Sanofi-Aventis Menactra Approved; Launch Awaits ACIP Recommendations

Sanofi-Aventis' launch of its meningococcal conjugate vaccine Menactra will await formal recommendations for use by the Centers for Disease Control & Prevention's Advisory Committee on Immunization Practices next month.

FDA approved Menactra Jan. 14 for "active immunization of adolescents and adults 11-55 years of age for the prevention of invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, Y and W-135," labeling states.

ACIP recommendations will play a major role in determining the initial pace of demand for the product, Sanofi-Aventis said.

ACIP "has formed a working group that is updating the recommendations for the prevention and control of meningococcal disease, including routine meningococcal vaccination of one or more birth cohorts (e.g., 11-12 year olds) and of selected college students," Sanofi-Aventis said in its Jan. 17 announcement of Menactra's approval.

"ACIP is expected to approve any changes in recommendations during the February 2005 committee meeting," Sanofi-Aventis said. The committee scheduled to meet Feb. 10-11 in Atlanta.

ACIP's proposed recommendations for meningococcal conjugate vaccine - 4-valent call for vaccinating children ages 11-12; 12-19 year olds as part of a catch-up campaign; college freshmen living in dorms and other groups at increased risk (¹ (Also see "Sanofi-Aventis Menactra Market Is $3.5 Bil. Over 10 Years, CDC Says" - Pink Sheet, 8 Nov, 2004.), p. 24).

Sanofi-Aventis plans to expand its indication to include adults over 55 and children under 11.

The company will submit an sBLA supporting use of Menactra in 2-10 year olds by February.

"Studies demonstrating safety and effectiveness of Menactra vaccine in individuals 2 to 10 years of age are deferred until February 2005 when the BLA Supplement will be submitted," the Menactra ² approval letter states.

"In addition, a deferral of pediatric studies with Menactra vaccine in individuals less than 2 years of age is justified as clinical development in this age range is ongoing."

Studies in children younger than 2 years of age have been initiated; additional data in this population will be submitted to the Center for Biologics Evaluation & Research by December 2006, the letter notes.

Sanofi-Aventis will also evaluate Menactra's safety and efficacy in subjects over 55 years of age in a study to be initiated by January 2006.

In September, FDA's Vaccines & Related Biological Products Advisory Committee recommended that Sanofi-Aventis conduct long-term efficacy and safety studies for Menactra post-approval (³ (Also see "Menactra Needs Long-Term Safety, Efficacy Studies Post-Approval – Cmte." - Pink Sheet, 27 Sep, 2004.), p. 36).

Menactra will be priced in the $70 range, comparable to Sanofi-Aventis' polysaccharide meningococcal vaccine Menomune , the company said.

Sanofi-Aventis has cited Menactra's potential for longer antibody persistence, the ability to prime and boost, absence of hyporesponsiveness and strengthening of herd immunity as possible advantages over Menomune (⁴ (Also see "Aventis Pegs Injectable Flu Vaccine As Key Sales Growth Driver" - Pink Sheet, 6 Oct, 2003.), p. 40).

However, the current label for Menactra does not allow for comparative claims.

"You should not make a comparative promotional claim or claim of superiority over other products unless you have submitted data to support such claims to us and had them approved," the approval letter states.

Sanofi-Aventis said it will continue to manufacture Menomune until Menactra is approved for all age groups.

Sanofi-Aventis has finished the construction phase for a new facility to manufacture Menactra and Menomune in Swiftwater, Pa. The company's timeline calls for the plant to come on-line in late 2006 or early 2007.

Menactra is currently manufactured at the existing Menomune facility.

Until the new facility is available, Menactra production capacity will be limited. Sanofi-Aventis "will work closely with the CDC in an effort to ensure production schedules that will support an orderly implementation of the anticipated new immunization recommendations," the company said.

Approval of Menactra was based on demonstration of non-inferiority to Menomune.

Menactra immunogenicity was demonstrated in two randomized, comparative, active-controlled trials, one in adolescents 11-18 years old and one in adults 18-55 years old, ⁵ labeling states.

In both trials, "immune responses to Menactra vaccine and Menomune-A/C/Y/W-135 were similar for all four serogroups."

Sanofi-Aventis also studied concomitant administration of Menactra with the Td vaccine (Tetanus and Diphtheria Toxoids Adsorbed For Adult Use) and with the Typhim Vi vaccine.

"The proportion of participants with a 4-fold or greater rise in [Serum Bactericidal Assay with baby rabbit complement] titer was higher when Menactra vaccine was given concomitantly with Td than when Menactra vaccine was given one month following Td. The clinical relevance of this finding has not been fully evaluated," labeling states.

In the Menactra plus Typhim Vi study, immune responses for each vaccine when given concomitantly were similar to the responses when the vaccines were given 28 days apart.

Sanofi-Aventis evaluated Menactra's safety in two studies comparing the conjugated vaccine to Menomune.

"Serious adverse events reported within a 6-month time period following vaccination occurred at the same rate (1.3%) in the Menactra vaccine and Menomune-A/C/Y/W-135 vaccine groups. The events reported were consistent with events expected in healthy adolescent and adult populations," labeling states.

Menactra is administered intramuscularly in a single dose of 0.5 mL.