In 2017, the drug was approved in the EU.
https://www.ncbi.nlm.nih.gov/pubmed/30814573
https://www.nature.com/articles/s41598-019-39427-4
In vivo, combined ibudilast and TMZ treatment of a patient derived xenograft (PDX) model resulted in significantly longer overall survival. Our findings have significant clinical implications for people with GBM. Since clinical trials involving ibudilast have shown no adverse side effects and the drug readily penetrates the blood brain barrier, treatment of GBM with this combination is clinically achievable.
MIF inhibition in combination with ibudilast and TMZ treatment results in longer survival in vivo. Tumor-bearing mice were treated with indicated drug combinations with the following doses: Ibudilast (5 mg/kg); Ibudilast (20 mg/kg); TMZ (10 mg/kg); Ibudilast (5 mg/kg) + TMZ (10 mg/kg) and Ibudilast (20 mg/kg) + TMZ (10 mg/kg). There were n = 8 mice in all groups. All treatments ceased by day 100.
At 43 days post-implantation, large tumors were present and treatment commenced. When all vehicle-treated mice reached their neurological endpoint (median survival 100.5 days), treatment was stopped. The treatment of tumor-bearing mice with ibudilast only resulted in inferior median survival times compared to the vehicle-treated mice (89 days and 97.5 days respectively) (Fig. 5A). A survival advantage was observed with mice treated with TMZ alone (median survival: 105.5 days compared to 100.5 days; LogRank p = 0.055). Combined treatment resulted in significantly longer survival. Mice treated concurrently with ibudilast (5 mg/kg) and TMZ (10 mg/kg) displayed a median survival of 114 days (p = 0.005) while the combination of ibudilast (20 mg/kg) and TMZ (10 mg/kg) resulted in a median survival of 111.5 days (p = 0.014).
P.S. The authors of the study write about a significant improvement in the survival of mice, but we see that the best survival in the treatment with a combination of drugs is 114 days versus 105.5 days in the treatment with temozolomide alone.
I was about to post on this but you beat me to it!
ReplyDeleteI don't see that the drug has full FDA approval yet.
https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=445814
It's designated as an orphan drug for GBM as of last October, but "orphan drug" status is not the same thing as approval. It still has to go through the clinical trial process before it would be approved for marketing.
https://globenewswire.com/news-release/2018/10/04/1617208/0/en/MediciNova-Announces-FDA-Grants-Orphan-Drug-Designation-to-MN-166-ibudilast-for-Glioblastoma.html
As with human studies the median survival isn't always the most informative metric. In the Ibudilast + TMZ group there were some surviving mice, while in the TMZ alone group there were none surviving. It would have been interesting to do a longer follow up with the surviving mice to see if they were actually "cured" or if the combo just slowed down the tumor growth.
ReplyDeletehttps://clinicaltrials.gov/ct2/show/NCT03782415
ReplyDeleteStudy to Evaluate Ibudilast and TMZ Combo Treatment in Recurrent GBM
This is a phase 1/2 trial, so it's going to be years (if ever) before this could be approved for GBM. The plan for a phase 3 trial in ALS was approved recently, so it would probably get marketing approval in that indication first, and then it could be used off-label, off-trial for GBM, but could be expensive.
The legal situation in Europe looks similar. It got "orphan drug" approval in the EU in 2017, but this isn't the same as marketing approval.
I was also thinking about posting about Ibudilast for some time now.
ReplyDeleteIt's not approved in US but it has been used in Japan and Korea since 1989 to treat post stroke complications and bronchial asthma.
There are some promising results in using Ibudilast to slow progression of brain atrophy in multiple sclerosis: https://www.nejm.org/doi/full/10.1056/NEJMoa1803583 . The article gives an overview of possible adverse effects associated with taking high doses (up to 100 mg per day) over longer period of time.
I recently purchased 2000 Ibudilast 10 mg capsules. I'm awaiting my first chemo cycle to start taking it. I will keep you updated on possible effects.
Here is some data I gathered about Ibudilast. I'm temporarily sharing a link to Ibudilast entry in my personal database until I have time to share it in more suitable format.
ReplyDeletehttps://www.notion.so/mislav/Ibudilast-MN-166-05c155273d5944d3a4ef72aab9a521de
In MediciNova press release they mention "complete tumor regression observed in 2 out of 16 mice".
ReplyDeletehttp://investors.medicinova.com/phoenix.zhtml?c=183833&p=irol-newsArticle&ID=2382746
This is what initially got me interested in Ibudilast but I can't find the actual study with those results.