english： FSHD ニュースレター VOL1

1.Trends in drug development

The World FSHD Alliance Meetng last year (October 2022) was very exciting.

Most notably, Rosmapimod, which is undergoing international clinical trials, is showing very encouraging data in a Phase 3 clinical trial.

Phase 3 clinical trials have shown its efficacy in slowing or stopping disease progression in patients who have been on the drug for up to two years, according to the drug company that developed it, Fulcrum Therapeutics.

The sustained ability to slow or halt the progression of FSHD over two years underscores the significance of our Phase 3 REACH trial and the potential of losmapimod to be the first approved treatment for FSHD.

Apart from Losmapimod, multiple pharmaceutical companies have been developing as shown in the table below. (List only those that have entered Phase 2 clinical trials)

治療薬名　　　　（開発コード）	Pharmaceutical company	進捗状況	治療手段
Losmapimod	Fulcrum Therapeutics	Phase 3	p38α/β MAPK 阻害薬
AOC 1020	Avidity Biosciences	Phase 2	核酸医薬
GYM329	ロシュ（スイス）	Phase 2	​マイオ スタチン阻害薬

Then, assuming that Losmapimod clears the Phase 3 clinical trial and is approved by the FDA, the regulatory authority in the United States, what will happen to insurance coverage of therapeutic drugs in Japan?

First of all, the pharmaceutical company Fulcrum has a plan to develop and sell Losmapimod in Japan, conduct domestic clinical trials, and have the Ministry of Health, Labor and Welfare (PMDA) approve the drug.

The key point here is, from the perspective of pharmaceutical companies, how many FSHD patients are there in Japan? The estimated number of FSHD patients is 15,000, but it is only an estimate.As of November 2022, 161 patients with genetically confirmed FSHD have been enrolled. From now on, we need to gather the power of patients and strongly promote patient registration.100 is stronger than 1 , 1000 is stronger than 100. numbers are force. It is necessary for us to appeal to domestic and foreign pharmaceutical companies, including Fulcrum, that there are so many FSHD patients in Japan, and that if they develop and sell therapeutic drugs in Japan, they can expect sufficient profitability.

	The estimated number	patients with genetically confirmed	​Remudy開始時期
FSHD	15,000人	161人	2020年９月
DM	10,000人	1170人	2014年10月
DMD/BMD/IMD	確認中	2,104人	2009年7月

2. Remudy patient registration

Are you registered as a Remudy patient?

FSHD Remudy patient registration started in September 2020.Those who can register as Remudy patients must have a confirmed diagnosis through genetic testing.Those who had genetic testing before June 2018 may need additional testing.

One member of the patient group thought his FSHD diagnosis was confirmed because he had a genetic diagnosis when he was 14 years old.The attending physician was also such a recognition.However, at this time, I learned through the Remudy patient registry that the diagnosis has not yet been confirmed.

In the past, FSHD1 was diagnosed based on the result that the DNA in the part called D4Z4 of chromosome 4 is shortened (the number of repeats is 6 times or less).With recent advances in genetic analysis, it was found that even if the DNA is short (the number of repeats is 6 or less), there are rare individuals who are not FSHD1, depending on the results of haplotype analysis.Therefore, in order to confirm the FSHD1 diagnosis, it is necessary to perform an additional detailed examination called haplotype analysis.(Most (more than 90%) of FSHD patients are FSHD1 and the rest are FSHD2.)

The figure below is quoted from NCNP.

When I called the Remudy office, I was told that many doctors (clinicians) still do not know about the additional diagnosis of haplotype analysis.

Therefore, this time, the subcommittee secretariat recommends that a definitive diagnosis be made through the Remudy patient registration. When a patient registration application is submitted, a letter will be sent from the Remudy office to the attending physician regarding the need for additional analysis of the haplotype.

(The haplotype is a specialized part that is difficult for patients to understand, so this system is very helpful.)

The benefits of Remudy patient registration are summarized below.

・The necessity of haplotype analysis can be understood through the Remudy patient registration application.

・In the future, if a clinical trial is started in Japan, you will have an opportunity to be recruited for a clinical trial.(注1)

・it is necessary to update the patient's physical condition data every year,this is why it is possible to know the medical health condition objectively.

・Remudyは、海外患者登録(TREAT-NMD)と連携しているので国際共同治験の参加基盤づくりに繋がります。

補足：今回、ロスマピモドの国際共同治験には、参加できていませんが、今後、登録者数が大幅に増えていけば 国際共同治験の参加の道も開けることも期待できます。 国際共同治験に参加できると、国際同時承認が可能になり、メディカルドラッグラグ(注2)の解消に繋がります。

（注1）治験リクルートは患者自身がリスクありと判断すれば断ることができます。また、　Remudy患者登録をしなくても主治医等を通じて、治験に参加することは可能です。

(注2)　海外で既に承認されている薬が日本国内で承認されるまでに、長い年月を要するという問題。

3.治験、治療薬の勉強会について

当然、治験にはリスクが伴います。今後、患者会で各種治療薬の勉強会を開催することも企画しています。二重盲検試験とは何か？ポジショニングドラッグとは何か？マイオ スタチン阻害薬とは何か？など。基本的なところからみんなで勉強していきましょう。

4.まとめ

以下の通りまとめます。

・ロスマピモドが第 3 相臨床試験において大変有望なデータを示しています。

・患者登録者数を大幅に増やし、国内外の製薬会社に強力にアピールしていく必要があります。

・近年の遺伝学的解析の進歩に伴い、ハプロタイプ解析という詳しい検査を追加で実施する　　　必要があります。

・今後、登録者数が大幅に増えていけば、 国際共同治験に参加、国際同時承認が可能にな　り、メディカルドラッグラグの解消に繋がります

・Remudy患者登録は、患者個人のメリットのみならず、患者全体のメリットに寄与します。

・治験参加にはリスクを伴うので治療薬のメカニズムについて勉強会を今後、企画します。

1年でも早く、1ヶ月でも早く治療を開始する。私たちの想いは同じです。

REMUDYの登録者数の増加、各種治療薬の勉強会、国際治験参加の基盤づくり、国産治療薬の開発支援などにみんなで力を合わせて未来の扉を開きましょう。