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CAPVAXIVE® Pneumococcal 21-valent Conjugate Vaccine Clinical Trials, Dosage, Indication, Side Effects

Merck's CAPVAXIVE® (V116) (Pneumococcal 21-valent Conjugate Vaccine (PVC21) prevents invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults. CAPVAXIVE addresses the serotypes that create adult pneumococcal disease, including eight unique serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B. CAPVAXIVE utilizes the PeliCRM197® carrier protein, which helps enhance antigen immunogenicity in conjugate vaccines.

On June 17, 2024, the U.S. Food and Drug Administration (FDA) approved CAPVAXIVE (STN: BLA 125814/0), a vaccine specifically designed for adults, covering serotypes responsible for approximately 84% of invasive pneumococcal disease in adults 50 years and older. Across four Phase 3 studies, CAPVAXIVE demonstrated robust immune responses in vaccine-naïve and vaccine-experienced adult populations. CAPVAXIVE was approved in Canada in July 2024 and in Australia in January 2025.

On January 30, 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) recommended the approval of CAPVAXIVE for adults 18 and older. On March 26, 2025, Merck announced that the EMA approved CAPVAXIE in all 27 European Union (EU) member states, including Iceland, Liechtenstein, and Norway.

On October 16, 2024, key findings from the STRIDE-8 trial included: CAPVAXIVE was immunogenic for all 21 serotypes included in the vaccine, as measured by serotype-specific OPA geometric mean titers (GMTs) (primary immunogenicity objective) and immunoglobulin G geometric mean concentrations (GMCs) (secondary immunogenicity objective) at Day 30; Immune responses elicited by CAPVAXIVE were comparable to PCV15 followed by PPSV23 for the 13 common serotypes and higher for the eight serotypes unique to CAPVAXIVE, as measured by serotype-specific OPA GMTs and IgG GMCs 30 days post-vaccination; The proportions of participants with adverse events (AEs), including injection-site, systemic, and vaccine-related AEs, were numerically lower in the V116 + placebo group than in the PCV15 + PPSV23 group.

Merck, known as MSD outside the United States and Canada, is united around a purpose: We use the power of cutting-edge science to save and improve lives worldwide. For more than four decades, Merck has been at the forefront of pneumococcal disease prevention through vaccination and remains committed to protecting people of all ages from this disease.

CAPVAXIVE Vaccine U.S. CDC ACIP

The U.S. Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) Work Group decided on October 23, 2024, to lower the age-based recommendation to include adults 50-64 years. The ACIP met on June 27, 2024, and reviewed these presentations: Economic analysis and public health impact of PCV21 use in adults, Mr. C Stoecker; Summary of three economic studies on the use of 21-valent pneumococcal conjugate vaccine (PCV21) among adults in the U.S.; Andrew J. Leidner, PhD; Summary of WG Interpretation of EtR and policy options on PCV21 use in adults and clinical guidance for implementation, Dr. M Kobayashi on February 29, 2024. Heather Platt, M.D., presented Key Results from the Phase 3 Clinical Development Program, which include, but are not limited to the following: V116 elicits robust immune responses to all 21 serotypes contained in the vaccine; is noninferior to PCV20 for all common serotypes and superior to PCV20 for 10 of 11 serotypes unique to V116 in pneumococcal vaccine-naïve adults ≥50 years of age; is immunogenic in pneumococcal vaccine experienced adults, regardless of the prior vaccine received; is immunogenic when administered concomitantly with inactivated influenza vaccine; and V116 is well-tolerated with a safety profile generally comparable to currently licensed pneumococcal vaccines. The initial assessment by the ACIP Work Group suggested that V116 provides broader serotype coverage than currently recommended vaccines for adults aged 65 and older or immunocompromised adults. Miwako Kobayashi, M.D., presented the Work Group's proposed policy questions on lowering the age-based recommendation for pneumococcal vaccination to include adults aged 50-64. The ACIP is expected to vote in an upcoming meeting on whether V116 should be recommended as a pneumococcal vaccination option for U.S. adults. CDC recommendations follow FDA approval.

CAPVAXIVE Vaccine Indication

V116 is designed to be administered as a single dose to help prevent invasive pneumococcal disease and pneumonia in adults. Over 150,000 adults are hospitalized with pneumococcal pneumonia each year in the U.S. The serotypes covered by V116 are responsible for approximately 83% of invasive pneumococcal disease in individuals 65 and older. Pneumococcal disease is an infection caused by the bacterium Streptococcus pneumoniae. There are more than 100 types (serotypes) of pneumococcal bacteria.

CAPVAXIVEV Vaccine Availability

As of 2025, CAPVAXIVE has been approved by the U.S. FDA (STN: BL 125814/0) and approved in Canada, Australia, and Europe.

