pac*****

ヒワマンさん退任ですね。
https://investors.medicinova.com/node/12786/html

DCMのトライアルのデザインが気になる方はどうぞ。
少し読んだ感想はRiluzoleが効きそうって言う結果が出てるんですね〜。

https://bmjopen.bmj.com/content/bmjopen/13/3/e061294.full.pdf

Abstract

Background:
In the SPRINT-MS clinical trial, relative to placebo, ibudilast treatment was associated with significant reductions in rates of whole brain, brain substructure, and retinal atrophy in people with progressive multiple sclerosis (PMS). This effect was more pronounced in people with primary PMS (PPMS) than secondary PMS (SPMS). Whether ibudilast treatment modulates quality-of-life measures and the utility of baseline serum neurofilament light chain (sNfL) levels for predicting changes in these scores in PMS, and the differences therein between PPMS and SPMS remain unclear.
Objectives: To determine whether ibudilast treatment improves quality-of-life scores in people with PMS in the SPRINT-MS clinical trial and whether this effect differs between PPMS and SPMS. Moreover, we sought to assess the relationships between baseline sNfL levels and changes in physical and mental health quality-of-life scores in this PMS cohort.

Methods:
SPRINT‐MS was a randomized, placebo‐controlled 96‐week phase 2 trial that enrolled 134 people with PPMS and 121 with SPMS (129 randomized to ibudilast and 126 to placebo). The short form 36 health survey (SF-36) was used to derive the standardized physical composite summary (PCS) and mental composite summary (MCS) scores. Levels of sNfL were measured annually using single-molecule array immunoassay and were categorized as low (≤25.5 pg/mL) or high (>25.5 pg/mL). We examined the effect of ibudilast treatment and the relationship of baseline sNfL levels with PCS and MCS scores using linear mixed-effects regression models.

Results:
The rate of change in PCS was -5.5% per year in the ibudilast arm and -5.3% per year in the placebo arm (difference: -0.2%; 95% confidence interval (CI), -18.9% to 18.5%, p=0.6) and in MCS was 1.8% per year in the ibudilast cohort and -2.4% per year in the placebo arm (difference: 4.3%; 95% CI, -5.3% to 13.9%, p=0.4) over 96 weeks. Subgroup analyses did not show differential treatment effects of ibudilast relative to placebo on these quality-of-life scores in PPMS (for PCS, p=0.6; for MCS, p=0.2) or SPMS (for PCS, p=0.7; for MCS, p=0.6). Relative to those with lower baseline sNfL levels, people with higher baseline sNfL levels exhibited significantly greater decline in MCS scores (difference: -18.3%, 95% CI, -33% to -3.7% p=0.014) over the study period. This effect was primarily driven by the PPMS cohort (difference: -19.7%, 95% CI, -39.7% to 0.3%, p=0.054).

Conclusions:
Baseline sNfL levels may predict a decline in MCS scores in people with PMS, more prominently in the PPMS subtype. Although ibudilast treatment has been shown to reduce whole and substructural brain and retinal atrophy in people with PMS, it does not appear to improve SF-36 PCS or MCS quality-of-life scores. Ibudilast similarly did not reduce disability progression in this cohort. Thus, in PMS, measurable brain and retinal atrophy benefits may not necessarily translate into measurable clinical benefits.

>>No. 20580

ACTRIMSの解析結果は、IRで見解示してもらいたいとこですが、私の見解を。

記事しか見れていないので私の推測ですが、結論から言うと影響なしと考えております。
以前よりEDSSの結果は公表されてますが、有意差はありませんでした。ですので、今回の結果でQOLに有意義がない結果には、驚きはありません。
但し、以前よりSPMSの寛解なしで46%のリスクを低減出来ることが分かっていますので、phase3には寛解なしの患者で望む予定です。今回の学会も寛解なしでどの程度差が出ているか見れたら結論が変わったかもしれません。まあ、Ｎ数が少ないので有意差が出るかは微妙ですか。

あくまで私の推測ですのでご参考程度に

>>No. 20551

ありがとうございます。
２月２４日に延長契約結んでますね。

日本とアメリカで一貫性のない資料は、辞めて欲しい。IRのプロを雇って伝えるべき事が分かる資料にしてほしい

コーポレートプレゼンテーションがアップデートされてますね。
何が更新されたんですかね？

https://medicinova.com/wp-content/uploads/2023/02/Medicinova-Corporate_2-22-2023.pdf

