On the topic of blood transfusions

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biopearl123
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Re: On the topic of blood transfusions

Post by biopearl123 » Thu Sep 09, 2021 5:12 am

Clearly one of the “new indications” will be the short stretch to higher risk MDS. Lower risk MDS+ higher risk MDS = all patients with transfusion dependent MDS

huntingonthebluffs
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Re: On the topic of blood transfusions

Post by huntingonthebluffs » Sat Sep 25, 2021 10:16 pm

Okay, I may not have read this closely enough but if we do some basic math from this study’s conclusions and extrapolate to the 100,000 MDS patients with LR MDS from the HC Wainwright presentation. I think we can say that half of those patients have a transfusion burden of >= 8/16 weeks.

Then 50,000 MDS patients in the USA each require >= 26 transfusions/year for a total of 1,300,000 transfusions in total for the patient set. That equates to over 3,500 transfusions per day. And that doesn’t include those with LR MDS requiring less that 8/16 weeks, anyone with HR MDS, MF, AML, etc., etc.

Why is this not a strong talking point with the FDA? That is very troublesome for me to understand especially given the many risks associated with transfusions and even more complicated for those with cancer.

biopearl123
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Re: On the topic of blood transfusions

Post by biopearl123 » Sun Sep 26, 2021 2:37 am

Hunt slide 17 addresses your numbers question. Note in VERY fine light print that these numbers are projected for 2030. We scream for transparency, well the fine print at the bottom of that slide is so transparent as to be virtually invisible. Good idea about questions for the analysts. Let’s think them up together. Probably the best place to begin is to yet again ask Geron about their IP and if articles such as the one’s you cited would be using same. bp

huntingonthebluffs
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Re: On the topic of blood transfusions

Post by huntingonthebluffs » Mon Sep 27, 2021 11:06 pm

Okay thank you biopearl123, I didn’t do my homework very well and your estimates from the “Reality check” post from April-2020 continues to be in the ballpark. But I’m going to continue to beat the dead hope of sanity here.

If I take from your link above, the 50% of LR MDS patients have a TB of 8/16 weeks. “In summary, this study showed that in a real-life population of MDS patients, almost half of the MDS patients had a transfusion burden of ≥8 RBC units in 16 weeks. This study identified patients >65 years old, high-risk MDS patients, and patients with MDS-MLD or MDS-EB to be at increased risk for developing HTB, but HTB was observed in all MDS subtypes and both low-risk MDS and high-risk MDS patients, demonstrating that the entire MDS population might benefit from novel agents that reduce the need for transfusions. We encourage the development of new therapies that could benefit the entire MDS population.”

So again, if I’m looking at the Geron HC Wainwright presentation metrics correctly, the 100,000 consisted of LR-MDS patients (slide 12) from the US and EU5 while Geron states (slide 17) the key addressable segment is approximately 35,000 by 2030(???) for both USA and EU5, which is likely very, very conservative assuming Imetelstat could apply to 90% of LR-MDS cases and the current number grows for another decade. In addition, the vast majority of those 35,000 patients will probably be in the HTB class needing 8/16 weeks. So given how conservative Geron seems to want to be, another more aggressive (I think more realistic) cut at the math might be nearly 900,000 transfusions per year or almost 2,500 per day. I don’t know what the split between the USA and EU5 would be but if it is a 50/50 split we are looking at 400,000+ annually in the USA and another 400,000+ in the EU5. And as noted before, that doesn’t include those with LR MDS requiring less than 8/16 weeks or anyone with HR MDS, MF, AML, etc., etc.

Getting to the number of actual transfusions that Imetelstat treatment could eliminate is messy at best but however you want to come at it, it will be a very large number. Anyone or entity in the business of managing components of the blood supply should take note. I think if the FDA/EUA were to take this opportunity seriously and calculate the numbers on the low hanging fruit, they would find the numbers to be potentially much higher in both the USA and EU5. And I believe globally the number would likely be multiples of the USA and EU5 requirement.

Secondly, and even more importantly, consider the impact to the “healthcare system” and especially these patients in terms of OS, QoL, cost and time savings, etc. Again, looking at the information in the link you provided above: ““The median OS of HTB patients was almost half of the median OS of LTB or NTD patients and was significantly compromised. HTB was associated with inferior outcomes in MDS, but our data could not demonstrate a causal relationship. HTB is likely a proxy for the severity of the disease.”

I am assuming that if Imetelstat reduces or eliminates the RBC transfusion requirement, the severity of one’s MDS disease would also begin to lessen given the disease modifying MOA.

Lastly, maybe if the people overseeing and / or relying on an efficient/effective blood supply, including the Red Cross would step up and understand these metrics they could add their voices to the KOL chorus in helping the FDA to see what is right in front of their noses and reconsider their alliances, etc.

And BTW, as the science progresses to Imetelstat 2.0 and combinations find their mark, the transfusion savings will only grow even larger. More manipulative use of regulations by the powers to be only pushes this benefit out further as well. One doesn’t have to just care about old sick people as there is value here for everyone, all age groups.

biopearl123
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Re: On the topic of blood transfusions

Post by biopearl123 » Tue Sep 28, 2021 5:12 am

Hunt, love your analysis. The problem I see is that this whole construct fails to account for new and potentially more effective meds over the next eight years.

LWS
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Re: On the topic of blood transfusions

Post by LWS » Tue Sep 28, 2021 10:51 pm

With competition coming, Geron needs to solidify its blood cancer lead with partners and/or a buyout. Geron needs deep pockets to stay ahead (patents, trials, approvals, IMET 2.0, combinations, etc.). I think they know that.

huntingonthebluffs
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Re: On the topic of blood transfusions

Post by huntingonthebluffs » Wed Sep 29, 2021 5:49 pm

I did mention in the "Btw" on my last post that the current math would change as Imetelstat 2.0 and combinations come into the market. I personally don’t see anything to rival the reductions in RBC transfusions, not now, not in 8-10 years, probably just naïve. But I think Imetelstat and Geron stand alone in that space for the foreseeable future. Obviously reducing blood transfusions is a secondary benefit but an important one that isn’t being talked about. Sure science will change and more drugs will find their way into CTs and maybe even commercialization but what are those contenders and where are they in the commercialization process now? I don’t see them and I don’t think 8-10 years to finally arrive is a slam dunk. By then, where would we expect Geron and it’s drugs to be? Certainly much farther down the road in effectiveness and greater transfusion burden reductions. And remember the patents in place today will hold off most if not all competition for many more years in the TI area and especially in regards to hematological cancers.

I don’t disagree that competition is coming rapidly and partnerships can be helpful. But lets not forget the JNJ/Jansen debacle! I’m all for a beneficial partnership but first tell me what that does for Geron vs to Geron. I believe there are a lot of major companies out there that don’t want Geron and Imetelstat to see the light of day. Show me a partnership that truly looks out for Geron and getting it’s science to market versus the partner’s stake and maybe that can be useful otherwise bring Imetelstat to market and do a fair BO if that makes sense. But JS has said Geron’s vision is to become the premier drug company in the hematological cancer arena. So not sure a buy out or any typical partner is going to fit the bill now, but maybe that all changes in November.

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