CAPVAXIVE V116 Vaccine News

April 24, 2025 - Merck announced that CAPVAXIVEW produced $107 million in sales, representing continued uptake since its launch in the U.S. in the third quarter of 2024.

March 26, 2025 - Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories, stated, "We are proud to bring CAPVAXIVE to adults in Europe who may benefit from its broad protection and are eager to continue working with regulatory authorities to expand CAPVAXIVE availability worldwide."

January 31, 2025—Dr. Paula Annunziato, senior vice president of infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories, commented in a press release, "This positive opinion is yet another testament to the clinical profile of CAPVAXIVE and brings us a step closer to helping protect adults in the EU against pneumococcal disease. Invasive pneumococcal disease can lead to serious consequences, including hospitalization, organ damage, and even death. We are pleased with the CHMP recommendation and look forward to the European Commission's decision."

October 16, 2024 - "Adults with chronic medical conditions, such as kidney disease or diabetes, are particularly vulnerable to invasive pneumococcal disease, which may increase their risk of severe illness," said Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health and pediatrics at Emory University and member of Merck's Scientific Advisory Committee.

June 21, 2024 - Nature published a news brief - FDA approves 21-valent pneumococcal vaccine.

June 17, 2024: Dr. Walter Orenstein, professor emeritus of medicine, epidemiology, global health, and pediatrics at Emory University and member of Merck's Scientific Advisory Committee, stated, "CAPVAXIVE is designed to include the serotypes that cause the majority of invasive pneumococcal disease in adults, helping to protect them against invasive pneumococcal disease and pneumococcal pneumonia."

March 19, 2024 - "The extensive data presented this week reaffirms our confidence in the potential clinical value V116 could provide to a range of adult populations," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories, in a press release. "We are encouraged by the results of these studies showing that V116 has generated immune responses to the serotypes responsible for most adult invasive pneumococcal disease."

February 29, 2024 - James Loehr, MD, led a U.S. CDC vaccine committee review of V116.

July 28, 2022 - Merck presented positive results from the Phase 1/2 study for V116, Merck's investigational Pneumococcal 21-Valent Conjugate Vaccine designed to target serotypes that account for 85% of all invasive pneumococcal diseases in U.S. adults 65 years and older as of 2019, and enrolled the first patient into the Phase 3 STRIDE-3 trial evaluating V116 in vaccine-naïve adults. V116 contains eight serotypes not included in any currently licensed pneumococcal vaccine.

June 21, 2022 - Merck announced the presentation of positive results from the Phase 1/2 study, V116-001, evaluating the safety, tolerability, and immunogenicity of V116, the company's investigational 21-valent PCV, in pneumococcal vaccine-naïve adults 18-49 years of age (Phase 1) and 50 years of age and older (Phase 2).

April 14, 2022 - V116, Merck's investigational 21-valent pneumococcal conjugate vaccine, received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the prevention of IPD and pneumococcal pneumonia caused by Streptococcus pneumoniae serotypes 3, 6A/C, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15B/C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, 35B in adults 18 years of age and older.

V116 Vaccine Clinical Trials

Merck's 21-valent PCV has been in clinical trials since 2019. Multiple Phase 3 trials of V116 were initiated within the last 12 months, including STRIDE-3 (NCT05425732), STRIDE-6 (NCT05420961), STRIDE-7 (NCT05393037), STRIDE-4 (NCT05464420), STRIDE-5 (NCT05526716), and STRIDE-8 (NCT05696080).

On March 19, 2024, Merck announced across the clinical studies presented at the 13th Meeting of the International Society of Pneumonia and Pneumococcal Diseases, V116 was shown to be immunogenic for all 21 serotypes covered by the vaccine in a variety of adult populations, including those who had not previously received a pneumococcal vaccine (pneumococcal vaccine-naïve), those who had previously received a pneumococcal vaccine (pneumococcal vaccine-experienced) and those with an increased risk of pneumococcal disease, including people living with HIV. V116 also elicited higher immune responses than the studied comparators for the serotypes unique to V116 in all STRIDE studies presented at this meeting. In addition to Phase 3 clinical data on V116, Merck also presented preliminary data from the real-world evidence study ((Abstract #308)) on March 19, 2024, Pneumococcal Pneumonia Epidemiology, Urine Serotyping, and Mental Outcomes (PNEUMO), which found that among 2,065 adults 50 years of age and older hospitalized with community-acquired pneumonia between 2018 and 2022, 242 pneumococcal serotypes were detected. Of these serotypes, approximately 84% were covered by V116. About 25% of the detected serotypes were covered only by V116, not PCV15 or PCV20.

