Merck & Co., Inc. Obtains Exclusive U.S. Marketing Rights for AFLURIA®, Seasonal Influenza Vaccine from CSL Biotherapies

Merck & Co., Inc. announced today that the Company has entered into an exclusive agreement with CSL Biotherapies, a subsidiary of CSL Limited, to market and distribute AFLURIA^® (Influenza Virus Vaccine), CSL's seasonal influenza (flu) vaccine, in the U.S., for the 2010/2011-2015/2016 flu seasons. CSL and Merck have been partners in vaccine development and marketing since 1980.

Under the terms of the agreement, Merck will assume responsibility for all aspects of commercialization of AFLURIA in the U.S. CSL will supply AFLURIA to Merck and will retain responsibility for marketing the vaccine outside the U.S. Specific financial details of the agreement were not disclosed.

AFLURIA was approved by the U.S. Food and Drug Administration (FDA) in September 2007. It is indicated for the active immunization of persons age 18 years and older against influenza disease caused by influenza virus subtypes A and type B present in the vaccine. This indication is based on immune response elicited by AFLURIA, and there have been no controlled trials demonstrating a decrease in influenza disease after vaccination with AFLURIA.

"Adult vaccines are an integral part of preventive healthcare and continue to be a strong focus for Merck," said Margaret G. McGlynn, president, Merck Vaccines and Infectious Diseases. "AFLURIA is an important addition to our robust adult vaccine portfolio and provides an opportunity for us to help address the public health need for flu vaccination in the U.S."

With the addition of seasonal flu vaccine, Merck will market eight of the 10 vaccines on the recommended immunization schedule for adults in the U.S.

CSL Biotherapies recently announced that the FDA licensed a new vaccine filling and packaging facility in Kankakee, Illinois. The facility includes a high-speed, single-dose vaccine syringe filling line and will primarily provide filling and packaging services for influenza vaccine supply to the U.S. market.

About Influenza

The flu is a contagious respiratory illness caused by influenza viruses. According to the U.S. Centers for Disease Control and Prevention, on average, 5 percent to 20 percent of the population gets the flu every year in the U.S. Everyone is at risk for the flu, but some people, such as older people and people with certain health conditions, are at high risk for serious flu complications. In the U.S., annual epidemics of influenza occur typically during the late fall through early spring seasons.

Important safety information about AFLURIA

AFLURIA should not be administered to individuals with hypersensitivity to eggs or chicken protein or other components of AFLURIA, or to anyone who has had a life-threatening reaction to previous influenza vaccination.

The most common injection-site adverse reactions were tenderness, pain, redness and swelling. The most common systemic adverse reactions were headache, malaise and muscle aches.

Immunocompromised persons may have a diminished immune response to AFLURIA. If Guillain-Barre syndrome has occurred within six weeks of receipt of prior influenza vaccine, the decision to give AFLURIA should be based on careful consideration of the potential benefits and risks.

In four clinical studies, 343 subjects 65 years of age and older received AFLURIA. Hemagglutination-inhibiting (HI) antibody responses in geriatric subjects were lower after administration of AFLURIA in comparison to younger adult subjects. Adverse event rates were generally similar in frequency to those reported in subjects 18 years of age to less than 65 years of age, although some differences were observed.

Vaccination with AFLURIA may not protect all individuals.

About Merck

Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-looking statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2008, and in any risk factors or cautionary statements contained in the Company's periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.

Prescribing information for AFLURIA^® is attached.

CSLTM   Package insert for the 2009-2010 Influenza Season

Influenza Virus Vaccine STN BL 125254/118

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use AFLURIA^® safely and effectively. See full prescribing information for AFLURIA^®.

