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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.

Janssen Ad26. RSV. preF Vaccine Description for 2022

Janssen Ad26. RSV. preF Vaccine uses its innovative vaccine technology platform®. This technology is based on the development and production of adenoviral vectors (for transfer of hereditary material) which can activate the immune system to stimulate immunity against the virus.

According to the CDC, Respiratory Syncytial Virus Infection (RSV) was discovered in 1956 and has since been recognized as one of the most common causes of childhood illness. It causes annual outbreaks of respiratory illnesses in all age groups. In most regions of the United States, RSV usually circulates during fall, winter, and spring, but the timing and severity of RSV season in a given community can vary from year to year. 

Although most children will be infected by RSV within the first year of life, adults are also susceptible to the virus. Usually, the illness is mild however some adults may have severe symptoms consistent with a lower respiratory tract infection, such as pneumonia. 

Janssen Ad26. RSV. preF Vaccine has been tested in several clinical trials with older adults. Positive results from the Phase 2b CYPRESS study have led to the initiation of a Phase 3 EVERGREEN study.  

Janssen Ad26. RSV. preF Vaccine Indication

Janssen Ad26. RSV. preF Vaccine candidate is indicated to prevent illness from RSV.

Janssen Ad26. RSV. preF Vaccine News 2021- 2022

September 29, 2021 - "Positive data from our first RSV vaccine efficacy study and the initiation of the Phase 3 EVERGREEN study are crucial milestones in the clinical development of our investigational RSV adult vaccine, which has the potential to safely and effectively prevent lower respiratory tract disease caused by RSV in older adults," says Penny Heaton, M.D., Global Therapeutic Area Head, Vaccines, Janssen Research & Development, LLC.

January 5, 2021 - The Journal of Infectious Diseases published the results of a Phase 2 study. Ad26.RSV.preF demonstrated protection from RSV infection through immunization in a human challenge model and, therefore could potentially protect against natural RSV infection and disease.

Janssen Ad26. RSV. preF Vaccine Clinical Trials

Janssen Ad26. RSV. preF Vaccine has been studied in many clinical trials.

A phase 3 trial is in the process of recruiting 1,113 adults 18 to 59 years of age who are healthy or at risk for severe Respiratory Syncytial Virus (RSV) disease, compared to adults 65 years and above.

Shingles (Herpes Zoster) Vaccines 2026

Herpes Zoster, also known as shingles, is a vaccine-preventable disease caused by the varicella-zoster virus (VZV), which also causes chickenpox, according to the U.S. Centers for Disease Control and Prevention (CDC). The U.S. Food and Drug Administration (FDA) approved shingles vaccines for use in accordance with the updated 2025 schedules. The European Medicines Agency (EMA) approves various shingles vaccines in over 30 countries. As of 2026, the shingles vaccination market exceeds $2 billion in annual revenue.

Shingles Vaccines Approved

Shingrix—GSK's Shingrix is a non-live, adjuvanted recombinant shingles (zoster) vaccine containing the varicella-zoster virus glycoprotein E antigen and the AS01B adjuvant system, a proprietary formulation containing QS-21 and MPL in liposomes.

Zostavax is Merck's live, attenuated varicella-zoster virus (a weakened form of the chickenpox virus) vaccine. According to the U.S. CDC, the zoster vaccine can be administered concurrently with all other live and inactivated vaccines, including those routinely recommended for people 60 or older.

SK bioscience's SKYZoster™ is a live varicella-zoster virus vaccine that attenuates the virus. SKYZoster was approved in South Korea by the Ministry of Food and Drug Safety in September 2017.

SINOVAC's live attenuated varicella vaccine, a WHO-prequalified Chinese varicella vaccine, was successfully delivered to the Republic of Türkiye in 2023 and is registered in Lebanon and Kenya.

Shingles Vaccine Candidates

Curevo Vaccine's Amezosvatein (CRV-101) is an adjuvanted subunit shingles vaccine candidate designed to maximize cellular-mediated immunity (CMI) protection by combining the gE protein antigen with our proprietary adjuvant. On January 7, 2024, Curevo announced positive data from a Phase 2 trial of Amezosvatein, head-to-head versus Shingrix, in participants aged 50 and older. There were zero confirmed cases of herpes zoster (shingles) among participants in the amezosvatein arm. On October 16, 2024, the Company announced that Amezosvatein met all primary endpoints in the randomized, active-controlled, and observer-blind Phase 2 trial. On January 13, 2025, the Company announced positive updated immunogenicity and safety data from its 876-patient Phase 2 trial of amezosvatein (CRV-101) compared to Shingrix in participants aged 50 years and older. Based upon these results, Curevo will advance amezosvatein into global Phase 3 trials in 2025. On March 17, 2025, Curevo Vaccine announced the closing of a $110 million Series B round to advance the development of amezosvatein.