Data from STRIDE-3 Sub-group (Abstract #379) - The sub-group analysis of the pivotal STRIDE-3 (NCT05425732) trial evaluated immunogenicity in adults 50 years of age and older who had not previously received a pneumococcal vaccine (Cohort 1) by age groups (50–64, 65–74 and 75–84 years) (n=2,362). Results found that V116 was immunogenic for all 21 vaccine serotypes across the studied age sub-groups, as assessed by serotype-specific OPA GMTs 30 days post-vaccination. There was a slight downward trend in immune responses among adults aged 65–74 and those 75 years and older, compared to adults in other age groups. V116 had a safety profile comparable to PCV20. Results from the STRIDE-3 trial were presented at the World Vaccine Congress West Coast in November 2023.

Data from STRIDE-6 and the STRIDE-6 Sub-group (Abstracts #353 and #520) - STRIDE-6 (NCT05420961) is a Phase 3 trial investigating V116 in adults 50 years of age and older who had previously received a pneumococcal vaccine at least one year prior (n = 712). Participants were enrolled based on previous pneumococcal vaccination with PPSV23, PCV15, PCV13 (pneumococcal 13-valent conjugate vaccine), PPSV23+PCV13, PCV13+PPSV23 or PCV15+PPSV23, and received either V116, PCV15 or PPSV23.

Results showed that V116 was immunogenic across all cohorts, as assessed by OPA GMTs 30 days post-vaccination, and that V116 elicited comparable immune responses to the serotypes also covered by PCV15 and PPSV23, as well as higher immune responses for the serotypes covered only by V116. A STRIDE-6 sub-group analysis evaluating immunogenicity across all cohorts by time since prior pneumococcal vaccination found that V116 elicited comparable immune responses regardless of time since prior pneumococcal vaccination, including more than ten years post-vaccination with PPSV23 (n=56), and 5–9 years post-vaccination with either PPSV23 or other pneumococcal vaccines (n=208). In this study, V116 had a safety profile comparable to PCV15 and PPSV23.

Data from STRIDE-7 (Abstract #1093) - STRIDE-7 (NCT05393037) is a Phase 3, double-blind study of V116 in adults living with HIV (n=304). Results showed that V116 was immunogenic for all serotypes covered by the vaccine, as assessed by OPA GMTs and IgG GMCs 30 days post-vaccination. V116 elicited comparable immune responses to the comparator, PCV15+PPSV23, for all 13 shared serotypes and higher immune responses for the eight serotypes covered only by V116. Fewer participants experienced adverse events (AEs) with V116 (71.6%) compared with PCV15+PPSV23 (91%), primarily due to fewer injection-site AEs.

Data from STRIDE-9 (Abstract #1085) - STRIDE-9 (NCT05633992) is a Phase 3, randomized, double-blind, active-comparator-controlled study that investigated V116 in Japanese adults aged 65 years and older who had not previously received a pneumococcal vaccine (n = 450). Serotype-specific OPA responses were measured at baseline and 30 days post-vaccination, and the results demonstrated that V116 elicited non-inferior immune reactions for the 12 serotypes shared with PPSV23 and serotype 15B (which is included in PPSV23 but not in V116). V116 also elicited higher immune responses for the serotypes covered only by V116 and not by PPSV23. V116 also had a comparable safety profile to PPSV23.

Data from PNEUMO U.S. Serotype Distribution Study (Abstract #308) - The PNEUMO U.S. study evaluated pneumococcal serotype distribution among adults 50 years of age and older hospitalized with community-acquired pneumonia (n=2,065), one of the non-invasive forms of pneumococcal disease, between 2018 and 2022 in three hospitals in Tennessee and Georgia. Urine samples from patients were evaluated for antigens from 30 pneumococcal serotypes using novel serotype-specific urinary antigen detection (SSUAD) assays (all serotypes in PCV15, PCV20, and V116 are included except 15B). Among the 242 serotypes detected by SSUAD assays, approximately 84% were covered by V116, compared to approximately 64% covered by PCV20. One-fourth (approximately 25%) of the detected serotypes were covered by V116 only and not by PCV15 or PCV20.

Additional Clinical Study Results Presented at ISPPD (Abstract #382 and #355) - Data from Phase 3 clinical studies STRIDE-4 (NCT05464420) and STRIDE-5 (NCT05526716) were also presented at ISPPD.

SKYCovione™ COVID-19 Vaccine

SK bioscience SKYCovione™ (SKYCovion™, GBP510) is a recombinant protein-based vaccine made of proteins that form tiny particles studded with fragments of the pandemic SARS-CoV-2 coronavirus. These nanoparticles were designed by scientists at the University of Washington School of Medicine (UW of Medicine) and advanced into clinical trials by SK bioscience and  GlaxoSmithKline (GSK) with financial support from the Coalition for Epidemic Preparedness Innovations. In addition, SKYCovione includes GSK's pandemic adjuvant, AS03, which helps strengthen the immune response to the vaccine.

