Merck Announces VAXNEUVANCEtm (Pneumococcal 15-valent Conjugate Vaccine) Met Key Immunogenicity and Safety Endpoints in Phase 3 Pivotal Trial Evaluating Use in Infants, PNEU-PED (V114-029)

Merck (NYSE: MRK), known as MSD outside the United States and Canada, today announced topline results from the pivotal PNEU-PED (V114-029) study evaluating the immunogenicity, safety and tolerability of VAXNEUVANCEtm (Pneumococcal 15-valent Conjugate Vaccine) in healthy infants enrolled between 42-90 days of age (n=1720). In the trial, infants were given a 4-dose regimen of either VAXNEUVANCE or the licensed 13-valent pneumococcal conjugate vaccine (PCV13) at 2, 4, 6, and 12-15 months of age.

In the PNEU-PED study, primary endpoints demonstrated:

• VAXNEUVANCE had a safety profile generally comparable to PCV13 following receipt of any vaccine dose.
• At 30 days following the third dose in the series (PD3), VAXNEUVANCE was non-inferior to PCV13 for all 13 shared serotypes based on serotype-specific response rates (proportions of individuals achieving the accepted immunoglobulin G (IgG) threshold value of 0.35mcg/mL) and for 12 of the 13 shared serotypes based on serotype-specific IgG geometric mean concentrations (GMCs).
  • The lower bounds of the two-sided 95 percent confidence intervals (CI) for the serotype-specific IgG GMC ratios were greater than 0.5 for 12 shared serotypes; the lower bound was 0.48 for serotype 6A, narrowly missing non-inferiority criteria.
• At 30 days following the fourth (toddler) dose (PD4), VAXNEUVANCE was non-inferior to PCV13 for all 13 shared serotypes based on serotype-specific IgG GMCs.

Secondary endpoints demonstrated statistically superior immune responses for VAXNEUVANCE in comparison to PCV13 for shared serotype 3 and unique serotypes 22F and 33F based on prespecified criteria, as well as non-inferior immune responses to antigens contained in several routinely used pediatric vaccines when administered concomitantly with VAXNEUVANCE or PCV13.

"By nature, pneumococcal disease is constantly evolving. Strains of the disease associated with invasiveness cause significant disease burden in children, calling for innovation to help protect this vulnerable population worldwide," said Dr. Roy Baynes, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. "At Merck, our goal is to design pneumococcal vaccines that target strains causing the greatest proportion of disease while maintaining a strong immune response to these serotypes. With the inclusion of serotypes 22F and 33F, VAXNEUVANCE has the potential to play an important role in the prevention of invasive pneumococcal disease in children."

In PNEU-LINK (V114-031), a Phase 3 study to evaluate the safety and tolerability of VAXNEUVANCE in healthy infants, VAXNEUVANCE was generally well-tolerated with a safety profile generally comparable to PCV13 in healthy infants enrolled at 42-90 days of age (n=2409). Full results from the PNEU-PED and PNEU-LINK studies will be presented at an upcoming scientific congress.

There are 100 different types of pneumococcal bacteria, which can affect children differently than adults. Children under the age of 2 are particularly vulnerable to pneumococcal infection, and incidence of invasive pneumococcal disease remains highest in the first year of life. Certain pneumococcal serotypes continue to put children at risk, including serotypes 22F, 33F and 3, which represent more than a quarter of all cases of invasive pneumococcal disease in children under the age of 5.

The VAXNEUVANCE Phase 3 clinical development program is comprised of 16 trials investigating the safety, tolerability and immunogenicity of VAXNEUVANCE in a variety of populations who are at increased risk for pneumococcal disease, including 10 that investigated VAXNEUVANCE for use in children and infants.

On July 16, 2021, the U.S. Food and Drug Administration (FDA) approved VAXNEUVANCE for adults 18 years of age and older for active immunization for the prevention of invasive disease caused by the 15 S. pneumoniae serotypes contained in the vaccine. Plans are on track for submission of a supplemental regulatory licensure application to the FDA for use in children before the end of the year.

About PNEU-PED

PNEU-PED is a Phase 3, multicenter, randomized, double-blind, active-comparator-controlled study evaluating the safety, tolerability and immunogenicity of a 4-dose regimen of VAXNEUVANCE in healthy infants enrolled at 42-90 days of age (n=1720).

In the primary analysis, participants were randomized to receive VAXNEUVANCE or PCV13. Immune responses for the 13 shared serotypes contained in VAXNEUVANCE and PCV13 were measured at 30 days post-dose three (PD3) and post-dose four (PD4). Immune responses were assessed based on anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin G (IgG) response rates at 30 days PD3 and geometric mean concentrations (GMCs) at 30 days PD3 and PD4.

