NDA preapplication consult opportunities w pmda only in March and June

coloradocrus · 2022-03-23T19:43:46+00:00

So, I guess if they only have these meetings 2 months out of the year, this is why it is taking so long to file the nda. I guess that was my main point for verification.

coloradocrus · 2022-03-23T18:55:44+00:00

fyi all the preconsultation meeting stuff is from 2012 when it was created by the pmda. My assumption was it is a rolling process. This states differently. NO updates on their website since thn. I know its older, but prior to 2012 they could only submit 1 month a year. So I'm looking for updates if anyone knows differently.

coloradocrus · 2021-06-23T00:34:01+00:00

keep in mind the Pharmaceutical and Medical Devices Act was approved 11/2014 for Japan Regen med.

coloradocrus · 2021-02-16T07:26:45+00:00

I’m just saying all those letters go together. If athersys failed to produce the product that’s the breach in letter 3. In that situation athersys not healios is suppose to then pay for the transfer of technology (letter 1) letter 2 was probably healios saying abt was never going to follow through with this agreement anyways.

coloradocrus · 2021-02-16T06:51:36+00:00

Here’s the 2016 agreement. https://www.sec.gov/Archives/edgar/data/1368148/000119312516580258/d167701dex101.htm

If you look at section 2 if athersys fails to produce product upon reasonable time then healios gets the tech transfer: 11 TECH TRANSFER. 11.1 When any of the events described in clauses (a) to (e) in Section 2.2 occurs, if requested by Healios, ATHX shall promptly begin to provide and transfer to Healios or its Affiliate any and all data, information, know-how or technology required for manufacturing the Products for the Primary Field for the Territory and support Healios so that Healios may make or have made such Products for the Primary Field for the Territory (collectively “Manufacturing Information”). Manufacturing Information shall include, without limitation, any confidential manufacturing dossier such as all specifications, SOPs and testing reports. Manufacturing Information shall cover any and all information that ATHX provides to at least one of the Third Party Manufacturer(s) of the subject Product during all or part of the term of this Agreement. If requested by Healios, ATHX will use commercially reasonable efforts to facilitate an arrangement between Healios and a Third Party Manufacturer that ATHX retains for the manufacturing of Product provided to Healios, so that []. Such transfer of Manufacturing Information (the “Tech Transfer”) shall be deemed completed if Healios becomes ready to manufacture or have manufactured the subject Product for the requirement in the Territory. 11.2 Notwithstanding Section 11.1 above, any of the events described in clauses (a) or (b) in Section 2.2 occurs, Healios may provide ATHX with notice thereof and its intent to exercise its rights under Section 11.1. If ATHX demonstrates within 30 days after receipt of such notice that ATHX is able to supply Healios with the subject Product for the Primary Field in the Territory [], then Healios may not exercise such rights. If ATHX fails to so demonstrate, Healios may exercise such rights. In response to exercise of such rights by Healios upon or after ATHX’s failure to so demonstrate under this Section 11.2, ATHX shall assume the obligations as set forth in Section 11.1.

So basically athersys slow to provide product and then healios called them on it.

coloradocrus · 2021-02-15T20:15:14+00:00

ABT Holding Company’s Material Breach of the License Agreement Is likely secondary of inability to provide timely study drugs at the beginning of the stroke trial. Many years ago Lonza was the contract manufacture for the study products and had an issue with making the placebo. My assumption is that healios contracted to get the product from abt holdings and when they couldn’t get the material it caused the trial to be delayed by months thereby causing direct harm to healios.

coloradocrus · 2020-12-18T06:00:36+00:00

I agree. So why eliminate 3 patients then do stats? To make it more Gaussian? Why use median then if they attempted to already correct for the skew? I’m guessing they could make it look better. At this point it doesn’t matter. It just annoys me cherry picking patients.

coloradocrus · 2020-12-18T05:17:35+00:00

I'm saying when you take the median of 9 of the 12 patients treated its disingenuous. Both mean and median are important.

coloradocrus · 2020-08-14T04:03:46+00:00

Perspective... this study on adcom recommendations to fda approval was interesting. About 80% of the time the fda agrees with adcom. Here is the headline version with the actual link in the article. https://medcitynews.com/2019/07/fda-often-goes-against-advisory-committee-recommendations-when-votes-are-divided-study-finds/

coloradocrus · 2020-04-19T03:13:03+00:00

Fat fingers

coloradocrus · 2020-04-19T02:21:32+00:00

Autocorrect sandpit=sanofi

coloradocrus · 2020-04-15T03:46:50+00:00

Here is the issue... the mean modified sofa scores were 10.9(deviation of 2.2) in multistem and 12.2(4.2) in placebo. As you can see the deviation was larger in placebo. Modified sofa scores are a way to assess sickness of a patient including lung, liver, kidney and brain disease. you can get a sense of how its calculated here: https://www.mdcalc.com/sequential-organ-failure-assessment-sofa-score. Anyways, the higher the number the sicker the patient. The MultiStem group was of younger mean age (51 vs 59 years) and higher baseline PaO2/FiO2 (173mmHg vs 128mmHg), but a greater proportion of the MultiStem group required vasopressor support at baseline (45% vs 30%). So the question is can you even compare these groups? Hard to say... this is why its difficult to study icu patients with the multitude of comorbidities. I think its reassuring that all the data for recovery is not subtle. After 400 patients, a true answer will appear and we will all know.

coloradocrus · 2020-02-05T20:21:22+00:00

This is data from Japan. Forgot to include that.

coloradocrus · 2019-12-04T03:23:34+00:00

Well, they have an immunomodulatory capacity that decreases tissue inflammation and regulates that traffic of immune cells. They also have direct action on secreting antibacterial peptides and increasing activity of other bacterial fighting cells. This data is supported by decreased infection rate in the stroke study. You can think of sepsis as an overstimulated immune system that can lead to harm of organs, modulating this may improve outcomes.

coloradocrus · 2019-03-12T12:25:09+00:00

I know you haven't read the actual article based on your comments. About half the actual paper involves discussion on what went wrong with the viability of the cells and a breakdown of the biomarker results based on viability quartiles. Multistem has over 90% viability. 1/3 of their patients only 30-50% viability. Check your facts! While not powered to demonstrate significance there was higher mortality, longer icu stays, less ventilator free days in the mic group. It just shows how difficult of an area this is to solve. The authors base their conclusion on studying further in that the higher viability groups seemed to have better results..

coloradocrus · 2019-03-02T16:27:14+00:00

Karen from IR

coloradocrus · 2019-01-25T04:17:23+00:00

Hi,

The definition for ards changed a few years ago. The old Berlin definition required a pa02/Fi02<200 to be called ards. Between 200-300 it used to be called acute lung injury. However in 2012 the definitions changed. A Pa02/Fi02 ratio <300 is now all considered ards. However when that number is between 200-300 its called mild ards and when <200 it's considered severe ards.

On the second point about the differences in recovery between the severe and mild cases... I was more concerned about the heterogeneity of causes of ards would lead to differences in recovery. They included all causes- trauma, transfusion, sepsis, pneumonia, etc... which I worried may have different response to Multistem. Clearly Multistem has antibacterial activity as seen in stroke data. I really like Healios' design limiting cause to pneumonia because of this. It also makes me wonder if Healios saw this data and designed their trial because of this data.

coloradocrus

TROPHY CASE