The vaccine consists of GBP510 with the AS03 adjuvant. GBP510 is a self-assembling two-component protein nanoparticle that displays 60 copies of the receptor-binding domain (RBD) of SARS-CoV-2 Spike. The nanoparticle component allows for the high-level multimeric display of the RBD antigen that enhances humoral immune responses even at lower doses. This platform also allows for efficient and straightforward adjustment of the vaccine to match variant strains of SARS-CoV-2 or other emergent pathogens by swapping out the target antigen displayed by the nanoparticle. In addition, the inclusion of AS03 may enable the use of lower doses of the protein antigen.

The Phase 3 clinical trial results showed that SKYCovion induced neutralizing antibody responses and had an acceptable safety and reactogenicity profile compared to the control vaccine, Vaxzevria™, used in the study. In addition, the extended phase I/II clinical trials showed a high immune response to the Omicron variant after a booster of SKYCovion. The clinical trial was conducted at 16 institutions, including the Korea National Institute of Health Vaccine Center, the International Vaccine Institute, and Korea University Guro Hospital.

The Korean Ministry of Food and Drug Safety approved SKYCovione for use on June 29, 2022, in individuals 18 years and older. In addition, the South Korean government has agreed to purchase 10 million doses for domestic use. On May 30, 2023, the UK's Medicines and Healthcare products Regulatory Agency (MHRA) granted Marketing Authorization for SK bioscience's COVID-19 vaccine SKYCovion™ as a primary series for strong immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older. On June 19, 2023, SkyCovione received an Emergency Use Listing (EUL) from the World Health Organization (WHO). SKYCovione is the 12th COVID-19 vaccine granted an EUL by the WHO.

SKYCovion is the world's first vaccine developed using the RoseTTAFold, a software tool that uses deep learning to quickly and accurately predict protein structures from limited information. The RoseTTAFold was designed as a three-track neural network developed by the University of Washington.

SK bioscience is an innovative biopharmaceutical company committed to global pandemic preparedness through vaccine development and manufacturing to create more equitable access to vaccines.

SKYCovione Indication

SKYCovione is indicated to prevent the disease COVID-19 caused by the SARS-CoV-2 virus. When a person is given the vaccine, their immune system is expected to identify the nanoparticles containing parts of the spike protein as foreign and produce natural defenses - antibodies and T cells - against them. If, later on, the vaccinated person comes into contact with SARS-CoV-2, the immune system will recognize the spike protein on the virus and be prepared to attack it. The antibodies and immune cells can protect against COVID-19 by working together to kill the virus, prevent its entry into the body's cells, and destroy infected cells.

"This intramuscular vaccine was designed at the molecular level to present the immune system with a key part of the coronavirus spike protein. We know this part, called the receptor-binding domain, is targeted by the most potent antibodies," said Neil King, an assistant professor of biochemistry at UW Medicine and co-developer of the vaccine.

SKYCovion Booster

SK bioscience announced that SKYCovione had shown cross-neutralizing activity against Omicron variant BA.1 following booster vaccination administered ~7 months after the primary series. The results of the Phase I/II clinical trial, conducted with 81 healthy adults who received a booster dose of SKYCovione 7 months after the second dose of SKYCovione™, showed that the neutralizing antibody titers against the Omicron variant BA.1 were 25 times the titers right after the second dose, and 72 times the titers seven months after the second dose. 

SKYCovione News

June 19, 2023 - Jaeyong Ahn, CEO of SK bioscience said, "Based on the immunogenicity and safety profile, SKYCovione has become the first Korean vaccine to be granted to the WHO EUL. We will be committed to developing more vaccines to strengthen Korea's vaccine sovereignty and enable equitable access to the vaccine."

May 30, 2023 - Jaeyong Ahn, CEO of SK bioscience said in a press release, "We are delighted with the MHRA's authorization of Korea's first COVID-19 vaccine SKYCovion. This is the result of our commitment to protecting and promoting global public health. We are confident it will be the milestone to solidify our position in the global market amid the transition of the pandemic to the endemic phase."

August 18, 2022 - The EMA's human medicines committee began reviewing a conditional marketing authorization application for Skycovion, a vaccine to protect against COVID-19.

August 1, 2022 - SK bioscience announced that it had applied for a Conditional Marketing Authorization for SKYCovion to the European Medicines Agency.

July 29, 2022 - SK bioscience announced that it applied for a Conditional Marketing Authorization of the SKYCovion to the UK Medicines and Healthcare Products Regulatory Authority.