BioNTech SE initiated a randomized, controlled, dose-selection Phase 1/2 clinical trial of BNT167 in February 2023. The trial evaluates the safety, tolerability, and immunogenicity of mRNA vaccine candidates against shingles.

Jiangsu Recbio Technology Co., Ltd. announced on December 29, 2023, that REC610 is equipped with a novel adjuvant BFA01 independently developed by the Company, which can promote the production of high levels of VZV glycoprotein E (gE)-specific CD4+T cells and antibodies. On December 19, 2022, it received approval from the Philippines FDA to conduct a randomized, observer-blinded, phase I clinical trial. The Interim Analysis results published on December 29, 2023, showed that REC610 demonstrated an overall favorable safety and tolerability profile in healthy participants aged 40 and above after two vaccination doses. REC610 induced strong gE-specific humoral and cellular immune responses, evident after the first vaccination and peaked 30 days after the second vaccination.

Immorna announced on January 9, 2023, that the U.S. FDA cleared its investigational new drug application to conduct a Phase 1 multi-center study of JCXH-105, a self-replicating RNA vaccine against Shingles. Additionally, on May 30, 2023, the Company announced that the first subject had been dosed in its First-In-Human (FIH) Phase 1 multi-center study of JCXH-105.

Dynavax's Z-1018 is an investigational vaccine candidate being developed to prevent shingles in adults aged 50 and older. In the fourth quarter of 2024, the Company completed enrollment in the phase 1/2 trial, and Dynavax anticipates reporting top-line immunogenicity and safety data in the third quarter of 2025.

Shingles Vaccination and Dementia

On April 23, 2025, a study published in JAMA found evidence that herpes zoster vaccination reduces the risk of dementia, a finding more likely to be causal than the associations reported in existing correlational evidence. On April 2, 2025, Nature published a study - A natural experiment on the effect of herpes zoster vaccination on dementia - that provides evidence of a dementia-preventing or dementia-delaying effect from zoster vaccination that is less vulnerable to confounding and bias than the existing associational evidence. The journal BMC Public Health published results from a study on October 2, 2023. The study concluded that the zoster vaccine for the prevention of shingles/herpes zoster and the influenza vaccine to prevent influenza were associated with a diminished risk of dementia, with the zoster association appearing more pronounced. A non-peer-reviewed study published on May 25, 2023, reported that shingles vaccinations were associated with a 19.9% lower risk of dementia.

Shingles Vaccination and Cardiovascular Events

A study published in the European Heart Journal in May 2025 shows a 23% lower risk of cardiovascular events in recipients of the shingles vaccine in the 8 years following vaccination. These findings suggest that live zoster vaccination may help reduce the burden of cardiovascular disease in the general population.

Alzheimer's Disease Vaccine and Monoclonal Antibody 2024

As of June 14, 2024, the U.S. Food and Drug Administration (FDA), the European Medicines Agency (EMA), Japan, and the United Kingdom's NHS have not authorized preventive Alzheimer's disease (AD) vaccines or approved therapeutics for bipolar disorder (BD), major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). In the United States, the CDC says about 4% of people over 65 years of age have Dementia. Recently, monoclonal antibody intravenous infusion therapies (Leqembi® and Aduhelm®) have been approved in the U.S. and Japan to treat, not prevent, early AD, a degenerative brain disease.

Alzheimer's Vaccine Candidates 2024

AADvac1 is a therapeutic vaccine candidate for Alzheimer's disease that targets misfolded tau protein, a common denominator of neurofibrillary pathology.

ACI-35.030 is a first-in-class AD vaccine candidate designed to generate a specific antibody response against pTau proteins in the brain. AC Immune is collaborating with Janssen Pharmaceuticals, Inc. Recent results show that ACI-35.030 treatment rapidly leads to the strong and durable induction of antibodies specific for pathological forms of Tau, such as pTau and its aggregated form, ePHF. In addition, the ACI-35.030-induced antibody response was sustained and could be periodically boosted over 72 weeks. 