決算短信出ましたね。

冒頭見て、気になったのは２点。
①決算発表の説明会の開催が有り
最近行ってなかったが、今回は開催するのかな？

②以下の文章の提携のくだり。以前から記載あった？

以下、決算短信から引用
また、本資料の発表日現在においては、次期（2023年12月期）の事業費用について、営業費用として21.2百
万米ドル（約2,765百万円）（前期比＋45.2%）の支出を見込んでおりますが、提携契約の締結に至った場合、
契約の内容によっては研究開発費の一部が相手方負担となる可能性もあり、連結業績の合理的な予測が困難な
状況であるため、現時点においては今期の業績予想を記載しておりません。

ストックオプション
去年の業績達成度は95%で一昨年より大幅アップしているので、今年は何かしらの進捗が期待できそうですね。

>>No. 22195

以前紹介した発表の内容が記事になってますね。
結果は良好とのこと。

Ibudilast has a significant beneficial effect on slowly evolving lesions (SELs) in patients with progressive multiple sclerosis (MS), new data suggest.

Through its effect on SELs, "we have a suspicion that ibudilast may be exerting some of its protective effect by abrogating chronic active lesions," study investigator Daniel Ontaneda, MD, Mellen Center for Multiple Sclerosis at Cleveland Clinic, in Ohio, told Medscape Medical News.

The findings were presented at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) 2022.

First-in-Class Agent
Chronic active lesions (CALs) contribute to clinical worsening among patients with MS. SELs have been proposed as a biomarker for CALs and have been associated with worsening disability.

Ibudilast is an investigational, first-in-class, orally bioavailable small-molecule phosphodiesterase-4 and -10 inhibitor and macrophage migration inhibitory factor inhibitor.

As previously reported by Medscape Medical News, the drug has shown promise as a treatment for progressive MS in the phase 2 multicenter SPRINT-MS trial.

In the new analysis, Ontaneda and colleagues assessed the effect of ibudilast on SELs on MRI scans using data from 195 SPRINT-MS participants with primary or secondary progressive MS. Ninety-seven patients received oral ibudilast (up to 100 mg/d), and 98 received matching placebo.

At baseline, the mean SEL volumes were 1.08 mL in the ibudilast group and 1.49 mL in the placebo group.

Overall, treatment with ibudilast was associated with a significant 26% decrease in SEL volume (P = .004). There was some evidence that the impact was greater for patients with primary progressive MS.

Collectively, the data continue to suggest a beneficial effect of ibudilast in MS, the researchers report.

"Tantalizing" New Data
Reached for comment, Shiv Saidha, MBBCh, MD, professor of neurology, Division of Neuroimmunology and Neurological Infections, Johns Hopkins Hospital and Johns Hopkins University School of Medicine, Baltimore, Maryland, said ibudilast is a "promising therapy with a novel mechanism of action thought to reduce activation of microglia.

"It's hypothesized that the enlargement of these slowly evolving lesions, which correlate with disability accumulation, might be related to ongoing microglial inflammation and this drug might reduce that, which is tantalizing," Saidha, who was not involved in the study, told Medscape Medical News.

Saidha said it's also "fascinating" that ibudilast seems to consistently have a greater impact in primary progressive MS than secondary progressive MS.

"It raises all sorts of questions about the pathobiological underpinnings of these two subtypes of the disease that many of us conventionally think of as being very similar to one another pathobiologically.

"But maybe either they're pathobiologically not as similar as we think, or in order for the for these drugs to be beneficial in secondary progressive MS, they need to be given much earlier," Saidha commented.

今年のECTRIMSでSPRINT-MS studyの内容が発表されます。メディシノバ共著にはなっていないですが。

参考

P188 Effect of ibudilast on slowly-evolving lesions in progressive multiple sclerosis
Kunio Nakamura (United States)
K. Nakamura1, J. Bena2, R. Fox3, D. Ontaneda3
1Cleveland Clinic, Biomedi, Cleveland, United States, 2Cleveland Clinic, Quantitative Health Sciences, Cleveland, United States, 3Cleveland Clinic, Mellen Center for Multiple Sclerosis, Cleveland, United States