AFLURIA^®, Influenza Virus Vaccine

Suspension for Intramuscular Injection

2009-2010 Formula

Initial U.S. Approval: 2007

----------------------------INDICATIONS AND USAGE-----------------------------

• AFLURIA^® is an inactivated influenza virus vaccine indicated for active immunization of persons ages 18 years and older against influenza disease caused by influenza virus subtypes A and type B present in the vaccine. (1)
• This indication is based on the immune response elicited by AFLURIA^®; there have been no controlled clinical studies demonstrating a decrease in influenza disease after vaccination with AFLURIA^®. (14)

-------------------------DOSAGE AND ADMINISTRATION----------------------

• A single 0.5 mL dose for intramuscular injection. (2)

------------------------DOSAGE FORMS AND STRENGTHS---------------------

AFLURIA^®, a sterile suspension for intramuscular injection, is supplied in two presentations:

• 0.5 mL preservative-free, single-dose, pre-filled syringe. (3)
• 5 mL multi-dose vial containing ten doses. Thimerosal, a mercury derivative, is added as a preservative; each 0.5 mL dose contains 24.5 micrograms (mcg) of mercury. (3)

Each 0.5 mL dose contains 15 mcg of influenza virus hemagglutinin (HA) from each of the three strains: A/Brisbane/59/2007, IVR-148 (H1N1), A/Uruguay/716/2007, NYMC X-175C (H3N2) (an A/Brisbane/10/2007-like strain), and B/Brisbane/60/2008. (3, 11)

-----------------------------CONTRAINDICATIONS----------------------------

• Hypersensitivity to eggs or chicken protein, neomycin, or polymyxin, or life-threatening reaction to previous influenza vaccination. (4)

------------------------WARNINGS AND PRECAUTIONS-------------------------

• If Guillain-Barré Syndrome (GBS) has occurred within 6 weeks of previous influenza vaccination, the decision to give AFLURIA^® should be based on careful consideration of the potential benefits and risks. (5.1)
• Immunocompromised persons may have a diminished immune response to AFLURIA^®. (5.2)

------------------------------ADVERSE REACTIONS----------------------------

The most common (= 10%) local (injection-site) adverse reactions were tenderness, pain, redness, and swelling. The most common (= 10%) systemic adverse reactions were headache, malaise, and muscle aches. (6)

To report SUSPECTED ADVERSE REACTIONS, contact CSL Biotherapies at 1-888-435-8633 or VAERS at 1-800-822-7967 and www.vaers.hhs.gov.

------------------------------DRUG INTERACTIONS----------------------------

• Do not mix with any other vaccine in the same syringe or vial. (7.1)
• Immunosuppressive therapies may diminish the immune response to AFLURIA^®. (7.2)

-----------------------USE IN SPECIFIC POPULATIONS---------------------

• Safety and effectiveness of AFLURIA^® have not been established in pregnant women or nursing mothers and in the pediatric population. (8.1, 8.3, 8.4)
• Antibody responses were lower in geriatric subjects than in younger subjects. (8.5)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 06/2009

____________________________________________________________________________________________________________________________________

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Prior to Administration

2.2 Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome (GBS)

5.2 Altered Immunocompetence

5.3 Preventing and Managing Allergic Reactions

5.4 Limitations of Vaccine Effectiveness

6 ADVERSE REACTIONS

6.1 Overall Adverse Reactions

6.2 Safety Experience from Clinical Studies

6.3 Postmarketing Experience

6.4 Other Adverse Reactions Associated With Influenza Vaccination

7 DRUG INTERACTIONS

7.1 Concurrent Use With Other Vaccines

7.2 Concurrent Use With Immunosuppressive Therapies

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed.

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

AFLURIA^® is an inactivated influenza virus vaccine indicated for active immunization of persons ages 18 years and older against influenza disease caused by influenza virus subtypes A and type B present in the vaccine.

This indication is based on the immune response elicited by AFLURIA^®; there have been no controlled clinical studies demonstrating a decrease in influenza disease after vaccination with AFLURIA^® (see Clinical Studies [14]).

2 DOSAGE AND ADMINISTRATION

2.1 Prior to Administration

AFLURIA^® should be inspected visually for particulate matter and discoloration prior to administration (see Description [11]), whenever suspension and container permit. If either of these conditions exists, the vaccine should not be administered. Any vaccine that has been frozen or is suspected of being frozen must not be used.

2.2 Administration

When using the preservative-free, single-dose syringe, shake the syringe thoroughly and administer the dose immediately.

When using the multi-dose vial, shake the vial thoroughly before withdrawing each dose, and administer the dose immediately. Between uses, store the vial at 2-8°C (36-46°F) (see How Supplied/Storage and Handling [16]). Once the stopper has been pierced, the vial must be discarded within 28 days.