June 29, 2022 - The Seattle scientists behind the new vaccine sought to create a 'second-generation' COVID-19 vaccine that is safe, effective at low doses, simple to manufacture, and stable without deep freezing. These attributes could enable vaccination on a global scale by reaching people in areas with limited medical, transportation, and storage resources.

SKYCovione Clinical Trials

A Phase 3 clinical trial, Immunogenicity and Safety Study of SK SARS-CoV-2 Recombinant Nanoparticle Vaccine (GBP510) Adjuvanted With AS03 (COVID-19), compared the immunogenicity and safety of SKYCovione recombinant nanoparticle vaccine adjuvanted with AS03 (GBP510) to the Oxford/AstraZeneca vaccine Covishield/Vaxzevria in adults aged 18 years and older. The results indicated that SKYCovione elicits roughly three times more neutralizing antibodies than the Oxford/AstraZeneca vaccine Covishield/Vaxzevria. In these studies, SKYCovione or Covishield/Vaxzevria was administered twice with an interval of four weeks. In the Phase 3 trial, there were again no severe adverse reactions to the vaccine.

Phase 1/2 trial results announced by SK bioscience last November and posted as a preprint found that SKYCovione was safe and produced virus-neutralizing antibodies in all trial participants receiving the adjuvanted vaccine. 

TPOXX® (Tecovirimat) Clinical Trials, Dosage, Efficacy, Side Effects

SIGA Technologies, Inc. TPOXX® (tecovirimat, ST-246®, TEPOXX), a novel small-molecule oral drug that inhibits the variola virus's and other poxviruses' viral maturation by preventing the formation of a secondary viral envelope (protein VP13) found on the surface of all orthopoxviruses. Without this envelope, viral particles remain inside the cell and cannot spread to and infect other cells. Tecovirimat is 77-82% bound to human plasma proteins. Tecovirimat is an inducer of cytochrome P450 (CYP) 3A and a weak inhibitor of CYP2C8 and CYP2C19. However, the effects are not expected to be clinically relevant for most substrates of those enzymes based on the magnitude of interactions and the duration of treatment of TPOXX. 

Tecovirimat's efficacy for treating smallpox was established based on data from the U.S. Food and Drug Administration (FDA) Animal Rule and safety data from 359 healthy adults. TPOXX has been approved by the FDA, Canada, the U.K., and the European Medicines Agency (EMA) for the treatment of smallpox as of July 13, 2018. In January 2022, the EMA and the U.K. approved Tecovirimat with a broader label that covers the treatment of smallpox, mpox, cowpox, and complications from vaccination for smallpox. On May 30, 2022, the World Health Organization (WHO) confirmed that TPOXX was effective against mpox infections. On January 2, 2025, tecovirimat was approved in Japan for the treatment of orthopoxviruses.

On April 16, 2025, a study funded by the National Institute of Allergy and Infectious Diseases and others determined that tecovirimat did not reduce the number of days to lesion resolution in patients with mpox caused by clade I MPXV.

On December 10, 2024, the U.S. National Institutes of Health (NIH) announced tecovirimat did not reduce the time to lesion resolution or have an effect on pain among adults with mild to moderate clade II mpox and a low risk of developing severe disease, according to an interim data analysis from the international clinical trial called the Study of Tecovirimat for Mpox (STOMP). Given the lack of an efficacy signal, clinical trials have been discontinued. The STOMP findings are consistent with results reported in 2024 from a National Institute of Allergy and Infectious Diseases (NIAID)-cosponsored randomized controlled trial of tecovirimat among children and adults with clade I mpox in the Democratic Republic of the Congo. On August 15, 2024, the  NIAID   announced topline results from a preliminary analysis of the PALM 007 (Tecovirimat for Treatment of Monkeypox Virus) phase 2 clinical trial (NCT05559099). NIAID reported that the study did not meet its primary endpoint of a statistically significant improvement in time to lesion resolution within 28 days post-randomization for patients in the Democratic Republic of the Congo with mpox who were administered tecovirimat. 

As of September 17, 2024, the U.S. Centers for Disease Control and Prevention (CDC) recommends tecovirimat as the first-line antiviral treatment for severe mpox or for individuals with mpox who are at risk for severe disease. Tecovirimat is FDA-approved only for the treatment of smallpox in adults and children. Using tecovirimat to treat other orthopoxvirus infections, including mpox, is unapproved. On June 9, 2023, the CDC recommended that postexposure prophylaxis be considered for all household members, including children and infants, when mpox is diagnosed. However, the safety and efficacy of TPOXX for treating mpox have not been established. The CDC published Guidance for Tecovirimat Use Under Expanded Access Investigational New Drug Protocol on September 15, 2022. The CDC/FDA expanded TPOXX access via the Investigational New Drug Protocol. Its use follows Informed Consent. The FDA  suggested that the broad use of TPOXX could promote resistance and render the drug ineffective for some patients. The CDC hosted a COCA call on October 6, 2022, and presented a situational update for Clinicians about severe mpox virus infections. The CDC Health Alert Network (HAN) issued CDCHAN-00481 on November 17, 2022, providing clinicians and public health officials with information on managing mpox in patients requiring therapeutics. TPOXX treatment for mpox is available through voluntary participation in https://www.stomptpoxx.org/stompsites, sponsored by the U.S. NIH.

