Status: marketed in U.K., Canada and other countries

Organizations involved:

Novartis Vaccines and Diagnostics Ltd. – Manuf.; R&D; Tech.; Intl. mark.

Novartis AG – Parent

Chiron Corp. – Former

Merck Frosst Canada & Co. – Canada mark.

Sanofi Pasteur MSD – Europe mark.

Cross ref: See the entry for Meningococcal Vaccines (#497) and the entry for Meningococcal Conjugates Vaccine (#503). See the entries for Prevnar (#513) and HibTITER (#457) for further general information about polysaccharide conjugate vaccines.

Description: Menjugate is a lyophilized (freeze-dried) formulation of Neisseria meningitidis group C polysaccharide conjugated to Corynebacterium diphtheriae CRM197 protein (CRM197), a nontoxic mutant diphtheria toxin (toxoid or inactivate toxin), combined prior to use with aluminum hydroxide adjuvant. Conjugation of the N. meningitidis polysaccharide to diphtheria toxoid carrier substantially increases immune responses to the polysaccharide, particularly longer-term protection attributed to induction of T cell-dependent immune responses.

Menjugate is reconstituted prior to use with an adjuvant diluent containing aluminum hydroxide (1 mg/0.5 mL dose) and sodium chloride in sterile water. Each 0.5 mL dose of the reconstituted vaccine contains 10 µg of meningococcal C oligosaccharide conjugated to CRM197 protein (12.5 µg to 25 µg). Other excipients in the product include: mannitol, sodium phosphate dibasic heptahydrate, and sodium phosphate mono-basic monohydrate. The vaccine contains no preservative. Menjugate is stable for 24 months when stored between 2-8˚C (refrigerated).

Nomenclature: Meningococcal Vaccine, C/Novartis [BIO]; Menjugate [TR]; Neisseria meningitidis Group C vaccine [SY]

Companies.: Menjugate was developed and is manufactured by Novartis Vaccines and Diagnostics Ltd., formerly Chiron Vaccines, a subsidiary of Chiron Corp., which merged into Novartis AG in Oct. 2005. The vaccine is co-marketed in the U.K. by Novartis and Sanofi Pasteur MSD, a joint venture of Sanofi Pasteur S.A. and Merck & Co., Inc. Merck Frosst markets the vaccine in Canada.

Status: Chiron, now Novartis, will not be filing a BLA for approval of Menjugate, despite success completion of a U.S. Phase III trial. With the advent of newer multivalent conjugate vaccines, e.g., Menactra, there is little point in launching Menjugate in the U.S. (i.e., it would not be worthwhile to compete against Menjuate); and Chiron had a new quadravalent vaccine (A, C, Y, and W-135) entering U.S. Phase III trials in 2005.

Menjugate was first approved in the U.K. in March 2000. Menjugate received expedited approval in Canada in April 2001, and entered a pivotal Phase III U.S. trial in 2003. [Another group C vaccine, Men C, from Wyeth has been available in the U.K. since 1998].

Approval in the U.K., Menjugate’s first approval, was granted in March 2000 for use in children >12 months, adolescent and adults. Supplemental U.K. approval extended approval to cover those aged two months to 18 years of age. The U.K. government began a nationwide universal vaccination program with Menjugate on Nov. 1, 1999. European Union approval was granted in 2000. Approval for use in Quebec, Canada, was granted in April 2001, with the Quebec Ministry of Health selecting Menjugate for a universal vaccination campaign, which targeted some 1.7 million people between the ages of two months and 20 years.

In Feb. 2009, the U.K. Department of Health recalled 60,000 dose of Menjuate used as part of its routine Meningitis C (MenC) vaccination programme for all 3 and 4-month-old babies. The recall was due to concerns about potential contamination. Novartis had found traces of Staphylococcus aureus in the aluminium hydroxide solvent in which the vaccine is suspended, during tests on other vials - made at the same time but which had as an experiment been sent by air, rather than by surface as they usually were to Britain. It appeared that sending the vaccine in a pressurized aircraft cabin may have caused the contents of the test vials to expand, allowing contamination to enter. The solvent and vaccine lots had passed all release specification testing.

Medical: Menjugate has been shown clinically effective for prevention of group C meningococcal disease in universal vaccination programs in Quebec, Canada, and the United Kingdom (U.K.), with the vaccine reducing mortality by about 80%.

Unlike in the U.S., this group C vaccine is a required pediatric vaccine in Britain where group C strains of N. menin-gitidis cause 40% of meningitis cases. Since starting to use the vaccine in the U.K. in 1998, the rate of group C disease has decreased 75% overall and 90% in children ages 15-17.

Trials: In Nov. 2004, Chiron reported successful conclusion of its U.S. Phase III trial for Menjugate. However, it will not be filing a Biologics License Application (BLA) for the vaccine. The completed Phase III trial expands the safety and immunogenicity database for the vaccine, which is still marketed in many countries. The trial compared Menjugate to Menomune-C. Menjugate met the primary efficacy endpoint of noninferiority.

A study in the March 5, 2002 British Medical Journal indicated that meningitis C vaccine (Menjugate) is extremely cost effective and led to a marked reduction in outbreaks in the U.K. In 1999, the U.K. Department of Health added the vaccine to the routine infant immunizations it provides; and late in the year it launched a campaign offering vaccine to everyone in the country under the age of 18. Before the introduction of Menjugate, there were ~1,137 cases of meningitis C among young people every year in the U.K., resulting in at least 72 deaths. The national vaccination campaign was found to have prevented about 7,880 cases of disease and saved the lives of 845 people. The cost of the campaign (the first of its kind with a meningitis vaccine) was about £6,259/life saved, considered extremely cost effective.

Menjugate has also been shown clinically effective in universal pediatric vaccination programs in Quebec, Canada.

Market: Sales of Menjugate, primarily in the U.K., Canada, Ireland, and Hungary, totaled $43 million 2005, $66 million in 2003, $55 million in 2002, $106 million in 2001, and $115 million in 2000. In April 2005, Chiron (now Novartis) reported that sales of Menjugate were falling, because of “significant price erosion” due to less demand for monovalent meningococcal vaccines.

In mid-2008, Novartis reported having distributed more than 26 million doses of Menjugate to date.

Ongoing: Chiron, now Novartis, is developing a meningococcal types A, C, Y, and W-135 combination vaccine. Phase III trials started in 2005. As discussed in the “R&D” section of the Meningococcal Vaccines entry (#497), Chiron is also developing a type B vaccine being used in New Zealand, and is also developing a recombinant type B vaccine.

In Feb. 2004, Chiron announced it would co-develop with the Norwegian Institutes of Public Health (NIPH) a combination vaccine against Neisseria meningitidis B and C. The vaccine will combine Chiron’s Menjugate vaccine against meningococcal C disease with the NIPH’s meningococcal B vaccine.