In the secondary analysis, antibody responses to select licensed pediatric vaccines were evaluated when administered concomitantly with VAXNEUVANCE or PCV13. Additionally, immune responses for serotypes 22F and 33F, the two serotypes unique to VANXNEUVANCE, were assessed based on anti-PnPs serotype-specific IgG response rates at 30 days PD3 and PD4, and immune responses for serotype 3 were assessed based on anti-PnPs serotype-specific IgG response rates at 30 days PD3 and IgG GMCs 30 days PD3 and PD4.

Safety analyses were performed in the All-Participants-As-Treated (APaT) population, defined as all randomized participants who received at least one dose of study vaccination.

About PNEU-LINK

PNEU-LINK is a Phase 3, multicenter, randomized, double-blind active-comparator-controlled study evaluating the safety and tolerability of VAXNEUVANCE in healthy infants enrolled at 42-90 days of age (n=2409).

In the primary analysis, healthy infants were randomized to receive either VAXNEUVANCE or PCV13. Safety analyses were performed on the All-Participants-As-Treated (APaT) population, defined as all randomized participants who received at least one dose of study vaccination.

About VAXNEUVANCE (Pneumococcal 15-valent Conjugate Vaccine)

VAXNEUVANCE, Merck's 15-valent pneumococcal conjugate vaccine, consists of purified capsular polysaccharides from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F individually conjugated to CRM197 carrier protein. VAXNEUVANCE is indicated for active immunization of adults 18 years of age and older for the prevention of invasive disease caused by the S. pneumoniae serotypes contained in the vaccine. It is currently under investigation in the pediatric population. VAXNEUVANCE previously received Breakthrough Therapy designation from the FDA for the prevention of invasive pneumococcal disease in pediatric patients 6 weeks to 18 years of age.

Merck is involved in litigation challenging the validity of several Pfizer Inc. patents that relate to pneumococcal vaccine technology in the United States and several foreign jurisdictions.

Select Safety Information for VAXNEUVANCE in Adults 18 Years of Age and Older

Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (e.g., anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid.

Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE.

The most commonly reported solicited adverse reactions in individuals 18 through 49 years of age were: injection site pain (75.8%), fatigue (34.3%), myalgia (28.8%), headache (26.5%), injection site swelling (21.7%), injection site erythema (15.1%) and arthralgia (12.7%).

The most commonly reported solicited adverse reactions in individuals 50 years of age and older were: injection site pain (66.8%), myalgia (26.9%), fatigue (21.5%), headache (18.9%), injection site swelling (15.4%), injection site erythema (10.9%) and arthralgia (7.7%).

Vaccination with VAXNEUVANCE may not protect all vaccine recipients.

Merck's Commitment to Infectious Diseases

For more than 100 years, Merck has contributed to the discovery and development of novel medicines and vaccines to combat infectious diseases. In addition to a combined portfolio of vaccines and antibacterial, antiviral and antifungal medicines, Merck has multiple programs that span discovery through late-stage development. To learn more about Merck's infectious diseases pipeline, visit www.merck.com.

About Merck

For 130 years, Merck, known as MSD outside of the United States and Canada, has been inventing for life, bringing forward medicines and vaccines for many of the world's most challenging diseases in pursuit of our mission to save and improve lives. We demonstrate our commitment to patients and population health by increasing access to health care through far-reaching policies, programs and partnerships. Today, Merck continues to be at the forefront of research to prevent and treat diseases that threaten people and animals ? including cancer, infectious diseases such as HIV and Ebola, and emerging animal diseases ? as we aspire to be the premier research-intensive biopharmaceutical company in the world. For more information, visit www.merck.com and connect with us on Twitter, Facebook, Instagram, YouTube and LinkedIn.

Forward-Looking Statement of Merck & Co., Inc., Kenilworth, N.J., USA

This news release of Merck & Co., Inc., Kenilworth, N.J., USA (the "company") includes "forward-looking statements" within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of the company's management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of the global outbreak of novel coronavirus disease (COVID-19); the impact of pharmaceutical industry regulation and health care legislation in the United States and internationally; global trends toward health care cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; the company's ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of the company's patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

The company undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in the company's 2020 Annual Report on Form 10-K and the company's other filings with the Securities and Exchange Commission (SEC) available at the SEC's Internet site (www.sec.gov).

Please see Prescribing Information for VAXNEUVANCE (pneumococcal 15-valent conjugate vaccine) at https://www.merck.com/product/usa/pi_circulars/v/vaxneuvance/vaxneuvance_pi.pdf and Patient Information at https://www.merck.com/product/usa/pi_circulars/v/vaxneuvance/vaxneuvance_ppi.pdf.