Taiyo : Notice regarding acquisition of approval to add indications, etc. for “Kytril injections and intravenous infusion bags” that act as 5-HT3 ...

ENGLISH TRANSLATION OF JAPANESE-LANGUAGE DOCUMENT

This is a translation of the original Japanese-language document and is provided for convenience only.

In the event of any discrepancy between this translated document and Japanese original, the original shall prevail.

February 25, 2022

To whom it may concern:

Company Name:	TAIYO HOLDINGS CO., LTD.
Representative:	Eiji Sato, President and CEO
	(Code: 4626, Listed on First Section of
	Tokyo Stock Exchange)
Inquiries:	Sayaka Tomioka, Executive Officer,
	General Manager of Corporate Planning
	Department
	Tel: [phone] (main line)

Notice regarding acquisition of approval to add indications, etc. for

"Kytril® injections and intravenous infusion bags"

that act as 5-HT3 receptor antagonists

TAIYO HOLDINGS CO., LTD. (hereinafter, "TAIYO HOLDINGS") hereby announces that today, its consolidated subsidiary TAIYO Pharma Co., Ltd. (hereinafter, "TAIYO Pharma") obtained approval from the Ministry of Health, Labour and Welfare to add indications, dosages and administrations pertaining to "postoperative gastrointestinal symptoms (nausea, vomiting)" for "Kytril® injection 1mg," "Kytril® injection 3mg," "Kytril® intravenous infusion bag 3mg/50mL" and "Kytril® intravenous infusion bag 3mg/100mL" (generic name: granisetron hydrochloride) (hereinafter, collectively "Kytril® injections and intravenous infusion bags"), which act as 5-HT3 receptor antagonists.

1. Circumstances leading to acquisition of approval

After a request for the development of "Kytril® injection and intravenous infusion bag" was issued by the Japanese Society of Anesthesiologists, at the meeting of the "Committee on Unapproved or Off-labeled Drugs with High Medical Needs" that convened on July 12, 2021, 1) "Kytril® injection and intravenous infusion bag" are publicly known in medical and pharmacological sciences for "postoperative gastrointestinal symptoms (nausea, vomiting)." Furthermore, at the meeting of the First Committee on Drugs under the Pharmaceutical Affairs Council that convened on August 30, 2021, it was concluded that there would be no issue with filing a public knowledge-based application2) for that purpose. Based on the above, on September 22, 2021, TAIYO Pharma filed a public knowledge-based application to add indications, dosages and administrations, which resulted in it obtaining the approval in question.

In addition to causing patients distress, Postoperative Nausea and Vomiting (hereinafter, "PONV") is also a factor that delays their postoperative recovery. Indications pertaining to PONV in adults have been approved for granisetron hydrochloride injections in Europe, the United States and other countries and regions. In textbooks and clinical guidelines within and outside of Japan, the drugs have been positioned as a standard therapeutic agent in the prevention and treatment of PONV in adults.

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ENGLISH TRANSLATION OF JAPANESE-LANGUAGE DOCUMENT

This is a translation of the original Japanese-language document and is provided for convenience only.

In the event of any discrepancy between this translated document and Japanese original, the original shall prevail.

Going forward, in addition to its endeavors to facilitate contributions by "Kytril® injection and intravenous infusion bag" as new therapeutic agents for "postoperative gastrointestinal symptoms (nausea, vomiting)," TAIYO Pharma will continue to do its part for the provision of pharmaceutical products that address feedback from the medical frontlines.

1. The Committee on Unapproved or Off-Labeled Drugs with High Medical Needs was established with the aim of contributing to the promotion of the development of unapproved drugs and off-labeleddrugs by pharmaceutical companies by assessing the medical need for drugs and indications that are approved for use in Europe and the United States but not approved in Japan, and by evaluating the relevance of these drugs for public knowledge-basedapplication and confirming the appropriateness of the tests that need to be performed additionally for application for approval.
2. Public knowledge-based application refers to an application for approval made without conducting all or part of clinical trials on the basis that the drug has already been approved for relevant indications in a foreign country and the efficacy and safety of the drug are medically known.

2. Product overview

Brand name		Kytril® injection 1mg
		Kytril® injection 3mg
		Kytril® intravenous infusion bag 3mg/50mL
		Kytril® intravenous infusion bag 3mg/100mL
Generic name	Granisetron hydrochloride
Indications		Gastrointestinal symptoms (nausea, vomiting) associated with the
		administration of antineoplastic agents (cisplatin, etc.) and irradiation
		Postoperative gastrointestinal symptoms (nausea, vomiting)
Dosages	and	Gastrointestinal symptoms (nausea, vomiting) associated with the
administrations	administration of antineoplastic agents (cisplatin, etc.)
		Adults: Typically, adults are administered one 40μg/kg dose per day as a
		granisetron via intravenous injection or drip. Note that the dose is increased
		or decreased as appropriate depending on the patient's age and symptoms.
		In cases where symptoms do not improve, a single additional 40μg/kg dose
		may be administered.
		Children: Typically, children are administered one 40μg/kg dose per day as a
		granisetron via intravenous drip. Note that the dose is increased or decreased
		as appropriate depending on the patient's age and symptoms. In cases where
		symptoms do not improve, a single additional 40μg/kg dose may be
		administered.
		Gastrointestinal symptoms (nausea, vomiting) associated with
		irradiation
		Typically, adults are administered a single 40μg/kg dose as a granisetron via
		intravenous drip. Note that the dose is increased or decreased as appropriate
		depending on the patient's age and symptoms. However, the maximum
		number of doses per day is two.
		Postoperative gastrointestinal symptoms (nausea, vomiting)
		Typically, adults are administered a single 1mg dose as a granisetron via
		intravenous injection or drip. Note that the dose is increased or decreased
		as appropriate depending on the patient's age and symptoms. However,
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ENGLISH TRANSLATION OF JAPANESE-LANGUAGE DOCUMENT

This is a translation of the original Japanese-language document and is provided for convenience only.

In the event of any discrepancy between this translated document and Japanese original, the original shall prevail.

		the maximum dose per day is 3mg.
Precautions		(Universal for pharmaceutical formulation)
regarding		When using for gastrointestinal symptoms associated with irradiation,
dosages	and	administer via intravenous drip prior to irradiation. Note that when using for
administrations	gastrointestinal symptoms associated with Total Body Irradiation (TBI) upon
		pretreatment for hematopoietic stem cell transplantation, the administration
		period should ideally be four days.
		When using for postoperative gastrointestinal symptoms, administer with
		appropriate timing before and after operation after taking the patient's
		background, the operative method, etc. into consideration.

*The underlined areas have been added.

3. Future outlook

The impact of this matter, including that on the consolidated business results of TAIYO HOLDINGS for the fiscal year ending March 31, 2022, will be minute. However, TAIYO HOLDINGS will promptly provide notification of any matters that merit disclosure should they arise.

End

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