RARITAN, N.J., October 19, 2016 – Janssen Pharmaceuticals, Inc., one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen), announced today that the U.S. Food and Drug Administration (FDA) has approved VERMOXTM CHEWABLE (mebendazole chewable 500mg tablets) for the treatment of patients one year of age and older with gastrointestinal infections caused by Ascaris lumbricoides (roundworm) and Trichuris trichiura (whipworm).
“Roundworm and whipworm are among the most prevalent forms of intestinal parasitic infections afflicting children in the world today, particularly in vulnerable and neglected communities,” said Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson. “The FDA approval of VERMOXTM CHEWABLE represents an important milestone in our efforts to develop a new therapy that safely cures patients with intestinal infections by roundworm and whipworm. We will work with the World Health Organization (WHO), other health authorities and partners to ensure VERMOXTM CHEWABLE is available as part of our longstanding global product donation program.”
Approval for VERMOXTM CHEWABLE came after the FDA granted Orphan Drug Designation and Priority Review for the new treatment, shortening the dossier review period from 10 months to six months.
The introduction of a chewable formulation of mebendazole meets a recognized global health need and is an important part of Johnson & Johnson’s R&D commitment as a signatory to the 2012 London Declaration on Neglected Tropical Diseases (NTDs). Following FDA approval and eventual WHO prequalification of the VERMOXTM CHEWABLE tablet, Johnson & Johnson plans to include the chewable version in its donation program to help reduce the burden of intestinal worms, or soil-transmitted helminths (STH), in endemic countries. Presently, there are no plans to make VERMOXTM CHEWABLE commercially available.
The efficacy of VERMOXTM CHEWABLE was evaluated in a double-blind, randomized, placebo-controlled trial conducted in three African countries (Tanzania, Ethiopia, Rwanda) in 295 pediatric patients between the ages of 1 to 16 years with roundworm and/or whipworm infections. This trial was not designed to study the effect of mebendazole on hookworm, another STH.i
Patients received a single dose of mebendazole 500mg chewable tablet or matching placebo at Day 1 (double-blind period). Clinical cure was defined as zero egg count at the end of the double-blind period (Day 19) in patients with a positive egg count at baseline. At day 19, 72 out of 86 patients (84%) with roundworm infection and 42 out of 124 patients with whipworm infection (34%) were cured on mebendazole, versus 9 out of 81 (11%) with roundworm and 9 out of 119 (8%) with whipworm on placebo. The differences in cure rate between mebendazole and placebo were statistically significant (P<0.001). The Warnings and Precautions for VERMOXTM CHEWABLE include convulsions in infants below the age of 1 year, neutropenia and agranulocytosis and serious skin reactions with the concomitant use of mebendazole and metronidazole (see Important Safety Information). Adverse reactions reported in 6,276 (adult and pediatric) patients treated with various mebendazole formulations and dosages include gastrointestinal symptoms (anorexia, abdominal pain, diarrhea, flatulence, nausea and vomiting) and rash.ii
Since 2006, Johnson & Johnson has provided mebendazole tablets as part of a major donation project through Children Without Worms (CWW), a partnership between Johnson & Johnson, GSK and The Task Force for Global Health that supports global efforts to reduce the burden of parasitic infections in children. To date, Johnson & Johnson has donated more than 1 billion doses of mebendazole and plans to donate up to 200 million doses each year through 2020 as part of its commitment to London Declaration. Together with a major annual donation of albendazole by GSK, this donation program has had a major impact on providing treatment to over 75% of the 870 million at risk children targeted by the WHO.
“Roundworm and whipworm infect millions of children, most without reliable access to safe drinking water and good sanitation,” said Dr. David Addiss, Director of CWW. “A chewable form of mebendazole fills a major gap in global treatment efforts against intestinal worms and helps us treat children when they are most vulnerable to these debilitating infections.”
VERMOXTM CHEWABLE can be administered in two different ways: It can be chewed and then swallowed by children without the need for water. Or, by adding a small amount (2 mL to 3 mL) of drinking water to the tablet in a spoon, within two minutes, the tablet turns into a soft mass with semi-solid consistency, which can then be swallowed. VERMOXTM CHEWABLE tablets must be chewed completely before swallowing and must not be swallowed whole.
