Quite Surprising that....

[Hoosier Investor]

The ADCOM chairperson (Ravi) would vote "No" to the Benefit/Risk question.

How could a practicing physician knowingly withhold a treatment that is going to benefit 40% of their sick patients? In this case, we're talking about a treatment that is going to allow a significant portion of your patients to resume their normal life for a period of 1-4 years? A much better (obvious) approach would seem to involve informing the patient of the potential risks and letting them make their own treatment decision(s).

Ravi did a good job of facilitating the meeting, and I'm glad he didn't try to bias/influence the vote. However, I'm struggling with the rationale behind his "no" vote.

[Ryan]

He did state his rationale - that the risks ultimately outweighed the benefit. He bought into the FDA shaping of the cytopenias, despite multiple clinicians (and he would also know) that these are manageable in MDS centers.

I think a real interesting moment was when the Dr from the Moffitt Center in FL, a real brass tacks guy, stated his interest in understanding why the Lancet was so different that the FDA data sets … and Geron Doc stepped up and basically said, as lead author of the Lancet paper, the data was prepared how scientists do it.

Another doctor, not a heme doc, stated she has been on multiple ODACs and never has FDA and Applicant ever been at such polar opposites.

The Chair of the ODAC voting no does get me a little nervous for June, to be honest.

[biopearl123]

Who was the second no vote?

[rccola335]

Believe it was the guy from university if Virginia

[LWS]

These were the no votes (12 yes, 2 no)

2. AC-Ravi Madan(Chair) NO
8. AC-Mark Conaway NO

As I remember some of the no reasons were:

1. Only a subset of people benefitted
2. Unnecessary disease in those that did not benefit
3. No biomarkers
4. Quality of life (feeling better) is too subjective to be considered

However, all agreed that transfusion independence was an important goal.

It was surprising that the Chair voted no.

[ashah]

The second no was from a Statistician. Interesting - since the primary and secondary end points were met. Yet the stats expert voted No.
A conundrum. If the recommendation is a NO after previously agreed upon endpoints are met ‐ how will the pharma industry ever develop drug? What is the point of agreement with FDA on the endpoints? And what does statistical significance even mean?
No wonder the latest study shows cost of drug to be over $2 Billion!

[biopearl123]

Great point, the FDA sets a statistical bar, it is met, but once it is, it’s still not enough? Thank G-d statisticians don’t treat patients. I am still stuck on the brew ha ha over the absence of CR’s and PR’s. Maybe someone can help me here. If LR patients have < 5% blasts, how does one assess a PR or CR? I suspect that’s just a shoe that doesn’t fit. What does fit and is a much better way to assess response is the decrement in transfusion burden and the rise in hemoglobin. That’s how you tell the drug is working. You could also look for markers that correlate to a reduction in the malignant clone which they did! Studies are hard and its difficult to control all of the variables, that’s were stats and P values help, there was one patient if I am correct in the placebo group that refused transfusions despite having very severe anemia. I think this person (speculation) thought they were helping the study by staying on “drug” knowing a transfusion would end the “transfusion free interval”. Can’t control for that!

[Bigfun]

Yea talk about throwing the baby out with the bath water with those no votes, especially after hearing first hand from patients and doctors who are specialists on the frontlines of this thing. The chair seemed very casual and chipper with his vote, not sure the other really justified his "no" very well and just seemed a bit grumpy.

In any case does anyone recall if there was any work being done to figure out why certain people respond really well and others do not? I could have sworn there was some research into this but maybe I conflated that with the MF study. It seems that if we could more selectively figure out which patients would almost certainly benefit then I believe the risk would always be worth it.

[LWS]

Bigfun --- The researchers have been looking for biomarkers to separate those patients that can benefit from Imetelstat from those that cannot. So far, none have been found.

I believe that is one of the reasons why the Chair voted no. Most (12) believed that it was important to have this medicine in their 'toolkit' for a variety of reasons beyond transfusion independence, including better quality of life and increased overall survival time.

[Bigfun]

Thanks LWS, yea that was my understanding as well. I just thought maybe there were some clues as to why some do better that maybe did not come to the forefront of the ADCOM meeting but that had maybe been discussed. I would think that having more information here would be a good marketing tool and at the same time really help doctors make good decisions with treatment options. Probably a good problem for an AI system to crunch on.

[biopearl123]

You can be sure that research will be directed here, especially with EHA and ASH coming. The problem of course is that if subgroups are identified, the market could narrow. More likely will be a search for an effective combination.