Typographical errors corrected.
Associate Professor Richard Robson opened the teleconference at 8.15pm and welcomed members to the meeting.
Present: Associate Professor R Robson (Chair), Dr D Gray, Dr M Harrison-Woolrych, Professor R Laverty, Dr D Pethica, Mr G Spears, Dr R Ellis-Pegler and Mr R Allman (Team Leader, Evaluation Team, Medsafe, Ministry of Health who acted as Secretary).
Apologies: Dr R Acland, who provided comment via the Chairman prior to the teleconference. Dr DeBoyer, Dr Robinson and Dr A Macleod could not be contacted prior to the teleconference.
Guests: Dr Stewart Reid for the final part of the teleconference at the Chairman's invitation.
Conflict of interest: When Dr Reid joined the teleconference, he stated that he had a conflict of interest as he has been a member of the Meningococcal B Vaccine Project Committee for the past five years. Dr Reid was not involved in the decision concerning the licensure of the vaccine.
The conflict of interest was noted but did not influence the discussions or decision.
NEW MEDICINE APPLICATION UNDER SECTION 23.
MeNZB (Meningococcal B) injection suspension 25mcg/0.5mL. TT50-7090.
The Committee considered an application from Chiron for MeNZB (meningococcal B) vaccine.
The Chairman advised the Committee that the object was to decide if there was sufficient evidence to confirm the Vaccine Sub-Committee recommendation for approval under Section 23 of the Medicines Act 1981.
The Chairman noted that the quality and manufacturing data (Module 3, with Module 2 summaries) relating to the Meningococcal B vaccine (MeNZB) produced by Chiron S.r.L. have been assessed by the Medicines and Healthcare Products Regulatory Authority (MHRA) and discussed with the National Institute of Biological Standards and Control UK (NIBSC).
Clinical data have been discussed by the VSC on 5 April 2004 and a recommendation made that the data supported provisional consent subject to satisfactory manufacturing and quality data.
Background: New Zealand is in the thirteenth year of an epidemic of Group B Meningococcal disease. There is currently no commercially available group B meningococcal vaccine against the New Zealand epidemic strain. International experience of similar outbreaks suggests that the epidemic may continue in this country for a further 6 to 10 years. There have been 500-600 cases per year. The current rate in the northern parts of New Zealand is more than 20/100,000. More than 80% of the disease occurs in people under 20 years of age. The highest rate of disease is in Maori and Pacific Island infants under the age of one year. Although the death rate in New Zealand is commendably low at 3.2%, some 15-20% of the survivors are left with a long-term disability, including sensory-neural deafness, skin, digit or limb loss and neurological damage.
An Immunisation Programme with a 'tailor-made' vaccine, containing OMV antigen for the most frequent New Zealand group B sub-type is seen as the most expeditious approach to bring this epidemic to a halt.
The Committee considered the Clinical and Part II issues that have been raised and discussed these issues in detail. It was noted that the safety-monitoring programme is seen as a very important component of the consideration of the vaccine by the Committee.
The Committee noted that there are a number of issues relating to the manufacturing and quality data that are to be addressed by Chiron. The Committee noted the commitment from Chiron to produce those data.
The Committee discussed the current levels of disease in the Auckland region and noted that the benefits of the vaccine appear to be clear when viewed in this context.
The Committee agreed that there is currently insufficient clinical data for full approval under section 21 of the Medicines Act 1981.
The Committee noted that the vaccine cannot yet be approved for individuals under 6 months of age, as the clinical trials in this age group are not yet complete.
The Committee raised the question of informed consent and the Chairman confirmed that this is not a regulatory issue.
The Committee noted that not all members had seen the clinical data due to the short notice of the teleconference. The Chairman invited Dr Reid to join teleconference to provide an overview of the trials and the safety-monitoring programme.
Dr Reid reported as follows:
Clinical trials of MeNZB have been conducted in Adults, 8-12 year old school children, 16-24 month old toddlers and 6-8 month infants. 25 adults were involved in each limb of the adult study, one of which received the candidate vaccine in the dosage proposed for licensure. In the other studies at least 200 in each age group received the candidate vaccine.
In the school children and toddlers the control vaccine was the Norwegian OMV vaccine MenBvac while in infants the control vaccine was Menjugate, the protein conjugate capsular polysaccharide vaccine against group C meningococci which is produced by Chiron and is licensed in Europe and other jurisdictions.
The percentage of individuals sustaining a fourfold rise in serum bactericidal titre was 91%, 75%, 74% and 75% respectively in the adult, school child, toddler and infant studies respectively.
As expected, injection site reactions occurred in a high percentage of individuals but most subsided within a few days. Systemic reactions were at a much lower rate and no serious adverse events attributable to the vaccine have been reported.
The Committee noted that the vaccine is locally reactogenic and that, in general, the reaction is worse on day 2, but settles down by days 3 or 4. A severe reaction is defined as crying when the limb is moved. The Committee noted that children who have severe reaction to the first dose are approximately twice as likely to have a severe reaction to subsequent doses than those who had a mild reaction to the first dose. However the majority of children who suffered severe reactions have reactions of lesser severity with subsequent doses.
The Committee noted no febrile convulsions were seen in the clinical trials and that pyrexia occurs in a relatively small number (5-6%) of those injected, although pyrexia is not seen as a problem with the vaccine.
The Committee noted that information concerning the overall efficacy of the vaccine will be obtained during the controlled roll out process.
The committee recommended section 23 approval for the Meningococcal B Vaccine and agreed that the benefits out weighed the risks.
The committee was satisfied that the outstanding Part II data queries will be answered and that the monitoring that has been proposed for the clinical introduction of the vaccine will be able to identify safety and efficacy concerns.
There being no further business, the Chair thanked members for their attendance and closed the teleconference at 9.35pm.