AFLURIA^® should be administered as a single 0.5 mL intramuscular injection, preferably in the deltoid muscle of the upper arm.

3 DOSAGE FORMS AND STRENGTHS

AFLURIA^® is a sterile suspension for intramuscular injection. Each 0.5 mL dose contains 15 micrograms (mcg) of influenza virus hemagglutinin (HA) from each of the three influenza virus strains included in the vaccine (see Description [11]).

AFLURIA^® is supplied in two presentations:

• 0.5 mL preservative-free, single-dose, pre-filled syringe.
• 5 mL multi-dose vial containing ten doses. Thimerosal, a mercury derivative, is added as a preservative; each 0.5 mL dose contains 24.5 mcg of mercury.

4 CONTRAINDICATIONS

AFLURIA^® is contraindicated in individuals with known hypersensitivity to eggs or chicken protein, neomycin, or polymyxin, or in anyone who has had a life-threatening reaction to previous influenza vaccination.

5 WARNINGS AND PRECAUTIONS

5.1 Guillain-Barré Syndrome (GBS)

If GBS has occurred within 6 weeks of previous influenza vaccination, the decision to give AFLURIA^® should be based on careful consideration of the potential benefits and risks.

5.2 Altered Immunocompetence

If AFLURIA^® is administered to immunocompromised persons, including those receiving immunosuppressive therapy, the immune response may be diminished.

5.3 Preventing and Managing Allergic Reactions

Appropriate medical treatment and supervision must be available to manage possible anaphylactic reactions following administration of the vaccine.

5.4 Limitations of Vaccine Effectiveness

Vaccination with AFLURIA^® may not protect all individuals.

6 ADVERSE REACTIONS

6.1 Overall Adverse Reactions

Serious allergic reactions, including anaphylactic shock, have been observed during postmarketing surveillance in individuals receiving AFLURIA^®.

The most common local (injection-site) adverse reactions observed in clinical studies with AFLURIA^® were tenderness, pain, redness, and swelling. The most common systemic adverse reactions observed were headache, malaise, and muscle aches.

6.2 Safety Experience from Clinical Studies

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a vaccine cannot be directly compared to rates in the clinical studies of another vaccine and may not reflect the rates observed in clinical practice.

Clinical safety data for AFLURIA^® have been obtained in two clinical studies (see Clinical Studies [14]).

A US study (Study 1) included 1,357 subjects for safety analysis, ages 18 to less than 65 years, randomized to receive AFLURIA^® (1,089 subjects) or placebo (268 subjects) (see Clinical Studies [14] for study demographics). There were no deaths or serious adverse events reported in this study.

A UK study (Study 2) included 275 subjects, ages 65 years and older, randomized to receive preservative-free AFLURIA^® (206 subjects) or a European-licensed trivalent inactivated influenza vaccine as an active control (69 subjects) (see Clinical Studies [14]). There were no deaths or serious adverse events reported in this study.

The safety assessment was identical for the two studies. Local (injection-site) and systemic adverse events were solicited by completion of a symptom diary card for 5 days post-vaccination (Table 1). Unsolicited local and systemic adverse events were collected for 21 days post-vaccination (Table 2). These unsolicited adverse events were reported either spontaneously or when subjects were questioned about any changes in their health post-vaccination. All adverse events are presented regardless of any treatment causality assigned by study investigators.

Table 1: Proportion of Subjects With Solicited Local or Systemic Adverse Events^* Within 5 Days After Administration of AFLURIA^® or Placebo, Irrespective of Causality^†

		Study 1 Subjects = 18 to < 65 years				Study 2 Subjects = 65 years
Solicited Adverse event		AFLURIA®‡ n=1089		Placebo§ n=268		AFLURIA® n=206
Local
Tenderness¦		60%		18%		34%
Pain		40%		9%		9%
Redness		16%		8%		23%
Swelling		9%		1%		11%
Bruising		5%		1%		4%
Systemic
Headache		26%		26%		15%
Malaise		20%		19%		10%
Muscle aches		13%		9%		14%
Nausea		6%		9%		3%
Chills/ Shivering		3%		2%		7%
Fever = 37.7°C (99.86°F)		1%		1%		1%
Vomiting		1%		1%		0%

* In Study 1, 87% of solicited local and systemic adverse events were mild, 12% were moderate, and 1% were severe. In Study 2, 76.5% were mild, 20.5% were moderate, and 3% were severe. In both studies, most solicited local and systemic adverse events lasted no longer than 2 days.

