Self-Amplifying mRNA Vaccine KOSTAIVE® side effects collection status

Post-marketing survey 4th interim report (4 months from the start of sales)

Feb 26, 2025

In February 2025, Meiji Seika Pharma released a post-marketing survey 4th interim report of self-amplifying mRNA vaccine "KOSTAIVE®." Meiji Seika Pharma is a Japanease licensee of KOSTAIVE® developed by Arcturus Therapeutic.

According to the report,

Among the adverse events collected during the four months following the launch of this drug, 1067 events due to 365 cases (of which 3 were fatal), could not be ruled out as causally related to the drug (Table 1). Among these, severe adverse reactions accounted for 10 events due to 8 cases, all of which were unknown adverse reactions that could not be predicted from the precautions in the electronic package insert. As the post-marketing surveillance progresses, the number of collected cases is increasing.

Below is a list of adverse events.

◆Gastrointestinal Disorders

Malice, Diarrhea, Toothache, Loose stools, White stools, Abdominal pain, Abdominal Discomfort, Vomiting

◆General Disorders And Administration Site Conditions

Chills, Abnormal sensation, Chest pain, Fatigue, Dry mouth, Death, Injection site itching, Injection site induration, Injection site erythema, Injection site swelling, Injection site bleeding, Heat at injection site, Injection site pain, Fever, Pain

◆Infectious And Parasitic Diseases

Aspiration pneumonia, Oral herpes, Nasopharyngeal inflammation, Urinary tract infection, Cystitis

◆Hepatobiliary System Disorder

Liver dysfunction

◆Musculoskeletal And Connective Tissue Disorders

Joint pain, Musculoskeletal discomfort, Muscle pain, Muscle weakness, Back pain

◆Blood And Lymphatic System Disorders

Lymphadenopathy

◆Respiratory, Thoracic And Mediastinal Disorders

Cough, Dyspnea, Respiratory failure, Oropharyngeal pain, Oropharyngeal discomfort, Laryngeal edema, Productive cough, Dysphonia, Rhinorrhea, Phlegm retention

◆Ear And Labyrinth Disorders

Tinnitus

◆Heart Disorders

High output heart failure, Tachycardia

◆Nervous System Disorders

Somnolence, Lack of sleep, Headache, Cerebral infarction, Floating vertigo

◆Renal and Urinary Disorders

Hematuria

◆Metabolic And Nutritional Disorders

Loss of appetite, dehydration

◆Skin And Subcutaneous Tissue Disorders

Acne, Pruritus, Rash, Skin pain, Urticaria

◆Lab Test

Increased blood pressure, Decreased heart rate

NOTE:

4) "Aspiration pneumonia" in an 88-year-old male. Underlying conditions: Hypertension, Dementia.
20 days after the administration of the drug, pneumonia symptoms were observed in a resident of the facility. On the 21st day after the drug administration, the pneumonia symptoms worsened, leading to transfer to another hospital. Subsequently, the patient passed away (date of death unknown).

7) "Urinary tract infection," "dehydration" in a 70-year-old male.
25 days after the administration of the drug, symptoms such as hematuria, fatigue, and decreased appetite were observed. On the 26th day after the drug administration, he was unable to eat, and due to dehydration and urinary tract infection, he was transferred to another hospital from the facility. He later passed away (date of death unknown).
Reporting physician: Since this was a case from the facility, the cause of the urinary tract infection is unknown, and it cannot be definitively stated whether it was due to KOSTAIVE®.

8) "Death" of a 71-year-old female. Underlying conditions: None. Medical History: Chronic heart failure, Aortic valve insufficiency, Hypertension. Allergy history: Urticaria.
Died 21 days after vaccination. Information regarding the cause of death and the circumstances leading to death is unknown.
Reporting physician: Although I could not ascertain the cause of death or the circumstances leading to it, I had informed the vaccinated individual to contact me if anything occurred after the vaccination. However, there were no reports of adverse reactions. When I received a call from the family of the vaccinated individual, they only expressed gratitude for the treatment received during regular check-ups and mentioned the death. Therefore, I believe there is no causal relationship with the vaccination.

In an interview, the president of Arcturus Therapeutics stated the following about concerns about the company's amplicon vaccine, KOSTAIVE®:

We would like to collect data for many years and publish the long-term effectiveness and safety in literature.

Unknown side effects have been reported this time as described above, and as he testified, these side effects will be published in papers in the future…

In an interview with the president of Meiji Seika Pharma, his answer was unethical and disturbing.

Question:

Isn’t it also necessary to have empathetic communication with people who feel anxious?

Answer:

No, it’s important to clearly convey that you should get vaccinated. If we say, “Whether or not to get vaccinated is up to the individual,” no one will take the risk and get vaccinated. We should say, “You should get vaccinated, but there is a certain percentage of severe side effects,” and then have people think it over for themselves.

At this point, it seems that he did not anticipate the existence of unknown side effects at all. Many unknown side effects have been confirmed in just 4 months herein Japan. They conducted clinical trials in Vietnam on more than 16,000 people, but everyone would suspect that there was an error in the method of counting side effects in the trials.

Of course, in Japan, the situation is different because the main target of vaccination is the elderly over 65 years old, and many have received 5-7 or more doses of conventional mRNA vaccines.

However, KOSTAIVE® is in a policy framework where that situation is assumed, and therefore their outlook can only be described as extremely optimistic. And the regulatory authorities approved this can only be described as foolish.