The development of the new chewable tablet responds to recommendations by the WHO calling for a more child-friendly formulation of mebendazole to effectively treat young children and their families. The WHO recommends tablets should be crushed and administered to young children; older children should be encouraged to chew tablets.
About soil-transmitted helminthiasis
Soil-transmitted helminthiasis (STH) is one of the most common infections worldwide, infecting 2 billion people often living in the most underserved communities. STH is transmitted by eggs present in human feces, which can contaminate the soil in areas where sanitation is poor.
STH can affect both children and adults; however, children are more at risk. Over 270 million preschool-age children and more than 600 million school-age children live in endemic areas and are in need of treatment interventions such as safe water and sanitation. The most common species that affect people are Ascaris lumbricoides (roundworm), Trichuris (whipworm) and hookworm. STH can also lead to poor school performance in children. Recovery from STH-associated morbidity is a long term process.iii
To help lower the STH disease burden, the WHO recommends that preventative chemotherapy programs, also called mass drug administration programs, are carried out on a routine basis (in many cases twice a year) for at-risk people, particularly children, living in endemic areas.iv
STH particularly impairs physical and cognitive development of affected children. It can also lead to health complications such as intestinal bleeding, loss of appetite, diarrhea and reduced absorption of micro- and macro-nutrients. In severe cases, STH can cause complications such as intestinal obstruction. It is important to keep worm burdens as low as possible to prevent morbidity and protect children during the critical phase of their development.v
About VERMOXTM Chewable (mebendazole chewable 500mg tablets)
VERMOXTM Chewable (mebendazole chewable 500mg tablets) is indicated for the treatment of patients one year of age and older with gastrointestinal infections caused by Ascaris lumbricoides (roundworm) and Trichuris trichiura (whipworm).
There are several registered formulations of mebendazole marketed by Janssen worldwide. Janssen’s 500mg VERMOXTM solid oral tablet is currently used in the mass treatment of single or mixed intestinal infections by whipworm, roundworm and Ancylostoma duodenale and Necator americanus (hookworm).
Mebendazole interferes with cellular tubulin formation in intestinal worms which leads to the death of the worm.
IMPORTANT SAFETY INFORMATION (PROFESSIONAL)
CONTRAINDICATIONS: Persons with a known hypersensitivity to the drug or its excipients.
WARNINGS AND PRECAUTIONS
Risk of Convulsions: Convulsions have been reported in infants below the age of 1 year during post-marketing experience with mebendazole.
Hematologic Effects: Agranulocytosis and neutropenia have been reported with use at higher doses and for more prolonged durations than is recommended for the treatment of soil-transmitted helminth infections. Monitor blood counts if used at higher doses or for prolonged duration.
Metronidazole Drug Interaction and Serious Skin Reactions: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) have been reported with the concomitant use of mebendazole and metronidazole. Avoid concomitant use of VERMOXTM CHEWABLE and metronidazole.
Drug Interactions: Concomitant use of VERMOXTM CHEWABLE and metronidazole should be avoided.
USE IN SPECIFIC POPULATIONS
Pregnancy: The available published literature on mebendazole use in pregnant women has not reported a clear association between mebendazole and a potential risk of major birth defects or miscarriages. Several published studies, including prospective pregnancy registries, case-control, retrospective cohort, and randomized controlled studies, have reported no association between mebendazole use and a potential risk of major birth defects or miscarriage. Overall, these studies did not identify a specific pattern or frequency of major birth defects with mebendazole use. However, these studies cannot definitely establish the absence of any mebendazole-associated risk because of methodological limitations, including recall bias, confounding factors and, in some cases, small sample size or exclusion of first trimester mebendazole exposures.