† Values rounded to the nearest whole percent.

‡ Includes subjects who received either the single-dose (preservative-free) or multi-dose formulation of AFLURIA^®.

§ Thimerosal-containing placebo.

¦Tenderness defined as pain on touching.

Pain defined as spontaneously painful without touch.

Table 2: Adverse Events^* Reported Spontaneously by = 1% of Subjects Within 21 Days After Administration of AFLURIA^® or Placebo, Irrespective of Causality^†

		Study 1 Subjects = 18 to < 65 years				Study 2 Subjects = 65 years
Adverse Event		AFLURIA®‡ n=1089		Placebo§ n=268		AFLURIA® n=206
Headache		8%		6%		8%
Nasal Congestion		1%		1%		7%
Cough		1%		0.4%		5%
Rhinorrhea		1%		1%		5%
Pharyngolaryngeal Pain		3%		1%		5%
Reactogenicity Event		3%		3%		0%
Diarrhea		2%		3%		1%
Back Pain		2%		0.4%		2%
Upper Respiratory Tract Infection		2%		1%		0.5%
Viral Infection		0.4%		1%		0%
Lower Respiratory Tract Infection		0%		0%		1%
Myalgia		1%		1%		1%
Muscle Spasms		0.4%		1%		0%

* In Study 1, 63% of unsolicited adverse events were mild, 35% were moderate, and 2% were severe. In Study 2, 47% were mild, 51% were moderate, and 3% were severe. In both studies, most unsolicited adverse events lasted no longer than 5 days.

† Values greater than 0.5% rounded to the nearest whole percent.

‡ Includes subjects who received either the single-dose (preservative-free) or multi-dose formulation of AFLURIA^®.

§ Thimerosal-containing placebo.

6.3 Postmarketing Experience

Because postmarketing reporting of adverse reactions is voluntary and from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure. The adverse reactions described have been included in this section because they: 1) represent reactions that are known to occur following immunizations generally or influenza immunizations specifically; 2) are potentially serious; or 3) have been reported frequently. The following adverse reactions also include those identified during postapproval use of AFLURIA^® outside the US since 1985.

Blood and lymphatic system disorders

Transient thrombocytopenia

Immune system disorders

Allergic reactions including anaphylactic shock and serum sickness

Nervous system disorders

Neuralgia, paresthesia, and convulsions; encephalopathy, neuritis or neuropathy, transverse myelitis, and GBS

Vascular disorders

Vasculitis with transient renal involvement

Skin and subcutaneous tissue disorders

Pruritus, urticaria, and rash

General disorders and administration site conditions

Influenza-like illness (e.g., pyrexia, chills, headache, malaise, myalgia), injection-site inflammation (e.g., pain, erythema, swelling, warmth), and induration

6.4 Other Adverse Reactions Associated With Influenza Vaccination

Anaphylaxis has been reported after administration of AFLURIA^®. Although AFLURIA^® contains only a limited quantity of egg protein, this protein can induce immediate hypersensitivity reactions among persons who have severe egg allergy. Allergic reactions include hives, angioedema, allergic asthma, and systemic anaphylaxis (see Contraindications [4]).

The 1976 swine influenza vaccine was associated with an increased frequency of GBS. Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than one additional case per 1 million persons vaccinated.

Neurological disorders temporally associated with influenza vaccination, such as encephalopathy, optic neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy, have been reported.

Microscopic polyangiitis (vasculitis) has been reported temporally associated with influenza vaccination.

7 DRUG INTERACTIONS

7.1 Concurrent Use With Other Vaccines

There are no data to assess the concomitant administration of AFLURIA^® with other vaccines. If AFLURIA^® is to be given at the same time as another injectable vaccine(s), the vaccine(s) should be administered at different injection sites.

AFLURIA^® should not be mixed with any other vaccine in the same syringe or vial.