Tecovirimat - NDC Code(s): 50072-200-42. DrugBank Accession Number: DB12020. UNII: F925RR824R. ATC code: J05AX24. KEGG: D09390, as monohydrate: D11557. ChEMBL: ChEMBL1257073. Formula: C19H15F3N2O3. ND No. 116,039, CDC IRB No. 6402.

SIGA Technologies, Inc. (NASDAQ: SIGA) is a commercial-stage pharmaceutical company based in New York (31 East 62nd Street, 10065).

TPOXX Sales And Deliveries

SIGA established a network with over 20 partners across discovery, pre-clinical, clinical, manufacturing, and supply chains that supported the development of TPOXX and the successful delivery of approximately $200 million of courses to the U.S. Strategic National Stockpile (SNS). On July 22, 2024, the U.S. Department of Health and Human Services exercised a procurement option to deliver approximately $113 million of oral TPOXX treatment courses.

On June 17, 2024, SIGA announced an agreement to expand access to TPOXX to the member states in the Association of Southeast Asian Nations. On April 1, 2024, SIGA Technologies announced that it had entered into an amendment to its international promotion agreement with Meridian Medical Technologies, Inc. Effective June 1, 2024, SIGA will drive international promotion activities for oral TPOXX, while maintaining its contractual relationship with Meridian to ensure continuity for key customer relationships.

In 2023, SIGA had $131 million in product sales, including approximately $98 million of fourth quarter product sales of oral TPOXX to the U.S. SNS, roughly $11 million of product sales of oral TPOXX to the U.S. DoD, of which approximately $6 million was recognized in the fourth quarter; and approximately $21 million of international sales, of which roughly $12 million was recognized in the fourth quarter. In the first two months of 2024, the Company delivered an additional approximately $15 million of oral TPOXX to the U.S. SNS, substantially completing the oral TPOXX order received in July 2023, as well as offered an additional roughly $7 million of oral TPOXX to European countries and Canada.

On August 9, 2022, SIGA Technologies announced the exercise of procurement options under its 75A50118C00019 (19C) contract with the U.S. Department of Health and Human Services (HHS) to deliver intravenous (IV) formulations of TPOXX treatment courses, valued at approximately $26 million. Product deliveries of IV TPOXX in connection with these contract options are targeted for 2023. September 29, 2022, SIGA Technologies announced that the U.S. DoD awarded a new contract for the procurement of $10.7 million of oral TPOXX (Contract number: W911SR22C0051), of which $5.1 million of oral TPOXX is targeted for delivery in 2022. The remainder is subject to an option at the sole discretion of the DoD. This contract follows an award made earlier this year for the procurement of $7.4 million of oral TPOXX (Contract Number: W911SR22C0032), under which all products are expected to be delivered in 2022.

In September 2018, SIGA signed a contract with the U.S. Biomedical Advanced Research and Development Authority (BARDA) for additional procurement and development related to oral and intravenous formulations of TPOXX. SIGA has also collaborated with the Department of Defence (DoD) Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense (JPEO-CBRND) to develop the post-exposure prophylaxis (PEP) indication for TPOXX. The DoD has drafted an Expanded Access Protocol (EAP) for TPOXX, which can be used for post-exposure prophylaxis (PEP) purposes for certain DoD-affiliated personnel. In addition, oral TPOXX is supplied to the Canadian Department of National Defence and the Public Health Agency of Canada for stockpiling as an essential countermeasure.

TPOXX Mpox Effectiveness and Breakthrough Infections

Data from 15 clinical trials of oral TPOXX in over 800 healthy volunteers, including a pivotal repeat-dose phase 1 pharmacokinetics (PK) trial involving 20 healthy volunteers conducted in Japan. These studies showed no drug-related serious adverse events and quantifiable PK within efficacious dose ranges. 

A small study published in January 2024 suggested that early tecovirimat initiation may hasten subjective symptomatic improvement in people with severe mpox. However, more extensive randomized trials are needed to evaluate this finding. The Antimicrobial Agents Chemotherapy journal published a letter on June 20, 2023, identifying Tecovirimat Resistance-Associated Mutations in Human Monkeypox Virus in Los Angeles County. This analysis detected TPOXX resistance-related HIV status.

