am J Trop Med Hyg.2016;95(6):1225-1227.
7. Prospective study of a pediatric nifurtimox formulation for Chagas' disease (CHICO). U.S. Department of Health and Human Services, National Institutes of Health, National Library of Medicine; 2020. https://clinicaltrials.gov/ct2/show/results/NCT02625974?term=CHICO&cond=Chagas+Disease&draw=2&rank=1&view=results. Accessed July 27, 2020.
8. Chagas disease: an emerging public health concern. U.S. Food and Drug Administration Office of Minority Health website. https://www.fda.gov/media/94691/download. Accessed April 21, 2020.
9. Bonney KM. Chagas disease in the 21^st century: a public health success or an emerging threat? Parasite. 2014;21:11.
10. Pereira KS, Schmidt FL, Barbosa RL, et al. Transmission of chagas disease (American trypanosomiasis) by food. Adv Food Nutr Res. 2010;59:63-85.
11. Edwards MS. Addressing the challenges of Chagas disease: an emerging health concern in the United States. Infect Dis Clin Pract. 2017;25(3):118-125.
12. Meymandi S, Hernandez S, Park S, Sanchez DR, Forsyth C. Treatment of Chagas disease in the United States. Curr Treat Options Infect Dis. 2018;10:373-388.
13. Chagas disease (American trypanosomiasis). World Health Organization website, 2020. https://www.who.int/health-topics/chagas-disease#tab=tab_1. Accessed June 5, 2020.
14. Chagas disease (American trypanosomiasis). Epidemiology. World Health Organization website, 2020. https://www.who.int/chagas/epidemiology/en/. Accessed June 5, 2020.
15. World Health Organization. World Health Organization model lists of essential medicines, 21st edition, 2019. https://www.who.int/medicines/publications/essentialmedicines/en/. Accessed July 9, 2020.
16. Tropical diseases: Chagas disease. Bayer AG website. https://pharma.bayer.com/chagas-disease. Accessed July 17, 2020.
17. Making treatment safer and more effective for people living with Chagas disease: an update on DNDi's Chagas disease portfolio. Drugs for Neglected Diseases Initiative, 2018. https://www.dndi.org/wp-content/uploads/2018/12/DNDi_Chagas_2018.pdf. Accessed April 22, 2020.
18. Stimpert KK, Montgomery SP. Physician awareness of Chagas disease, USA. Emerg Infect Dis. 2010;16:871-872.

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©2020 Bayer. All rights reserved. August 2020.

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