7.2 Concurrent Use With Immunosuppressive Therapies

The immunological response to AFLURIA^® may be diminished in individuals receiving corticosteroid or immunosuppressive therapies.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C: Animal reproduction studies have not been conducted with AFLURIA^®. It is also not known whether AFLURIA^® can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. AFLURIA^® should be given to a pregnant woman only if clearly needed.

8.3 Nursing Mothers

AFLURIA^® has not been evaluated in nursing mothers. It is not known whether AFLURIA^® is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when AFLURIA^® is administered to a nursing woman.

8.4 Pediatric Use

Safety and effectiveness in the pediatric population have not been established.

8.5 Geriatric Use

In four clinical studies, 343 subjects ages 65 years and older received AFLURIA^®. Hemagglutination-inhibiting (HI) antibody responses in geriatric subjects were lower after administration of AFLURIA^® in comparison to younger adult subjects (see Clinical Studies [14]). Adverse event rates were generally similar in frequency to those reported in subjects ages 18 to less than 65 years, although some differences were observed (see Adverse Reactions [6.2]).

11 DESCRIPTION

AFLURIA^®, Influenza Virus Vaccine for intramuscular injection, is a sterile, clear, colorless to slightly opalescent suspension with some sediment that resuspends upon shaking to form a homogeneous suspension. AFLURIA^® is prepared from influenza virus propagated in the allantoic fluid of embryonated chicken eggs. Following harvest, the virus is purified in a sucrose density gradient using a continuous flow zonal centrifuge. The purified virus is inactivated with beta-propiolactone, and the virus particles are disrupted using sodium taurodeoxycholate to produce a "split virion”. The disrupted virus is further purified and suspended in a phosphate buffered isotonic solution.

AFLURIA^® is standardized according to USPHS requirements for the 2009-2010 influenza season and is formulated to contain 45 mcg HA per 0.5 mL dose in the recommended ratio of 15 mcg HA for each of the three influenza strains recommended for the 2009-2010 Northern Hemisphere influenza season: A/Brisbane/59/2007, IVR-148 (H1N1), A/Uruguay/716/2007, NYMC X-175C (H3N2) (an A/Brisbane/10/2007-like strain), and B/Brisbane/60/2008.

The single-dose formulation is preservative-free; thimerosal, a mercury derivative, is not used in the manufacturing process for this formulation. The multi-dose formulation contains thimerosal, added as a preservative; each 0.5 mL dose contains 24.5 mcg of mercury.

A single 0.5 mL dose of AFLURIA^® contains sodium chloride (4.1 mg), monobasic sodium phosphate (80 mcg), dibasic sodium phosphate (300 mcg), monobasic potassium phosphate (20 mcg), potassium chloride (20 mcg), and calcium chloride (1.5 mcg). From the manufacturing process, each dose may also contain residual amounts of sodium taurodeoxycholate (= 10 ppm), ovalbumin (= 1 mcg), neomycin sulfate (= 0.2 picograms [pg]), polymyxin B (= 0.03 pg), and beta-propiolactone (< 25 nanograms).

The rubber tip cap and plunger used for the preservative-free, single-dose syringes and the rubber stoppers used for the multi-dose vial contain no latex.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Influenza illness and its complications follow infection with influenza viruses. Global surveillance of influenza identifies yearly antigenic variants. For example, since 1977 antigenic variants of influenza A (H1N1 and H3N2) and influenza B viruses have been in global circulation. Specific levels of HI antibody titers post-vaccination with inactivated influenza virus vaccine have not been correlated with protection from influenza virus. In some human studies, antibody titers of 1:40 or greater have been associated with protection from influenza illness in up to 50% of subjects.^1,2

Antibody against one influenza virus type or subtype confers limited or no protection against another. Furthermore, antibody to one antigenic variant of influenza virus might not protect against a new antigenic variant of the same type or subtype. Frequent development of antigenic variants through antigenic drift is the virologic basis for seasonal epidemics and the reason for the usual change to one or more new strains in each year’s influenza vaccine. Therefore, inactivated influenza vaccines are standardized to contain the HA of three strains (i.e., typically two type A and one type B) representing the influenza viruses likely to be circulating in the US during the upcoming winter.