The U.S. CDC published "Notes from the Field" on April 28, 2023, describing patients in New York City who were diagnosed with mpox and also developed new lesions after completing tecovirimat treatment, suggesting that post-treatment lesions may occur more commonly than previously reported by the CDC. In addition, the CDC reported on September 9, 2022, among 317 patients with available outcome information, 230 (72.6%) recovered with or without sequelae by or before completion of the post-treatment assessment; 87 (27.4%) patients were reported by clinicians to be not yet recovered, 78 of whom had not yet completed the standard 14-day tecovirimat treatment course. The CDC's MMWR was published on September 9, 2022. At the post-treatment follow-up visit, it was confirmed that three (2.2%) of 137 persons with available information had developed new lesions, compared with 25 (13.1%) who had developed new lesions during the first week of treatment. Most (119, 89.5%) patients reported that all lesions were crusted and healing with a new layer of skin under the scab following treatment. 

TPOXX, Mpox, and HIV

JAMA Internal Medicine published a study on January 8, 2024, demonstrating that people with HIV (PWH) who received tecovirimat within seven days of mpox symptom onset were 13 times less likely to progress to severe mpox disease compared with those who were treated after seven days or who did not receive tecovirimat. These researchers wrote that the findings of this study support the use of tecovirimat in all people with HIV (PWH) as soon as mpox is suspected. In a U.S. NIH-funded retrospective study published on May 2, 2023, a cohort of New York City patients treated with tecovirimat for severe mpox, HIV status did not appear to affect treatment outcomes. As of March 3, 2023, the STOMP Trial is evaluating the use of TPOXX in the HIV community. 

TPOXX Tecovirimat Resistance

On November 19, 2023, the U.S. CDC's Emerging Infectious Diseases - Volume 29, Number 12—December 2023 - confirmed that the MPXV F13L gene homologue encodes the target of tecovirimat, and single amino acid changes in F13 are known to cause resistance to tecovirimat. Genomic sequencing identified 11 mutations previously reported to cause resistance, as well as 13 novel mutations. The resistant phenotype was determined using a viral cytopathic effect assay. We tested 124 isolates from 68 patients; 96 isolates from 46 patients were found to have a resistant phenotype. Most resistant isolates were associated with severely immunocompromised mpox patients on multiple courses of tecovirimat treatment. In contrast, most isolates identified by routine surveillance of patients not treated with tecovirimat remained sensitive. 

This Annals of Internal Medicine report (July 2023) - Tecovirimat Resistance in an Immunocompromised Patient With Mpox and Prolonged Viral Shedding - confirms the potential rapid selection of a resistant mutant virus during tecovirimat monotherapy, and we believe this report is the first to study this phenomenon longitudinally. A variant (VP37 N267D) with substantiated tecovirimat resistance was selected within the standard 2-week treatment.

TPOXX Ingredients

Tecovirimat Formula: C19H15F3N2O3; ChemSpider ID: 17281586; ChEMBL Id: 1257073; PubChem CID: 16124688; Monoisotopic mass376.103485 Da. The capsules include the inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. The capsule shell consists of gelatin, FD&C Blue #1, FD&C Red #3, FD&C Yellow #6, and titanium dioxide.

TPOXX For Children

The U.S. CDC's MMWR on June 9, 2023 - Notes from the Field: Exposures to Mpox Among Cases in Children Aged ≤12 Years — United States, September 25–December 31, 2022- When caring for the child with mpox, postexposure prophylaxis should be considered for all members of the household. On August 4, 2022, the CDC confirmed that no clinical studies had been conducted in pediatric populations regarding the use of TPOXX.

TPOXX For Women

On May 18, 2023, the CDC confirmed a lack of sufficient data on TPOXX in women. However, on January 6, 2023, a CDC Morbidity and Mortality Weekly Report disclosed that four pregnant women were hospitalized for mpox and administered tecovirimat, which was tolerated with no adverse reactions.

TPOXX Side Effects

The JAMA Network published a Research Letter on August 22, 2022: Compassionate Use of Tecovirimat for Treating Monkeypox Infection. In this preliminary, limited study, oral tecovirimat was well tolerated by all patients with mpox infection, with minimal adverse effects. The safety of TPOXX was evaluated in three clinical trials in 359 healthy adult subjects aged 18-79 years. Of the subjects who received at least one 600 mg dose of TPOXX, 59% were female, 69% were White, 28% were Black/African American, 1% were Asian, and 12% were Hispanic or Latino. Ten percent of the study participants were aged 65 or older. Of these 359 subjects, 336 received at least 23 of 28 doses of 600 mg TPOXX twice daily for 14 days. The most frequently reported adverse reactions were headaches and nausea. Adverse reactions occurred in at least 2% of the subjects in the TPOXX treatment group. In addition, co-administration of repaglinide and tecovirimat may cause mild to moderate hypoglycemia.