Lactation: Limited data from case reports demonstrate that a small amount of mebendazole is present in human milk following oral administration. There are no reports of effects on the breastfed infant, and the limited reports on the effects on milk production are inconsistent. The limited clinical data during lactation precludes a clear determination of the risk of VERMOX™ CHEWABLE to a breastfed infant; therefore, developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VERMOX™ CHEWABLE and any potential adverse effects on the breastfed infant from VERMOX™ CHEWABLE or from the underlying maternal condition.
Pediatric Use: The safety and effectiveness of VERMOX™ CHEWABLE have not been established in pediatric patients less than one year of age. Convulsions have been reported with mebendazole use in this age group.
Overdosage: In patients treated at dosages substantially higher than recommended or for prolonged periods of time, the following adverse reactions have been reported: alopecia, reversible transaminase elevations, hepatitis, agranulocytosis, neutropenia, and glomerulonephritis. In the event of accidental overdose, gastrointestinal signs/symptoms may occur. There is no specific antidote.
Adverse reactions reported in clinical trials were anorexia, abdominal pain, diarrhea, flatulence, nausea, vomiting and rash.
Please see full Prescribing Information
About Johnson & Johnson’s VERMOXTM (mebendazole) donation commitment
In 2006, Johnson & Johnson founded Children Without Worms in collaboration with the Task Force for Global Health and started the donation of VERMOXTM. The partnership is dedicated to the treatment and prevention of STH in children. WHO is the partner that coordinates the global supply of medicines and supports country governments in the distribution of the medicines via school programs in endemic countries.
In 2012, Johnson & Johnson endorsed the London Declaration on Neglected Tropical Diseases and committed to expanding the donation to 200 million doses of VERMOXTM each year through 2020, as well as to exploring the development of a new chewable formulation to provide treatment for younger children. With FDA approval and subsequent WHO Prequalification, the chewable tablet will replace the current solid tablet in donation programs.
For more information about Children Without Worms visit: http://www.childrenwithoutworms.org/.
About the Janssen Pharmaceutical Companies
At the Janssen Pharmaceutical Companies of Johnson & Johnson, we are working to create a world without disease. Transforming lives by finding new and better ways to prevent, intercept, treat and cure disease inspires us. We bring together the best minds and pursue the most promising science. We are Janssen. We collaborate with the world for the health of everyone in it. Learn more at www.janssen.com. Follow us at @JanssenGlobal.
About Johnson & Johnson Global Public Health
We have a robust portfolio of innovative products, expertise and experience focused on maternal, newborn and child health, HIV/AIDS and tuberculosis (TB). We use holistic approaches to deliver better health outcomes in addition to quality outputs. And we bring to bear our deep expertise, talent, operational excellence, community engagement and partnerships to build a healthy world free of disease. We work in partnership with governments, donors, non-profits and multilateral institutions to develop and deliver integrated, evidence-based solutions for public health. Learn more at www.jnj.com/global-public-health and follow us @JNJGlobalHealth.
+47 488 425 00
+1 (908) 405-1144
+1 (732) 524-3922
Cautions Concerning Forward-Looking Statements
This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and donation commitments. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Pharmaceuticals, Inc., Johnson & Johnson and/or their affiliates. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product development, including the uncertainty of clinical success and of obtaining regulatory approvals; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; manufacturing difficulties and delays; and trends toward health care cost containment. A further list and description of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended January 3, 2016, including in Exhibit 99 thereto, and the company's subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. The Janssen Pharmaceutical Companies, Johnson & Johnson and their affiliates do not undertake to update any forward-looking statement as a result of new information or future events or developments.
i Janssen data on file.
iii World Health Organization. Media centre. Soil-transmitted helminth infections. Available at http://www.who.int/mediacentre/factsheets/fs366/en/. Last accessed June 2016.
iv World Health Organization. Preventive chemotherapy in human helminthiasis. Coordinated use of anthelminthic drugs in control interventions: a manual for health professionals and programme managers. Available at http://apps.who.int/iris/bitstream/10665/43545/1/9241547103_eng.pdf. Last accessed October 2016.
v World Health Organization, Intestinal worms. Available at http://www.who.int/intestinal_worms/more/en/. Last accessed October 2016.