Annual revaccination with the current vaccine is recommended because immunity declines during the year after vaccination and circulating strains of influenza virus change from year to year.³

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

AFLURIA^® has not been evaluated for carcinogenic or mutagenic potential or for impairment of fertility.

14 CLINICAL STUDIES

Three randomized, controlled clinical studies of AFLURIA^® have evaluated the immune responses (specifically, HI antibody titers) to each virus strain in the vaccine. In these studies, post-vaccination immunogenicity was evaluated on sera obtained 21 days after administration of AFLURIA^®. No controlled clinical studies demonstrating a decrease in influenza disease after vaccination with AFLURIA^® have been performed.

The US study (Study 1) was a randomized, double-blinded, placebo-controlled, multicenter study in healthy subjects ages 18 to less than 65 years. A total of 1,357 subjects were vaccinated (1,089 subjects with AFLURIA^® and 268 with a thimerosal-containing placebo). Subjects receiving AFLURIA^® were vaccinated using either a single-dose (preservative-free) or multi-dose (one of three lots) formulation. The evaluable efficacy population consisted of 1,341 subjects (1,077 in the AFLURIA^® group and 264 in the placebo group) with complete serological data who had not received any contraindicated medications before the post-vaccination immunogenicity assessment. Among the evaluable efficacy population receiving AFLURIA^®, 37.5% were men and 62.5% were women. The mean age of the entire evaluable population receiving AFLURIA^® was 38 years; 73% were ages 18 to less than 50 years and 27% were ages 50 to less than 65 years. Additionally, 81% of AFLURIA^® recipients were White, 12% Black, and 6% Asian.

In Study 1, the following co-primary immunogenicity endpoints were assessed: 1) the lower bounds of the 2-sided 95% confidence intervals (CI) for the proportion of subjects with HI antibody titers of 1:40 or greater after vaccination, which should exceed 70% for each vaccine antigen strain; and 2) the lower bounds of the 2-sided 95% CI for rates of seroconversion (defined as a 4-fold increase in post-vaccination HI antibody titers from pre-vaccination titers of 1:10 or greater, or an increase in titers from less than 1:10 to 1:40 or greater), which should exceed 40% for each vaccine antigen strain.

In subjects ages 18 to less than 65 years, serum HI antibody responses to AFLURIA^® met the pre-specified co-primary endpoint criteria for all three virus strains (Table 3). Clinical lot-to-lot consistency was demonstrated for the single-dose (preservative-free) and multi-dose formulations of AFLURIA^®, showing that these formulations elicited similar immune responses.

Table 3: Study 1 – Serum HI Antibody Responses in Subjects = 18 to < 65 Years Receiving AFLURIA^®

Treatment Arm		Number Enrolled/ Evaluable		Vaccine Strain		Seroconversion Rate* (95% CI)		HI Titer = 1:40† (95% CI)
All active AFLURIA® influenza vaccine formulations‡		1089/1077		H1N1		48.7% (45.6, 51.7)		97.8% (96.7, 98.6)
				H3N2		71.5% (68.7, 74.2)		99.9% (99.5, 100.0)
				B		69.7% (66.9, 72.5)		94.2% (92.7, 95.6)
Placebo		270/264		H1N1		2.3% (0.8, 4.9)		74.6% (68.9, 79.8)
				H3N2		0.0% (N/A)		72.0% (66.1, 77.3)
				B		0.4% (< 0.1, 2.1)		47.0% (40.8, 53.2)

* Seroconversion rate is defined as a 4-fold increase in post-vaccination HI antibody titer from pre-vaccination titer = 1:10, or an increase in titer from < 1:10 to = 1:40. Lower bound of 95% CI for seroconversion should be > 40% for the study population.

† HI titer = 1:40 is defined as the proportion of subjects with a minimum post-vaccination HI antibody titer of 1:40. Lower bound of 95% CI for HI antibody titer = 1:40 should be > 70% for the study population.

‡ Active formulations include aggregated results for the single-dose (preservative-free) and multi-dose formulations of AFLURIA^®.