TPOXX Drug Interactions

Significant interactions have been reported in healthy adults with co-administration of repaglinide (hypoglycemia) and midazolam (decreased effectiveness of midazolam).

TPOXX Price

The U.S. CDC confirmed on August 18, 2022, that healthcare providers could provide tecovirimat (TPOXX) treatment to patients with mpox under EA-IND. The drug is currently offered at no cost. Contact the CDC Emergency Operations Center (770-488-7100) for clinical consultation on patient cases. NYC providers who want to prescribe tecovirimat and adhere to the IND protocol can email [email protected] for information on free delivery to patients or request supplies for a pharmacy at their facility.

TPOXX News

January 2, 2025 -  SIGA Technologies received regulatory approval in Japan for treating smallpox, mpox, and cowpox, as well as complications following smallpox vaccination in adults and pediatric patients weighing at least 13 kg.

March 13, 2024 - "In 2023, SIGA had approximately $131 million in product revenues and approximately $84 million of pre-tax operating income," stated Diem Nguyen, Chief Executive Officer. "These financial results represent a significant increase over the 2022 financial results; product revenues increased 51% over the corresponding 2022 amount, and pre-tax operating income increased 96% over the corresponding 2022 amount.

April 28, 2023—The U.S. CDC published Notes from the Field: Post-treatment Lesions After Tecovirimat Treatment for Mpox—New York City, August–September 2022. New lesions appeared a median of 13 days after completion of Tecovirimat treatment (range = 2–30 days). In eight patients, the provider rated post-treatment lesions as less severe than initial lesions (median severity score = 3 [range = 3–7]). 

February 2, 2023 - Special Report: Overview of the regulatory approval of tecovirimat intravenous formulation for treating smallpox: potential impact on smallpox outbreak response capabilities, and future tecovirimat development potential.

September 6, 2022—The HHS Administration for Strategic Preparedness and Response awarded AmerisourceBergen a distribution contract valued at $19.8 million to expand MPXV treatment access.

August 25, 2022 - The Swiss government health agency (SwissMedic) intends to purchase 500 units of the TPOXX antiviral. 

July 15, 2022 - SIGA Technologies announced a collaboration with KaliVir Immunotherapeutics to make TPOXX® available for use with KaliVir's novel oncolytic vaccinia immunotherapy platform, including multiple proprietary genetic modifications that can be combined to generate a unique oncolytic virus that has been optimized for systemic delivery and anti-tumor immune stimulation.

May 19, 2022 - SIGA Technologies, Inc. announced that the U.S. FDA approved the IV formulation of TPOXX for treating smallpox.

January 10, 2022 - SIGA Technologies, Inc. announced that the EMA approved SIGA's Marketing Authorisation Application for oral tecovirimat. The EMA approval includes labeling for oral tecovirimat, indicating its use to treat smallpox, mpox, cowpox, and vaccinia complications following vaccination against smallpox.

July 29, 2021 - SIGA Technologies, Inc. announced that it has partnered with Oxford University in the U.K. to provide TPOXX® (tecovirimat) under an expanded access protocol to treat individuals affected by mpox in the Central African Republic.

July 13, 2018 - The U.S. FDA approved TPOXX (tecovirimat), the first drug with an indication for the treatment of smallpox. The FDA granted this application Fast Track and Priority Review designations, and TPOXX also received an Orphan Drug designation.

TPOXX Clinical Trials

The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, is sponsoring the Study of Tecovirimat for Human Mpox Virus (STOMP). The STOMP trial assesses whether tecovirimat is safe and effective for treating mpox in people with the disease.

A Phase 3 clinical trial evaluating the antiviral tecovirimat, also known as TPOXX, began enrolling adults and children with monkeypox infection in the United States on September 9, 2022. Study investigators aim to register more than 500 people from clinical research sites nationwide. Interested volunteers can visit the ACTG website (clinical trial A5418) for more information. The National Institute of Allergy and Infectious Diseases sponsors the trialThe first study compares the enrolled participants' immune response to the Jynneos smallpox vaccines to the immune response to Jynneos while on TPOXX treatment. In addition, the study is designed to determine if TPOXX interferes with developing an effective immune response to the vaccine. A second clinical study, also expected to commence in 2022, will look at creating an expanded safety dataset to support 28-day dosing of TPOXX for the post-exposure prophylaxis indication compared with the currently approved 14 days for treatment of smallpox indication.