Background: Chronic active lesions (CALs) are considered a contributing mechanism of clinical worsening in multiple sclerosis (MS). Slowly-evolving lesions (SELs) have been proposed as an in vivo biomarker for CALs and have been associated with disability worsening. Ibudilast was investigated in progressive MS in a phase II multi-center clinical trial (SPRINT-MS), and ibudilast’s inhibition of phosphodiesterase suggested a potential effect on CALs.
Objective: To evaluate the effect of ibudilast on SELs.
Methods: SPRINT-MS involved brain MRIs every 24 weeks for 96 weeks. Inclusion criteria were either primary or secondary progressive MS according to 2010 criteria and EDSS 3.0-6.5. For this analysis, at least 4 MRIs without scanner change from baseline MRI were required. The analysis involved nonlinear registration of all follow-up MRIs to subject’s baseline MRI to obtain maps of Jacobian determinant. For SEL detection, we performed voxelwise linear regression over time within the baseline T2 lesions. The cutoff between 7.5 and 20%/year was used to determine the SELs. Finally we measured the volumes of voxels meeting these cutoffs. We determined the effect of ibudilast on SEL volume using linear regression with covariate adjustment of baseline T2 lesion volumes (T2LV). We further evaluated the treatment effect in subtypes (PPMS vs SPMS) by interaction term as well as stratified models. Disability progression was evaluated using Cox proportional hazard and log-rank tests with dichotomized and quartiles of SEL volume. R software with survival package was used.
Results: Of 255 randomized patients in the core study, 33 dropped out, 1 had only 3 scans, and 26 had a change in scanner. The remaining 195 patients were analyzed. The mean SEL volumes were 1.08 ml (SD=1.32) in ibudilast and 1.49 (2.00) in placebo. After the baseline T2LV adjustment, ibudilast was associated with a 26% decrease in SEL volume (p=0.004). The interaction between treatment and MS subtype was not significant (p=0.58), and stratified models showed similar treatment effects of in PPMS (30%) and SPMS (21%). There was no significant difference between SEL categories for disability progression in any of the time to event analyses.
Conclusion: We observed a significant treatment effect of ibudilast on SEL. This was consistent with proposed mechanism of action (microglia inflamed in MS) and adds to the efficacy profile of ibudilast in progressive MS

資金調達？？

最大2億ドル
https://investors.medicinova.com/node/12636/html

退役軍人関連の治験はこれですね。
以下のリンクには退役軍人などの記載はないですが。

https://clinicaltrials.gov/ct2/show/NCT03341078?term=ibudilast&draw=2&rank=2

下記リンクのグーグル翻訳

私たちは画期的な法律を実行に移す準備ができている、と全米アカデミーの会長は言う
ステートメント| 2022 年 8 月 17 日
科学、工学、医学が、最近議会を通過し、バイデン大統領によって署名された歴史的な法律の中核であることを嬉しく思います。この画期的な法律は、米国の競争力と国家安全保障を強化し、米国のインフラを強化し、イノベーションを推進する基礎研究を促進し、経済の脱炭素化と地球と人間の健康の保護において真の進歩を遂げるでしょう。さらに、この法律は、何百万人ものアメリカ人の処方薬のコストを下げるのに役立ち、海外勤務中に毒素への曝露の長期的な影響に苦しんでいる退役軍人に注意を払う.

何十年もの間、全米アカデミーの活動は、米国経済の強化、気候変動との闘い、医薬品をより手頃な価格にすること、退役軍人の健康と福利を改善することなど、求められている多くの行動の基礎を築くのに役立ってきました。.

国がこれらの法律を実行に移すにつれて、全米アカデミーは、より広範な科学、工学、医療および健康のコミュニティを動員して、解決策を知らせ、実施するのを支援する準備ができています。特に、新しい法律の 1 つによって求められているように、新しい技術総局について全米科学財団にアドバイスを提供できることを楽しみにしています。私たちは、科学、工学、および医学に対する国家の継続的な投資に感謝しており、それらが社会全体に利益をもたらすことを保証することに引き続き専念しています.

マーシャ・マクナット
米国国立科学アカデミー会長

ジョン L. アンダーソン
米国国立工学アカデミー会長

ビクター・J・ザウ
米国国立医学アカデミー会長

メディシノバUSが呟いた内容は、何だろう。
退役軍人のための薬にイブジラストを使うのかな？？

We Stand Ready to Put Landmark Legislation into Action, Say National Academies’ Presidents https://www.nationalacademies.org/news/2022/08/we-stand-ready-to-put-landmark-legislation-into-action-say-national-academies-presidents?utm_source=NASEM+News+and+Publications&utm_campaign=4f373bfa21-EMAIL_CAMPAIGN_2022_08_19_02_40&utm_medium=email&utm_term=0_96101de015-4f373bfa21-107042729&mc_cid=4f373bfa21&mc_eid=734d107334 via @theNASEM

>>No. 18458

ずっと進捗なしですね〜
https://register.epo.org/application?number=EP19794366&tab=main

新たな治験が予定されてるのは、資金調達したグリオブラストーマかな！？

社長メッセージ&補足資料出ましたね。
多発性硬化症についてはコメントなし。
導出はなくなったのかな。。

見にくいのは許してねw