The UK study (Study 2) was a randomized, controlled study that enrolled 275 healthy subjects ages 65 years and older. This study compared AFLURIA^® with a European-licensed trivalent inactivated influenza vaccine as an active control. The evaluable efficacy population consisted of 274 subjects (206 in the AFLURIA^® group and 68 in the control group). Among these subjects, 50% were men and 50% were women, with a mean age of 72 years (range: 65 to 93 years).

The co-primary immunogenicity endpoints for the seroconversion rate and the proportion of subjects with a minimum post-vaccination HI antibody titer of 1:40 are presented in Table 4.

Table 4: Study 2 – Serum HI Antibody Responses in Subjects = 65 Years Receiving AFLURIA^®

Number of Subjects		Vaccine Strain		Seroconversion Rate* (95% CI)		HI Titer = 1:40† (95% CI)
206		H1N1		34.0% (27.5, 40.9)		85.0% (79.3, 89.5)
		H3N2		44.2% (37.3, 51.2)		99.5% (97.3, 100.0)
		B		45.6% (38.7, 52.7)		77.7% (71.4, 83.2)

* Seroconversion rate is defined as a 4-fold increase in post-vaccination HI antibody titer from pre-vaccination titer = 1:10, or an increase in titer from < 1:10 to = 1:40. Lower bound of 95% CI for seroconversion should be > 30% for the study population.

† HI titer = 1:40 is defined as the proportion of subjects with a minimum post-vaccination HI antibody titer of 1:40. Lower bound of 95% CI for HI antibody titer = 1:40 should be > 60% for the study population.

A second UK study (Study 3) was a randomized, controlled study that enrolled 406 healthy subjects ages 18 years and older (stratified by age from 18 to less than 60 years and 60 years and older). This study compared AFLURIA^® with a European-licensed trivalent inactivated influenza vaccine as an active control. In a post-hoc analysis of different age ranges, among subjects ages 18 to less than 65 years receiving AFLURIA^® (146 subjects), 47% were men and 53% were women, with a mean age of 48 years for all subjects. Among subjects ages 65 years and older receiving AFLURIA^® (60 subjects), 53% were men and 47% were women, with a mean age of 71 years.

The post-hoc analysis of serum HI antibody responses showed that the lower bound of the 95% CI for subjects with HI antibody titers of 1:40 or greater after vaccination exceeded 70% for each strain. HI antibody responses were lower in subjects ages 65 years and older after administration of AFLURIA^®. Serum HI antibody responses to the active control were similar to those for AFLURIA^® in both age groups.

15 REFERENCES

1. Hannoun C, Megas F, Piercy J. Immunogenicity and protective efficacy of influenza vaccination. Virus Res 2004;103:133-138.

2. Hobson D, Curry RL, Beare AS, et al. The role of serum hemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses. J Hyg Camb 1972;70:767-777.

3. Centers for Disease Control and Prevention. Prevention and Control of Influenza: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2007;56 (RR-6):1-53.

16 HOW SUPPLIED/STORAGE AND HANDLING

AFLURIA^® is supplied as a 0.5 mL preservative-free, single-dose, pre-filled syringe (packaged without needles) and as a 5 mL multi-dose vial containing ten 0.5 mL doses, with thimerosal, a mercury derivative, added as a preservative; each 0.5 mL dose contains 24.5 mcg of mercury.

Product Description		NDC Number
Package of ten 0.5 mL preservative-free, prefilled syringes		33332-009-01
5 mL multi-dose vial		33332-109-10

Store refrigerated at 2-8°C (36-46°F). Do not freeze. Protect from light. Do not use AFLURIA^® beyond the expiration date printed on the label.

17 PATIENT COUNSELING INFORMATION

• Inform the patient that AFLURIA^® is an inactivated vaccine that cannot cause influenza but stimulates the immune system to produce antibodies that protect against influenza. The full effect of the vaccine is generally achieved approximately 3 weeks after vaccination. Annual revaccination is recommended.
• Instruct the patient to report any severe or unusual adverse reactions to their healthcare provider.

Manufactured by:

CSL Limited

Parkville, Victoria, 3052, Australia

US License No. 1764

Distributed by:

CSL Biotherapies Inc.

King of Prussia, PA 19406 USA

AFLURIA is a registered trademark of CSL Limited.

CSL Limited – Confidential

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