Alzamend Neuro, Inc.'s AL001 novel lithium-delivery system can potentially deliver the benefits of marketed lithium salts while mitigating or avoiding currently experienced toxicities associated with lithium. AL001 is designed to distribute lithium in the brain, resulting in lower exposure to other body organs and an improved safety profile compared to currently marketed lithium salts. Alzamend Neuro announced in October 2023 the receipt of a "Study May Proceed" letter from the U.S. FDA for the initiation of study AL001-BD01, a Phase IIA clinical study of AL001 for BD type 1. On March 22, 2023, the Company announced the completion of the clinical portion of its Phase IIA multiple ascending dose study. On November 20, 2023, the Company announced a receipt of a "Study May Proceed" letter from the FDA for the initiation of study AL001-MDD01, a Phase IIA clinical study of AL001 for treating patients with MDD. On December 11, 2023, the Company received a "Study May Proceed" letter from the FDA for the initiation of study AL001-PTSD01, a Phase IIA clinical study of AL001 for treating patients with PTSD. On May 9, 2024, the Company announced a stock offering for $25,000,000.

Alzinova AB's ALZ101 is an active, therapeutic oligomer-specific vaccine candidate that stimulates the production of antibodies against the toxic Aβ oligomers. The first-in-human Phase 1b study in patients with early AD was initiated in 2021. Alzamend is also pursuing AL001 for the treatment of bipolar disorder and PTSD. Topline data for the analysis is anticipated in the second half of 2023. In addition, the Company partnered with the Miller School of Medicine and the Interdisciplinary Stem Cell Institute at the University of Miami in Florida for its Phase I/IIA clinical trial of ALZN002.

Araclon Biotech's ABvac40 is an active vaccine against the Aβ40 peptide for treating patients with early-stage Alzheimer's disease. On October 25, 2023, the Company reported a phase 2 trial met primary endpoints, confirming the vaccine's safety, tolerability, and robust immune response against the Aβ40 peptide in early-stage Alzheimer's patients. ABvac40 treatment slowed disease progression up to 38% compared with placebo as measured by the Mini-Mental State Examination score.

Alzheimer's Monoclonal Antibody Treatments

Aduhelm™ is an amyloid beta-directed antibody injection of 100 mg/mL for intravenous use indicated to treat AD and was approved by the FDA on July 8, 2021. The FDA issued approval to Biogen and Eisai Co., Ltd. 

Leqembi™ gained U.S. FDA traditional approval for treating AD l on July 6, 2023. The approval of Leqembi (BAN2401, lecanemab-irmb) was granted to Eisai R&D Management Co., Ltd. On September 25, 2023, Japan issued a similar authorization, as did China on January 9, 2024.

Eli Lilly's donanemab (Kisunla™) was approved in July 2024 for a broad population of people diagnosed with mild cognitive impairment due to Alzheimer’s. The total cost of Kisunla will vary by patient based on when they complete treatment. A JAMA Original Investigation published positive study results in 2023.

Gantenerumab is a fully human IgG1 antibody that binds with subnanomolar affinity to a conformational epitope on Aβ fibrils. It encompasses both N-terminal and central amino acids of Aβ. A November 2023 study found that Gantenerumab led to a lower amyloid plaque burden among persons with early AD than placebo at 116 weeks. Still, it was not associated with slower clinical decline. (GRADUATE I and II; NCT03444870 and NCT03443973. In 2021, Gantenerumab was granted U.S. FDA Breakthrough Therapy Designation in Alzheimer's Disease.

ACI-24.060 is an amyloid-beta (Abeta) antibody produced by AC Immune SA and derived from the Company's SupraAntigen®  platform. The FDA awarded Fast Track destination on June 27, 2023. On May 13, 2024, AC Immune and Takeda announced a partnership.

ADvantage Therapeutics, Inc. announced that the UK's MHRA had granted AD04™ an Innovation Passport for treating AD under the Innovative Licensing and Access Pathway on April 5, 2023. Authorities in Poland, Bulgaria, and Slovakia approved its Clinical Trial Application on June 20, 2023, to conduct a clinical trial with AD04. The Company believes AD04™ may function as an immunomodulator, stimulating and/or regulating the immune system to reduce AD pathology. Rather than being limited to a specific aspect of AD pathology, such as amyloid beta or tau, AD04™ may restore the expression of genes in lipid metabolism, improve phagocytosis, and reduce inflammation. On November 27, 2023, the Company announced the first patient enrolled in AD04's European Phase 2b clinical trial.

ProMIS therapeutic product candidate PMN310 is a monoclonal therapeutic antibody designed to treat AD, consisting of an AβO conformational peptide epitope conjugated to KLH as a carrier protein to provide T cell help, elicited robust and sustained antibody responses with either alum or QS-21 as the adjuvants.

UB-311 is a synthetic, peptide-based active immunotherapy candidate targeting toxic forms of aggregated beta-amyloid in the brain to treat and prevent Alzheimer's disease. Phase 1, Phase 2a, and Phase 2a long-term extension trials have shown UB-311 to be well tolerated in mild-to-moderate AD patients over three years of repeat dosing, with a safety profile comparable to placebo and no cases of amyloid-related imaging abnormalities-edema in the Phase 2a trial. It was granted U.S. FDA Fast Track status.

Alzheimer's Treatments

Eli Lilly and Company presented an interim analysis from a phase 1 study of LY3372993 on March 31, 2023. Remternetug (LY3372993) is an IgG1 monoclonal antibody directed at the pyroglutamate modification of the third amino acid of the amyloid-beta peptide that is present only in brain amyloid plaques. This antibody demonstrated rapid and robust amyloid plaque reduction in participants with AD. The safety, tolerability, and pharmacokinetic/pharmacodynamic data support the ongoing Phase 3 trial (NCT05463731)

Alzamend Neuro, Inc.'s AL001 is a patented ionic cocrystal technology that delivers a therapeutic combination of lithium, proline, and salicylate to treat Alzheimer's and other neurodegenerative diseases and psychiatric disorders. ALZN002 immunotherapy is intended to treat patients diagnosed with Alzheimer's by inducing their antibodies. These are targeted to remove the Aβ1‑42 protein, reducing the deposition of amyloid plaque in the brain and thereby reducing the progression of disease-associated clinical signs and symptoms. The Company partnered with Biorasi as its contract research organization.

Prothena Corporation's PRX012 is a next-generation, high-binding potency antibody designed to enable subcutaneous dosing on a patient-friendly, convenient administration schedule, potentially providing greater accessibility for AD patients and caregivers. Accordingly, the U.S. FDA granted Fast Track Designation on April 26, 2022.

Synaptogenix, Inc.'s Bryostatin-1 is targeting Alzheimer's disease. The paper "Advanced Alzheimer's Disease Patients Show Safe, Significant, and Persistent Benefit in 6-Month Bryostatin Trial" concluded that the Bryostatin-treated MMSE 10-14 patients showed no significant cognitive decline throughout the 10-month trial. In contrast, the placebo patients declined by -12.8 SIB points.

BCG Vaccination and Dementia

An Original Investigation led by investigators at Massachusetts General Hospital and Brigham and Women's Hospital was published by The JAMA Network on May 19, 2023, concluding that BCG vaccination was associated with a lower rate and risk of Alzheimer's disease and related Dementia. In a risks analysis, the BCG vaccine was associated with a lower risk of Alzheimer's disease and related dementias (ADRD) (5-year risk difference, −0.011; 95% CI, −0.019 to −0.003) and a decreased risk of death in patients without an earlier diagnosis of ADRD (5-year risk difference, −0.056; 95% CI, −0.075 to −0.037).

Alzheimer's Testing

Researchers at Karolinska Institutet announced on April 12, 2023, that a type of sugar molecule in the blood is associated with the level of Tau. This protein plays a critical role in the development of severe Dementia. Therefore, bisecting N-acetylglucosamine and Tau are valuable blood biomarkers for predicting AD. The U.S. FDA permitted marketing on May 4, 2022, for Fujirebio Diagnostics, Inc. Lumipulse G β-Amyloid Ratio (1-42/1-40) in vitro diagnostic test intended to be used in adult patients aged 55 years and older, presenting with cognitive impairment who are being evaluated for AD and other causes of cognitive decline.

On December 27, 2022, a new study, Brain-derived Tau: a novel blood-based biomarker for Alzheimer's disease-type neurodegeneration, presented a novel blood test that assessed brain-derived Tau-detected Alzheimer' s-related neurodegeneration and differentiated Alzheimer's from other neurodegenerative diseases. Furthermore, this innovative test outperformed total Tau and, unlike neurofilament light, showed specificity to Alzheimer's disease-type neurodegeneration. Thus, brain-derived Tau demonstrates the potential to complete the AT(N) scheme in blood and will be used in evaluating.

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