A Purple Squirrel & Venetoclax Combo - AML & Lymphoid Market Potential

[kmall]

Eighteen months ago, I posted a multi-series post titled “Go Big or Go Home” here on Imetelchat. It covered 2 of the indications Imetelstat was currently targeting in its latest Phase 3 Clinical Trials: IMerge - MDS (Myelodysplastic Syndrome) and IMpact – MF (Myelofibrosis), as well as AML (Acute myeloid leukemia); which for all intents and purposes seemed logical due to approximately 30% of MDS patients’ eventual progression to AML. Each of these indications shared a worldwide connection of underreporting, misdiagnosis, increase of global age population, a decrease in median patient age in certain parts of the world, environmental factors including pollution and finally health issues like smoking and high body mass index, which have all attributed to much higher MDS and MF patient populations than projected - (links to all research and estimates are available here on Imetelchat starting at around pages 10-11 now). In turn, I was able to SPECULATIVELY estimate Potential Annual Global Revenue Stream for these 3 indications. This was the final analysis (posted June 1, 2020):

“In conclusion, from the 3 indications mentioned here we can now project anywhere from a $5.7 - $15.6 Billion or more annual Global market. I would feel comfortable placing this estimate roughly in the middle at around $8 - $10 Billion. As stated earlier, how much of this can be carved out for Imetelstat is still shrouded in mystery, however, if the enthusiasm reflected in last Thursdays CC is any indication – I would stake my claim that it’s quite a fair share.”

Several days before posting “Go Big or Go Home,” on 5/28/2020 Geron held a Conference Call reporting Q1 2020 Financial Results. During that Call, Dr. Scarlett had estimated an Annual Global Market Potential of $1.5 Billion for MDS and $1 Billion for MF, for a combined total of $2.5 Billion. Just two months ago, Geron and Dr. Scarlett increased their estimate for these 2 indications by $500,000,000.00 to $3 Billion – and that was just in the US and 5 largest European Nations…..or a 20% increase. This is quite substantial……. perhaps Dr. Scarlett’s been reading Imetelchat again?

Even though this increase is overly warranted, from my perspective and research, it’s still undervalued. Not to mention, there’s a substantial portion of the world left out of Dr. Scarlett and Geron’s equation….to the tune of about 80%: Europe (44 countries total – 39 countries left out), Asia (China, India, Korea, Japan, Singapore, Taiwan, Vietnam, Thailand…etc.), Africa, Australia and Oceania, South and Central America, West Indies and of course Canada – none of which are considered in Geron’s updated $3B Annual Market Revenue Potential for Imetelstat in MDS and MF.

Since Geron has recently announced AML as an indication for a new “Clinical Program” named IMpress and an additional pre-Clinical program “being conducted at MD Anderson Cancer Center to define the role of Imetelstat in lymphoid malignancies,” I think it’s time to take a more detailed look at these two patient groups and their Global Market Potential.

[kmall]

First let’s review a few of the findings for AML from 18 months ago. These are just as relevant today, and as healthcare tends to, have most likely have increased over time as well:

AML: Market Potential Revisited (from Go Big or Go Home – AML – posted Mon June 1, 2020)………

http://imetelchat.imetelstat.eu/imetelc ... ?f=1&t=977

Global Acute Myeloid Leukemia Market $2.2 Billion by 2025
https://www.ihealthcareanalyst.com/glob ... nt-market/

This 2018 abstract not only goes over financial costs associated with HR-MDS, but also touches on the progression to AML and it’s eventual economic burden. https://link.springer.com/article/10.10 ... 018-0100-5

“In our study, 38.8% of our population progressed to AML, and these patients, along with those who died, incurred higher costs in the first year after diagnosis relative to patients who did not have these events. For non-MDS-related medical costs, inpatient hospitalizations were the main cost driver, accounting for 60% of costs.”

Here is a 2001 abstract from the Netherlands that places the total annual average weighted costs of AML patients amounted to $104,386, keep in mind that’s 20 years ago.
https://pubmed.ncbi.nlm.nih.gov/11276372/

“Treating AML patients is very expensive, and major reductions in costs are not expected in the next future. Considering efficacy and effectiveness, it seemed that choices based on costs could be made between several consolidation techniques and between a specific consolidation technique and/or palliative treatment.”



This (2020 – 2025) AML – Growth, trends and forecast touches on some interesting points -
https://www.mordorintelligence.com/indu ... ics-market

“The rising prevalence of AML in the country (US) is the prime factor responsible for the growth of the market in the country.”

“The American Cancer Society’s estimates for leukemia in the United States, for 2019, indicates that approximately 61,780 new cases of leukemia and 22,840 deaths from leukemia are expected to occur in the country. Among them, the number of new cases of acute myeloid leukemia (AML) will be around 21,450, from which most of the population will be adults. In terms of mortality, the society has estimated that there will be around 10,920 deaths due to AML, in the country. These statistics shows that there is a huge number of people that are prone to suffer from acute myeloid leukemia, which may directly impact the growth of the AML market in the United States.
In addition, the global rise in the incidence of AML, along with increased mortality due to the disease, is expected to create a huge demand for AML therapeutics, thus, augmenting the global AML market.”

There is Map graph included which shows a “High (green)” growth rate for AML in the Asia / Middle East / Australian regions – China & India are also included in these areas.


A 2018 study, published in the AJMC, places the median AML treatment cost per patient / “episode” at anywhere between $329,621 and $53,801……..now these are per “EPISODE” figures !!! Some patients can have more than one of these per year.
https://www.ajmc.com/journals/evidence- ... st-of-care

[kmall]

AML – New Findings…….

From my research contained in “Go Big or Go Home” and it’s focus on MDS, MF and AML – an underlying factor to a much higher Market Size Potential than originally estimated by Geron - $2.5 Billion (for MDS & MF), were much higher patient populations than projected. Anywhere from 1.5x to 2x would not be unexpected (links provided in Go Big or Go Home). As explained at the introduction: misdiagnosis, underreporting, pollution, and a decrease in median patient age in certain parts of the world have all attributed to discrepancies amongst patient estimates globally. This in turn can make a $1 Billion estimate, easily a $1.5 or $2 Billion dollar one. With that said I’ll provide some additional information on AML and try to gauge a ballpark figure on what we can expect.

A (2012) Bristol Myers Fact Sheet places Global incidence of AML at 350,000 patients. This is much, MUCH higher than expected and most likely more in line with findings from the factors listed above.
https://www.bms.com/assets/bms/us/en-us ... -sheet.pdf

Published in 2020 this BioMed Central article shines a light on the disproportionate Global increase in AML when compared to other leukemia’s
Leukemia incidence trends at the global, regional, and national level between 1990 and 2012 - June 2012
“A significant decrease in leukemia incidence was observed between 1990 and 2017. However, in the same period, the incidence rates of AML and CLL significantly increased in most countries, suggesting that both types of leukemia might become a major global public health concern.”
https://ehoonline.biomedcentral.com/art ... 20-00170-6

Along with a growth in patient population, comes an increasing economic strain placed on countries throughout the world. Many of these countries who have adopted subsidized Healthcare Systems are currently looking at alternative treatment options to alleviate this ballooning financial strain in their economies. A drug like Imetelstat could very well play a dual role here of treatment and cost savings, especially if used as Frontline. Perhaps the UK had this in mind with their recent announcement of Imetelstat being granted Innovation Passport for LR-MDS, which is the first prescribed entry point to the Innovative Licensing and Access Pathway (ILAP).
https://ir.geron.com/investors/press-re ... fault.aspx

Another BioMed Central article (2020) strikes at the heart of this issue of weighing increasing Global AML incidence rates in addition to a “mushrooming” economic burden.

The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017 – published June 8, 2020

“Globally, the incidence rate and mortality rate of AML were gradually increased. Males and elder people had a higher risk to develop AML. The incidence rate of AML was positively correlated to SDI values which meant the incidence rate in the developed region was significantly higher than in the developing region. In the meanwhile, the incidence rate in some developing areas such as the middle SDI and low-middle SDI countries increased rapidly. Smoking, high body mass index, occupational exposure to benzene, and formaldehyde were mainly risk factors contributing to AML-related mortality. There is plenty of room to control occupational exposure to carcinogens especially in developing countries. Generally, considering the accelerated aging trend in the globe, the incidence rate and mortality rate of AML might further increase. Therefore, the policy-marker should rationally allocate public health resources to relieve the mushrooming burden of AML.”
https://jhoonline.biomedcentral.com/art ... 20-00908-z


Here in the US the rising cost of cancer treatment is increasing at a rapid pace, however, AML has become one of the costliest, and in terms of initial treatment and EOL (End of Life) it now takes the #1 position as described below:
Cost of Cancer Treatment in US Could Rise by 34% by 2030 – June 25, 2020 – Marisa Wexler

“Costs were analyzed according to three phases of treatment: an initial phase (the first year of treatment), end-of-life care (EOL; the year before a patient’s death), and a continuing phase (everything in between).
Overall, average annual estimated cancer-related costs for these three phases were $42,000 for the initial phase, $5,000 for the continuing phase, and $105,000 for the EOL phase, with all in 2019-dollar values. For AML specifically, these values were $182,900, $21,000, and $239,400, respectively. AML had the highest initial and EOL costs of any cancer type.
In general, cancer treatment costs were higher for people diagnosed with more advanced disease.
For comparison, EOL costs were also estimated for controls (people who died of disorders other than cancer). EOL costs overall were significantly higher for cancer patients than for others ($105,000 vs. $23,500), and for AML specifically ($239,400 vs. $144,400).”
https://acutemyeloidleukemianews.com/20 ... 4-by-2030/

[kmall]

Let’s get sidetracked for a moment………here’s where things start to come full-circle for Geron and latest target indication of AML……….

On June 14 of this year, I posted a list on the YMB of HealthCare and Pharmaceutical Professionals who had wished Dr. Aleksandra Rizo “congratulations” and “well wishes” for the announcement of “First Patient Dosed in IMpactMF Phase 3 Clinical Trial in Refractory Myelofibrosis”:
https://www.linkedin.com/in/aleksandra- ... -activity/
https://ir.geron.com/investors/press-re ... fault.aspx

One of these who stood out from the crowd for me was Anna Forsythe of Purple Squirrel Economics……..
https://www.linkedin.com/in/anna-forsythe-3667143/
Anna Forsythe - "A results-oriented, highly motivated leader, with over 20 years of progressive experience in global product commercialization and strategic drug development combined with a solid history of achievement that includes health economics, patient reported outcomes, manages markets, pricing and reimbursement and KOL development covering multiple therapeutic areas. Experience spans primary care and specialty markets and working in large established and very small startup companies.
Specialties: Health Economics, Outcomes Research, Global Market Access and Pricing."
At the time, I found it somewhat intriguing that a strategic global product and drug development Specialist would acknowledge Imetelstat’s and Geron’s current achievement of first patient dosing in P3 IMpact (MF).

Here’s where the dots start to connect……….
Look at who the lead author is on this abstract 2 months prior to the Geron announcement for first patient dosed in P3 IMpact on 4/13/2021: Ana Forsythe, Purple Squirrel Economics

What Does the Economic Burden of Acute Myeloid Leukemia Treatment Look Like for the Next Decade? An Analysis of Key Findings, Challenges and Recommendations – Feb 9, 2021

“One of the large retrospective database studies on the economic burden of AML in the US before the approval of targeted agents (2008 to 2016) examined HCRU and direct costs in AML in a commercial payer database.10 The most expensive episodes of care were R/R AML ($439,104), HSCT ($329,621), induction IC ($198,657), consolidation IC ($73,428), and NIC ($53,081). Across all these groups, the main driver of cost was inpatient hospitalization, which accounted for about 70% of costs. AML symptoms and treatment toxicity were associated with higher costs, suggesting that less toxic alternatives to chemotherapy may help to control healthcare costs in AML.”
https://www.dovepress.com/what-does-the ... rticle-JBM

[kmall]

Let’s get back on track………so how do we define a Global Annual Market Revenue Stream Potential for Imetelstat in AML?
Since discrepancies are found in patient reporting in MDS, let’s assume the same in AML……we’ve also found this to be true in MF. Regardless, I would air on the side of being conservative. We know from Go Big or Go Home that Global MDS patient population is approximately double of what’s “recorded” here in the US and Europe and most likely higher in other parts of the world since many of the tools we use to gauge these estimates are basically non-existent there – for lack of a better term……here’s a link and an excerpt for a reminder……

^ Go Big or Go Home –
^ “Going back to discrepancies in numbers being registered or misdiagnosed, this 2015 abstract confirms what we know to be the case already.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553145/
“MDS prevalence is estimated to be 60,000 and –170,000 in the USA and projected to grow.”

What????.......so we are basing our future financial projections on a patient population here in the US of 60,000?……..here we have definitive proof that, that base number is in fact that. Base. It is most likely 2-3x that. Exactly where we had pinpointed most of these population projections when you start to lay out all of the growing evidence of a booming patient population globally. See why I’m thinking $2.5 Billion in MDS and MF is conservative now? It’s most likely $2.5 Billion just for MDS alone. I wouldn’t be surprised to see the global market size of Imetelstat actually top $5 Billion or more, given all indications applicable and the possible 2 year+ time frame to commercialization if we get a green light through early approvals. Of course, a lot of speculation on my part, but looking at surmounting evidence of escalating patient populations and costs of treatment, it doesn’t seem like that much of a stretch after all.”
^ “China with a population of 1.386 Billion could have an MDS patient population of 286,900* (US - 20.7 / 100,000) - that's almost 5x the US (60,000) and it's most likely much higher since pollution and non-registry play a large role in the increases in MDS patient populations found outside of "developed nations.”
*In my opinion the number in China is most likely 400,00 – 600,00 or greater when factoring in all of the above examples we have substantiated through recent findings.
**India with a population (1.38 Billion) almost equals that of China (1.386) Billion. It most likely mirrors China’s MDS patient population as well when factoring in the above discussion. These two nations combined could very well have an MDS patient population nearing 1 million or more. It’s easy to see why there has been a consistent uptick in revenue streams for those Pharmaceutical companies with approved Hematologic drugs quarter after quarter in “developed” nations – reeling in these “undeveloped” countries with astronomical potential would make a “paradigm shift” of epic proportions.”

So, let’s say there are easily 120,000 MDS patients globally (extremely conservative in my estimation), and then approximately 30% of MDS cases progress into AML…..that gives us about 36,000 patients. Trying to estimate the costs associated with Imetelstat would be almost impossible at this point for several reasons; the actual cost of Imetelstat itself to providers once finally commercialized and available, and the cost of treatment to patients since that varies in multiple categories. I would feel very comfortable adding at minimum another $1Billion to that potential. Again, for the record I believe it could be close to, if not double that. But that’s just speculation with a fair amount of research behind it. India and China alone could dwarf the 36,000 patients total estimate given here, to the tune of 5x or more.

I can go into numbers of patients and treatment cost, but AML is VERY expensive to treat and just giving a low estimate of the $42,000/patient in the “initial stage” of treatment, multiplied by 36,000 patients = $1,512,000,000.00
Of course, not all of that estimated cost would see its way into Geron’s Annual Revenue Stream, however, that’s just the “initial” stage cost of AML treatment and a low estimate for patients when considering number of treatments per year and the particular stages of treatment cost. The EOL stage for example can be as high as $105,000/patient. I’ve found patient “episode” costs of 3-5x that in the $300,000 - $500,000+ range. In conclusion, I think $1B is a very fair, conservative and comfortable estimate.

On the other end of the spectrum, the Bristol Meyers Squibb fact sheet mentioned at the top of this post suggests an AML Global Patient Population of 350,000. When we multiply that by $42,000 we get a staggering figure = $12,600,000,000.00. Not only does that 350,000 AML patient estimate far exceed what one may expect, buy it solidifies our argument of Global MDS estimates being far greater than realized. If Bristol Meyers estimates are more in line with reality, we are looking at a Global MDS population of well over 1,200,000.
Once again, too many factors at play here to pinpoint what Imetelstat can or will eventually carve up from any of these projections from a financial perspective, however, with Geron and Dr. Scarlett giving an updated increase in the Annual Market Potential for MDS and MS at $3B, and now with AML in the equation, I would feel quite comfortable expecting at least another $1B in AML for a total of $4B.

This is a very conservative figure and is moving closer in line to my original median ballpark figure of $8 - $10 Billion for the above 3 indications, when considering a far wider range of patients globally. With the additions of: India, Argentina, Colombia, Malaysia, Australia, Georgia, Singapore (all new countries for Imetelstat in Clinical Trials) in the current P3 IMpact (MF) Clinical Trial – Geron is seemingly doing just that.
https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=2

Now let’s take a look at Imetelstat’s Global Annual Market Potential in Lymphoid malignancies since we recently learned that a pre-Clinical program is being conducted at MD Anderson Cancer Center in Houston Texas, to try establishing Imetelstat’s role in targeting these diseases. -Kmall

[kmall]

Lymphoid Malignancies –

Geron is now conducting a Pre-Clinical program at MD Anderson Cancer Center to define the role of Imetelstat in Lymphoid malignancies which can potentially cover a vast number of cancers, including:

1. Non-Hodgkin Lymphoma (NHL) – 81,560 patients/yr in the US………. 743,176 (2018) people in the US living with NHL – 510,000 new cases Globally every year (2018)
https://www.cancer.org/cancer/non-hodgk ... stics.html
https://seer.cancer.gov/statfacts/html/nhl.html
https://pubmed.ncbi.nlm.nih.gov/30895415/

2. Hodgkin Lymphoma (HL) – 8,830 patients/yr in the US……..83,087 patients/yr Globally
https://www.cancer.org/cancer/hodgkin-l ... stics.html
https://gco.iarc.fr/today/data/factshee ... -sheet.pdf

3. Multiple Myeloma (MM) – 34,920 patients/yr in the US……..160,000 patients/yr Globally
https://www.cancer.net/cancer-types/mul ... 20lymphoma
https://pubmed.ncbi.nlm.nih.gov/3233597 ... er%20drugs

4. Chronic Lymphocytic Leukemia (CLL) – 20,000 patients/yr in the US……195,129 (2018) people in the US living with CLL – 60,000 patients/yr Globally (2016) - *global annual incidence is between <1 and 5.5 per 100,000 people. The incidence of CLL is approximately 4.2 cases per 100,000 people in the Western world.
https://www.mskcc.org/cancer-care/types/leukemias/types
https://seer.cancer.gov/statfacts/html/clyl.html
https://jhoponline.com/jhop-issue-archi ... rn%20world (download PDF – Reference 16)

5. Chronic Myeloid Leukemia (CML) – 9,110 patients/yr in the US……200,000+ people in the US living with CML - 34,179 patients/yr Globally
https://www.cancer.org/cancer/chronic-m ... in%20526,i
https://ehoonline.biomedcentral.com/art ... 0in%202017
https://www.hmpgloballearningnetwork.co ... c-imatinib

6. Acute lymphocytic leukemia (ALL) – 3,000 patients/yr in the US…………64,200 patients/yr Globally
https://www.mskcc.org/cancer-care/types/leukemias/types
https://ehoonline.biomedcentral.com/art ... 20-00170-6

7. Hairy Cell Leukemia (HCL) – 1,000 patients/yr in the US………*Estimates of annual incidence range between 1/213,000 - 1/2,860,000 worldwide
https://www.mskcc.org/cancer-care/types/leukemias/types
https://www.orpha.net/consor/cgi-bin/OC ... eukemia%20(HCLc,female%20ratio%20of%204%3A1

For starters, this is a lot of information to grasp right off the bat. Between which indications in this grouping Imetelstat would/could potentially target, to the total number of patients globally we could possibly expect Imetelstat to treat. In just these figures alone – which are most likely lower than today’s estimates since most studies here are from 2018 or earlier, we are looking at over 912,466 NEW cases every year. In the NHL patient base here in the US, you have 743,176 (2018) patients currently living with NHL. With a Global new case estimate of 510,000 patients/year (2018); if we apply the same Global percentage of patients currently living with NHL, we get a figure of 4,643,750 globally. Once again, as we’ve seen in MDS, MF and AML, discrepancies of Global patient populations are far greater than that of the US and in most Leukemia indications slightly if not significantly lower. Even if we presumedly cut that 4,643,750 patient figure in half, we get still get 2,321,875 patients globally (outside of the US) currently living with NHL. Add the US total of over 743,000 and we’re looking at over 3,064,000 patients worldwide. Not only is this figure staggering, but it would still seem to be a very conservative estimate given what we already know from definite findings. Bottom line is, the addition of Imetelstat to target Lymphoid Malignancies would be a tremendous boon financially for Geron.

[kmall]

Imetelstat has previously been studied in both Myeloma and Lymphoma:

Multiple Myeloma:
1. (2008) Safety and Dose Study of GRN163L and Velcade to Treat Patients With Refractory or Relapsed Myeloma
https://clinicaltrials.gov/ct2/show/stu ... =7&rank=35

2. (2010) Open Label Study With Imetelstat to Determine Effect of Imetelstat in Patients w/ Previously Treated Multiple Myeloma
https://clinicaltrials.gov/ct2/show/NCT ... w=2&rank=6

3. (2012) The Telomerase Inhibitor, Imetelstat, Rapidly Reduces Myeloma Cancer Stem Cells (CSCs) in a Phase II Trial. Huff CA, et al. ASH

Lymphoma:

1. (2011) Imetelstat Sodium in Treating Young Patients With Refractory or Recurrent Solid Tumors or Lymphoma
https://clinicaltrials.gov/ct2/show/NCT ... =3&rank=12

2. (2012) Imetelstat for Children With Refractory or Recurrent Solid Tumors and Lymphoma
https://clinicaltrials.gov/ct2/show/NCT ... =2&rank=10


The big question is now, where does Imetelstat stand in this entire “guess-ti-mation” analysis for future Global Annual Market Potential of Lymphoid Malignancies? I’ve come across quite a few links with patient cost of treatment, and as we’ve previously seen they can fluctuate quite a bit. I’ll try and break some of it down, if at all possible, and once again air on the side of being conservative.

First let’s take a quick look at these statistics from the Leukemia and Lymphoma Society:
General Blood Cancers
New Cases
• Approximately every 3 minutes, one person in the US is diagnosed with leukemia, lymphoma or myeloma.
• An estimated combined total of 186,400 people in the US are expected to be diagnosed with leukemia, lymphoma or myeloma in 2021.
• New cases of leukemia, lymphoma and myeloma are expected to account for 9.8 percent of the estimated 1,898,160 new cancer cases that will be diagnosed in the US in 2021.
Deaths
• Approximately every 9 minutes, someone in the US dies from a blood cancer.* This statistic represents approximately 158 people each day or more than six people every hour.
• Leukemia, lymphoma and myeloma are expected to cause the deaths of an estimated 57,750 people in the US in 2021.
• These diseases are expected to account for 9.5 percent of the deaths from cancer in 2021, based on the estimated total of 608,570 cancer deaths.
*Data specified for “blood cancer” include leukemia, lymphoma and myeloma, and do not include data for myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPNs).

Hodgkin (HL) and Non-Hodgkin (NHL) Lymphoma
New Cases
• About 90,390 people in the United States (US) are expected to be diagnosed with lymphoma in 2021 (8,830 cases of HL and 81,560 cases of NHL).
Prevalence
• There are an estimated 825,651 people living with, or in remission from, lymphoma in the US.
o There are 152,671 people living with or in remission from Hodgkin lymphoma
o There are 672,980 people living with or in remission from non-Hodgkin lymphoma
Deaths
• In 2021, an estimated 21,680 members of the US population are expected to die from lymphoma (960 HL and 20,720 NHL).

https://www.lls.org/facts-and-statistic ... s-overview

[kmall]

Now let’s try delving deeper into these Lymphoid Malignancies listed above in terms of patient populations and cost of treatment:

1. Non-Hodgkin Lymphoma (NHL) – 81,560 patients/yr US
- 743,176 (2018) people in the US living with NHL
– 510,000 new cases Globally every year (2018)

Global incidence of lymphoma
At the global level, the annual incidence increased gradually and there were 101,133 (95% UI, 87,968–118,746) incidences in 2017 and 72,937 (95% UI, 55,801–79,370) incidences in 1990 (Table 1, Additional file 1: Figure S1A).Oct 22, 2019

https://jhoonline.biomedcentral.com/art ... 019-0799-1


Lymphoma Patient Population in India
The age-adjusted incidence rates for NHL in men and women in India are 2.9/100,000 and 1.5/100,000, respectively.
https://www.karger.com/Article/Fulltext/447577


When looking at a country like India with its population of 1.38 Billion, it can have an estimated 30,360 new cases of NHL every year when averaging both the men and women medians above = 2.2/100,000. With a population almost 4x that of the US, is it really possible that they have about 60% fewer cases of NHL every year, or do we find ourselves back in the misdiagnosis/underreported category again?

Anyone starting to detect a pattern?

Here are a few abstracts and articles detailing costs associated with NHL globally:

Global Non-Hodgkin Lymphoma Therapeutics Market Report 2021: Market to Reach $8.1 Billion by 2027 - ResearchAndMarkets.com
https://www.businesswire.com/news/home/ ... arkets.com

Medical costs associated with non-Hodgkin's lymphoma in the United States during the first two years of treatment

“Results: Patients with aggressive (n = 356) and indolent (n = 698) NHL had significantly greater health service utilization and associated costs (all P < 05) than controls (n = 1068 for aggressive, n = 2094 for indolent). Mean monthly costs were 5871 dollars for aggressive NHL vs. 355 dollars for controls (P < 0001) and 3833 dollars for indolent NHL vs. 289 dollars for controls (P < 0001). The primary cost drivers were hospitalization (aggressive NHL = 44% of total costs, indolent NHL = 50%) and outpatient office visits (aggressive NHL = 39%, indolent NHL = 34%). For aggressive NHL, mean monthly initial treatment phase costs (10,970 dollars) and palliative care costs (9836 dollars) were higher than costs incurred during secondary phase (3302 dollars). The mean cost of treatment failure in aggressive NHL was 14,174 dollars per month, and 85,934 dollars over the study period.
Conclusion: The treatment of NHL was associated with substantial health care costs. Patients with aggressive lymphomas tended to accrue higher costs, compared with those with indolent lymphomas. These costs varied over time, with the highest costs occurring during the initial treatment and palliative care phases. Treatment failure was the most expensive treatment pattern. New strategies to prevent or delay treatment failure in aggressive NHL could help reduce the economic burden of NHL.”
https://pubmed.ncbi.nlm.nih.gov/16966264/

This 2020 abstract highlights the difference in cost of care and medications in treatment of indications in two countries distinctly different from each other in terms of population and Healthcare.


Cost of Lymphoma in US and India – July 2020
“Here, we have outlined the differences in availability and affordability of cancer drugs between India and the United States.
In conclusion, the advent of biosimilars has reduced the cost of and made treatment of CLL and lymphoma similar in the United States and India in terms of survival and patient quality of life. Innovative strategies would help expand access to other novel agents to patients in India as well. In addition, implementing the Doha Declaration, having compulsory licensing, capping drug prices, expanding insurance coverage, and making cancer care available to all people irrespective of their economic, social, racial, and geographical backgrounds would make treatment for cancer globally accessible.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392782/


As you can clearly see, multiple factors apply: Indolent vs. aggressive cost, hospitalization vs. out patient cost, initial treatment vs secondary phase costs and so on. What stands out to me from the above links is a mind blowing $8,100,000,000.00 Market place potential of NHL treatment cost by 2027. That’s just Non-Hodgkin’s Lymphoma. Like treatment costs for MDS, MF and AML a Lymphoid Malignancy like NHL is increasing year over year.

[kmall]

2. Hodgkin Lymphoma (HL) – 8,830 patients/yr US
- 83,087 patients/yr Globally


This 2017 article from the Cancer Network, Highlights the cost associated with Hodgkin Lymphoma in terms of 2015 dollars.
Relapsed, Refractory Hodgkin Lymphoma Has High Economic Burden of Care - October 13, 2017
“There is a high economic burden associated with the treatment of relapsed or refractory Hodgkin lymphoma. A recent study found that patients undergoing treatment for the disease incurred a median total all-cause cost of about $300,000.”
“According to the researchers, medications were the greatest driver of median monthly costs. Median medication costs were more than three times higher than median inpatient or outpatient costs…….”

https://www.cancernetwork.com/view/card ... n-lymphoma


A 2018 abstract focuses on Frontline Failure (FLF) patients with Hodgkin Lymphoma and a 5 year treatment plan/cost.
Real-world analysis of cost, health care resource utilization, and supportive care in Hodgkin lymphoma patients with frontline failure – Oct 2018

“Patients were characterized as FLF (those who restart, switch to any chemotherapy; had a hematopoietic stem cell transplant; or newly initiated radiation therapy [RT] after discontinuing FL) or non-FLF (those not considered as FLF). Direct health care utilization and expenditures were measured over both fixed and variable length follow-up periods and during FL therapy.”
“Average per patient per month (PPPM) costs were significantly higher for FLF patients during all follow-up (US$20,266 vs US$7,772, P<0.05). Annual total expenditures were significantly higher among FLF patients (US$198,388) vs non-FLF patients (US$37,549). FLF (vs non-FLF) patients had a significantly shorter duration of FL therapy (116 vs 131 days, P=0.024) and higher total PPPM expenditures during FL (US$29,040 vs US$16,369, P<0.05). Annual cost varied by failure type with those who failed due to restart incurring the highest cost (US$269,189) and those who switched incurring the lowest cost (US$46,951). FLF patients had a significantly greater utilization in every health care resource category during follow-up.”
Conclusion
“FLF (vs non-FLF) patients utilized substantially more health care resources and incurred a substantially higher economic burden. Over 5 years, FLF patients with at least two lines of treatment were projected to incur US$535,846 of health care costs. Further research is needed to determine optimal treatment that could reduce the risk of progression, need for treatment after FL, and enhance long-term clinical and economic outcomes.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6198880/

Just as in other indications, we see the annual HL treatment costs fluctuate from $198,000+ (2015) to $37,500+ (2015) in varying patient groups. Some can go as high as $269,000+ (2015). Let’s just take the 5 year average ($535,846/5 = $107,169) of the FLF patient group on a yearly basis and average that with the non FLF patient group ($29,040 vs $16,369 average = $22,704) for an approximate figure - for all intents and purposes. Doing this we get a “ballpark” figure of $65,000.00. Not exactly precise by any means, however, even if we considered these figures were from over 6 years ago, I’d bet we’re still well below the “average” cost of care for these patients. Doing these primitive and hypothetical math formulas, one would expect that the approximate total cost of care for the 8,300 patients here in the US to be 540,000,000.00. Globally we could multiply that MANY times over.

Where does Imetelstat fit into the cost treatment analysis of NHL and HL with a combined 2027 approximation of over $8.1 Billion for NHL and more than likely over $2B (2015) for a Global HL ballpark estimate? I would think that even a $1B potential would far undervalue Imetelstat in this landscape. Since we like playing conservative ball on team Geron, we’ll go with that. For the record, I see this being at least double, if not more.

As you can see, trying to sort through these figures and estimates is a bit of “guess” work on my part. Since that pattern will continue for the other 5 Lymphoid Malignancies listed above, I’ll simply post corroborating links associated with each and you can make your own assumptions if you wish. I’ll post my final projection below in terms of a conservative estimate and what I believe to be more in line with a greater numbers of patients than reported and associated costs thereof that we tend to find when we do a little more digging around. Simply put, the pre-clinical Lymphoid studies are a very long way out from being realized in terms of an actual Clinical Trial Design and as such what indications Geron decides, if any of these, to target relies on multiple factors as well. The number one being in my view, is the completion of P3 IMerge (MDS) and top-line data readout expected for the first half of 2023….(as of this writing there is now “talk” of a possible delay in the P3 CT IMerge completion date with a QT prolongation study including an additional 45 patients). And then of course the follow up P3 IMpact (MF). Taking a quick look under the hood at these Lymphoid Malignancies and their Annual Revenue Potential for a company like Geron, I suspect we could add a significant amount to the already $3B/yr projection from Dr. Scarlett.

[kmall]

3. Multiple Myeloma (MM) – 34, 920 patients/yr US
- 138,415 people in the United States (US) are living with or in remission from myeloma
- 160,000 patients/yr Globally
https://www.lls.org/facts-and-statistic ... s-overview

“The worldwide incidence of MM is currently 160,000, and mortality is 106,000. Age-standardized myeloma incidence varies between 0.54 and 5.3 per 100,000 and correlates with 1-MIR, patient empowerment, HAQ Index, and access to cancer drugs. The 1-MIR varies between 9% and 64% and is closely related to myeloma incidence, HAQ Index, patient empowerment, access to cancer drugs, and health care expenditures.”

Worldwide the 5 year prevalence of the disease is 2,10,697 or 4.3/1,00,000 population. In India it is 11,602 or 1.4/1,00,000 population. (2017)

“The median age in USA is 74 years as per SEER data, whereas in various single institute data across India it is 1-2 decades lower at around 52-61 years.

The worldwide Age Standardized Rate (ASR) for incidence of MM as per the GLOBOCAN/IARC data is 1.4/1,00,000 population accounting to 1,00,000 new cases every year. In the US as per the SEER data, the ASR for incidence is higher at 5.8/1,00,000 population accounting for 21,000 new cases each year. The ASR for MM incidence in India is 0.7/1,00,000 population amounting to about 6,800 new cases a year4,”

“Worldwide the 5 year prevalence of the disease is 2,10,697 or 4.3/1,00,000 population. In India it is 11,602 or 1.4/1,00,000 population. As per the SEER data the complete prevalence of MM in USA is around 71,000 cases 6 . The estimated mortality rate from MM worldwide is 72,453 which accounts for 1% of all cancer related deaths. In India it accounts for around 5,900 deaths every year 8 . The USA SEER data shows that the Age Adjusted Death Rate was 3.4/1,00,000 population.”

https://pubmed.ncbi.nlm.nih.gov/32335971/



Multiple Myeloma Incidence Increasing Worldwide, Especially in the US - July, 2018
From 1990 to 2016, incident cases of multiple myeloma increased by 126% globally, while deaths increased 94%. The US had the most incident cases and deaths.
In 2016, there were about 130,000 cases of myeloma, translating to an age-standardized incidence rate of 2.1 per 100,000 persons. Multiple myeloma caused 98,437 deaths globally, with an age-standardized incidence ratio of 1.5 per 100,000 persons.
That means from 1990 to 2016, incident cases of myeloma increased by 126% globally and deaths increased 94%. The researchers estimated that population growth contributed to about 40% of this increase, an aging world population contributed about 52.9%, and a rise in age-specific incidence rates contributed about 32.6%.
Australasia, high-income North America, and Western Europe had the highest age-standardized incidence ratio of myeloma. The United States had the most incident cases and deaths from myeloma.
https://www.cancernetwork.com/view/mult ... ecially-us

From the abstract and article above, the numbers of patients globally are at least 160,000. And rising exponentially. It wouldn’t surprise me to find vast discrepancies in patient population figures for Multiple Myeloma or in either the above indications of NHL and NL. With that said here are a few links of patient costs for Multiple Myeloma:

Medications
“If your doctor decides you need medication, the price tag of cancer drugs can be staggering. Cancer drug therapies often involve a combination of two or three medications rather than just one. In one study, the total cost of a multi-medication therapy for people with multiple myeloma -- before insurance -- ranged from about $74,000 to as much as $256,000.”
https://www.webmd.com/cancer/multiple-m ... -treatment

How to Treat Patients With Multiple Myeloma Cost-Effectively Without Compromising Outcome
A Conversation With S. Vincent Rajkumar, MD

According to a presentation by S. Vincent Rajkumar, MD, Professor of Medicine at the Mayo Clinic, Rochester, Minnesota, on the cost-effective treatment of multiple myeloma, during the First International Summit on Interventional Pharmacoeconomics, each new drug for myeloma costs between $150,000 and $200,000 per year. For carfilzomib, a second-generation proteasome inhibitor and a mainstay in the treatment of patients with relapsed or refractory disease, the cost per year for doses at 56 mg/m2 can reach $260,000.

“Unlike [other hematologic cancers] such as large B-cell lymphoma or Hodgkin lymphoma, where you give 6 months of treatment and you’re done for most patients, in myeloma, treatment is pretty much lifelong, continuous therapy, for 7 or 8 years or more, which is the median survival of the disease,” said Dr. Rajkumar. “And we don’t use these drugs alone; we use them in combination, which then increases the cost even more…. Quadruplets are up-and-coming options now, very similar to R-CHOP [rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone] for the cure [of non-Hodgkin lymphoma]. You are talking about a four-drug combination of monoclonal antibodies costing between $350,000 and $600,000 for 1 year of treatment.”

https://ascopost.com/issues/august-25-2 ... g-outcome/

Multiple Myeloma Treatment Cost
________________________________________
How Much Does Multiple Myeloma Treatment Cost?

• For Multiple Myeloma in particular, treatment[3] typically involves one or more of the following options: chemotherapy, which can cost $10,000 -$200,000 or more; radiation therapy, which can cost $10,000-$50,000 or more; stem cell transplantation, which typically costs $20,000-$60,000; and/or prescription drugs which can be expensive[4] , costing $4,000 or more for a month's supply, depending on the drug and dose needed. For instance, common multiple myeloma drug Bortezomib (Velcade)[5] , which is administered intravenously, costs $4,000-$8,000 per month, depending on dosing, while lenalidomide (Revlimid)[6] , costs $7,900 per month at a 21-out-of-28-day dosing.

• The Agency for Healthcare Research and Quality[7] reports that patients with multiple myeloma are typically hospitalized for 12 days at a cost of $28,700 total, or $2,500 per day.

• A study[8] on the economic burden of multiple myeloma found that of all cancers involving the bone, it has the highest mean cost per case after diagnosis: $132,615 per case compared with $88,402 for patients with breast cancer who developed metastatic bone disease and $65,287 for patients with lung cancer who developed metastatic bone disease.
https://health.costhelper.com/multiple-myeloma.html

Multiple Myeloma comprises of over 160,000 patients Globally and costs upwards of $200,000.00 or more a year to treat. Once again, we’re looking at another muti-$Billion Annual Market Potential.

[kmall]

4. Chronic Lymphocytic Leukemia (CLL) – 20,000 patients/yr US
- 195,129 (2018) people in the US living with CLL
– 60,000 patients/yr Globally (2016)

Economic Burden of Chronic Lymphocytic Leukemia in the Era of Oral Targeted Therapies in the United States – Jan 2017

“Oral targeted therapies represent a significant advance for the treatment of patients with chronic lymphocytic leukemia (CLL); however, their high cost has raised concerns about affordability and the economic impact on society.”

“The per-patient lifetime cost of CLL treatment will increase from $147,000 to $604,000 (310% increase) as oral targeted therapies become the first-line treatment. For patients enrolled in Medicare, the corresponding total out-of-pocket cost will increase from $9,200 to $57,000 (520% increase)”

https://www.ncbi.nlm.nih.gov/pmc/articl ... 0increase).

Here’s a recently published study from the Journal of Managed Care Special Pharmacy, showing the cost effectiveness of venetoclax (Ven) + obinutuzumab (G) in comparison to other available treatments for CLL.
Cost-effectiveness of a 12-month fixed-duration venetoclax treatment in combination with obinutuzumab in first-line, unfit chronic lymphocytic leukemia in the United States – Nov 2021

“CONCLUSIONS: Fixed-duration VenG for 12 months is a cost-effective first-line treatment option for unfit CLL patients compared with other available options and provides value for money to US health care payers at a threshold of $150,000 per QALY gained. Future studies with longer trial follow-up and more mature survival data may help to confirm longer-term cost benefits of VenG.”

https://www.jmcp.org/doi/full/10.18553/ ... 27.11.1532

Talk about timing……….remember just last week we learned that Imetelstat will be used in combination with Venetoclax in the treatment of R/R AML patients in a new Clinical Trial named TELOMERE.

• “The third new clinical program will evaluate imetelstat in combination with venetoclax or azacitidine in relapsed/refractory AML patients. Named TELOMERE, this investigator-sponsored trial has been designed to be conducted in two parts. The first part will be a dose finding study in approximately 20 patients with a primary endpoint of safety. Upon finding a recommended dose of the combination therapy, the next portion of the trial will confirm the safety of the recommended dose and evaluate the efficacy of the combination therapy. Approximately 50 patients will be enrolled into the second part of the trial and the primary endpoint is overall response rate. The Company expects TELOMERE to begin in the first half of 2022.”
https://www.geron.com/patients/clinical-trials/

We can clearly see from the two abstracts above and given a Global incidence rate of 60,000 patients/year, CLL with its annual costs of $100,000+ in some cases, the potential for Imetelstat and Geron in this indication could be very favorable as well.


5. Chronic Myeloid Leukemia (CML) – 9,110 patients/yr US
- 200,000+ people (2020) in the US living with CML
- 34,179 patients/yr Globally

Health Care Cost Associated With Contemporary Chronic Myelogenous Leukemia Therapy Compared With That of Other Hematologic Malignancies – (2021)

“Mean annualized costs for CML were $82,054 (ie, $25,471 [95% CI, $20,808 to $30,133] more than those for HEM and $74,993 [95% CI, $70,818 to $79,167] more than those for GEN); these differences were driven by pharmacy costs in the CML group.”

https://ascopubs.org/doi/abs/10.1200/OP ... nalCode=op

A 2020 article from the Journal of Clinical Pathways highlights the cost disparities here in the US and in other countries (India/Canada) when treating CML patients with new generations of tyrosine kinase inhibitors vs the new generic version of imatinib.

Economic Burden of CML Treatment in the US: Before and After the Availability of Generic Imatinib – Oct 2020

“….in 2016, the new generic version of imatinib. Generic meaning it's the same molecule structurally, because it can be replicated once the patent expired, and made available with the idea of bringing competition and hopefully improving access to patients who have difficulty or cannot afford these expensive drugs.
What happened then? Again, the generic was compared to these new generation, next generation. Again, no difference in mortality. The generic, when it was launched in 2016, was priced almost as high as the originator, around $140,000 for a year of therapy.
The other drugs, even more so, in some cases. Very different than the experience in Canada and the rest of the world. In India, this drug costs about $400 a year, not $146,000. In Canada, it's more, but it's less than $10,000 for a year of therapy with generic imatinib.
Where in the US, until recently, well over $100,000 for a year course of therapy. Enormous hardship, and again, the challenge has been that the US does not negotiate drug prices and clinicians are often driven to use the latest therapies, which, again, come with a high price tag.”
https://www.hmpgloballearningnetwork.co ... c-imatinib

[kmall]

6. Acute lymphocytic leukemia (ALL) – 3,000 patients/yr in the US
- 64,200 patients/yr Globally

Acute Lymphocytic Leukemia along with Multiple Myeloma are the costliest blood cancers to treat.
What to Know About Acute Lymphoblastic Leukemia Treatment – Aug 2021
“A 2018 report commissioned by the Leukemia & Lymphoma Society found that that the average cost of treating acute leukemia in the first year was $463,414 — almost three times higher than the average for all blood cancers. The average out-of-pocket expense for ALL was $5,147.
The average overall cost for all blood cancers was $156,845, and average out-of-pocket cost was $3,877.
This cost for acute leukemia is more for several reasons, particularly the number of transplants that are done, the amount of hospital stays, and the intensity of the treatment regimen.
In general, cost varies by type of cancer, and typically decreases over time.”
https://www.healthline.com/health/leuke ... tment#cost

This report from the Leukemia & Lymphoma Society, found within the article above, highlights the costs associated with ALL and MM as being the highest in any blood cancers to treat:

MILLIMAN RESEARCH REPORT – The Cost Burden Of Blood Cancer Care – Oct 2018

“Acute leukemia and multiple myeloma are the costliest blood cancers. In the month of diagnosis, acute leukemia patients report the highest costs billed by inpatient hospitals (six times that of other cancers). Acute leukemia patients also report the highest average allowed spending in the month of diagnosis (just under $120,000). By comparison multiple myeloma is the second costliest cancer in the month of diagnosis with an average allowed spending per patient of $28,000. Acute leukemia and multiple myeloma report the highest sustained post-diagnosis allowed spending, with average monthly costs over $10,000 in the second year following diagnosis.”

https://www.lls.org/sites/default/files ... 20care.pdf


7. Hairy Cell Leukemia (HCL) – 1,000 patients/yr in the US
- *Estimates of annual incidence range between 1/213,000 - 1/2,860,000 worldwide

By far the rarest of the cancers in this group, here is an overview of HCL from the National Cancer Institute.

https://www.cancer.gov/types/leukemia/p ... atment-pdq

HCL is not curable, and because of its rarity among patients, “treatment pathways and outcomes in the real-world setting are not well understood, particularly among large sample sizes and in the USA,” as this 2017 shows. However, next to ALL and HL, HCL has the lowest average mean/median age of diagnosis 55.6/56.0 years as all of the Lymphoid cancers listed above.


Adverse event rates and economic burden associated with purine nucleoside analogs in patients with hairy cell leukemia: a US population-retrospective claims analysis – Feb 2020
“Results
In total, 647 PNA-treated patients were identified (mean age: 57.1 years). Myelosuppression and OI (opportunistic infections) incidence were 461 and 42 per 1000 patient-years, respectively. Adjusted results indicated that those with myelosuppression had higher rates of hospitalization (47.4% vs 12.4%; P < .0001) and incurred higher mean inpatient costs ($23,517 vs $12,729; P = .011) and total costs ($57,325 vs $34,733; P = .001) as compared with those without myelosuppression. Similarly, patients with OIs had higher rates of hospitalization (53.8% vs 30.8%; P = .025) and incurred higher mean inpatient costs ($21,494 vs $11,229; P < .0001) as compared with those without OIs.”

https://ojrd.biomedcentral.com/articles ... 020-1325-9

Once again, expensive to treat here in the US, but in India you can go for HCL treatment to the tune of 93,600 Rupees or $1300US.

https://medsurgeindia.com/cost/hairy-ce ... -in-india/


Conclusion: Global Annual Market Potential for Lymphoid Malignancy

Covering multiple cancers, the Lymphoid category poses many obstacles in estimating what a company like Geron can expect in terms of Potential Revenue Stream. Focusing on just six of the seven: NHL, NL, MM, CLL, CML and ALL, I would put a more than conservative figure of $500,000,000.00 on each of these for a total of $3Billion. Again, quite conservative, considering any of these would most likely command much, much more……I would say at least $1Billion each.

If we take the latest projection from Geron of a $3B Market Revenue Potential with MDS and MF, and add our estimate of $1B for AML we get $4B. Now add another $3B for 6 of the 7 listed Lymphoid indications discussed here and I think conservatively Geron could POTENTIALLY see an approximate $7B Global Annual Market Revenue Stream.
Once again, the Lymphoid Malignancy studies as pre-Clinical are in their infancy and as such, far, far away from being realized in any form of Clinical Trial Design.

Now, I’ll go out on a limb here and take my earlier estimate of $8B - $10B for MDS, MF and AML from a year and a half ago with the research I’ve uncovered, and my “not so conservative stance” and add another $4B from the 6 Lymphoid indications we looked at for an updated estimate of a $12B - $14B Global Annual Market Revenue Stream Potential for Geron.

Hopefully, if nothing else, this gives some of you, as it has given me, a little more insight into what diseases fall under the Lymphoid category, patient populations thereof and some of the costs associated with those highlighted here. Not to mention that along the way we came across a “Purple Squirrel” and a Venetoclax combo (CML) connection with Geron and Imetelstat. In my opinion, Geron and MD Anderson teaming up to gauge Imetelstat’s potential role in targeting these indications is exciting on many fronts for both patients and investors. -Kmall

[kmall]

***Disclaimer......it appears as if 4 of the 5 links on the 2nd page of this post from "Go Big or Go Home" are no longer available or reroute altogether. This 2001 abstract from the Netherlands is the only current link available - https://pubmed.ncbi.nlm.nih.gov/11276372/

All other links should be available for review. Apologies for any inconvenience. -Kmall

[rccola335]

thanks for the detailed post - you put an incredible amount of work into that - so you are saying our shares should be worth more than 1.54 - i like it

[biopearl123]

Wonderful detailed post kmall. Kudos and many thanks. