Regulatory Decision Summary for ACAM2000

The purpose of this extraordinary use new drug submission is to seek marketing authorization, pursuant to section C.08.004 of the Food and Drugs Regulations, for ACAM2000 (vaccinia virus, live) as a smallpox vaccine for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection, filed by Emergent Product Development Gaithersburg Inc.

After evaluation of the submitted data package, Health Canada authorized ACAM2000 smallpox vaccine as a new vaccine for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection. The sale of the drug product for that indication is restricted to federal, provincial and territorial, and municipal government(s).

Authorization was based non-clinical (animal) data and on two studies that demonstrate that ACAM2000 is non-inferior to Dryvax (an older smallpox vaccine). One study was conducted in subjects who had never been vaccinated for smallpox (naive). The other study was conducted in subjects who had previous smallpox vaccination. Specifically, the clinical studies were multi-center, randomized, controlled comparing ACAM2000 to Dryvax. The primary endpoint in both studies were the proportion of subjects with a successful vaccination/revaccination as measured by a major cutaneous reaction or “take” and antibody titer response.

To compare the efficacy in persons who had never been previously vaccinated against smallpox , 780 subjects received ACAM2000 and 257 subjects received Dryvax. The recipients included males and females between the ages of 18 and 30 years. The percentage of scar formation at the vaccination skin site or "take rates" in subjects who received ACAM2000 was similar to that of subjects who received Dryvax. The immune response generated was acceptable for ACAM2000.

In the study of persons previously vaccinated against smallpox, 1,242 subjects received ACAM2000 and 405 subjects, including males and females from 31-84 years old, received Dryvax. The percentage of subjects who developed an immune response was similar to that of Dryvax. ACAM2000 also was found to be acceptable for use for revaccination in those previously vaccinated for smallpox.

The vaccine may cause serious heart problems called myocarditis and/or pericarditis (swelling of the heart tissues), or heart attack or other diseases of the heart. In the ACAM2000 clinical trial experience, seven individuals of the 2,983 ACAM2000 recipients and three individuals of the 868 Dryvax first-time recipients were suspected to have myocarditis/pericarditis. There were no cases in those subjects who had been vaccinated previously.

Serious health problems, including those that are life-threatening, can also occur in unvaccinated people who are accidentally infected by someone who has recently received the vaccine.

Commonly observed side effects include: itchiness, redness, fever, or pain at the vaccination site, feeling tired or unwell, body ache, mild rash.

The vaccine is not recommended for use by the general population, as there is no smallpox disease in the world. It will not be available to the general public, but reserved by the Federal government in case it is ever needed.

The vaccine is approved for active immunization against smallpox disease for persons determined to be at high risk for smallpox infection as it is considered that the benefits of the vaccine would outweigh the risks of adverse effects in the case of a threat of smallpox or an outbreak. Detailed information regarding the use of the vaccine, including the contraindications and potential risks is detailed in the product monograph.

A Risk Management Plan (RMP) for ACAM2000 was reviewed by Health Canada and considered acceptable.

The chemistry and manufacturing information submitted for ACAM2000 has demonstrated that the drug substance and drug product can be consistently manufactured to meet the approved specifications.

Following review and requested revisions, the final labelling and Product Monograph were considered to be acceptable.

Overall, the benefit-harm-uncertainty profile was favourable for ACAM2000 for the approved indication. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about ACAM2000, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.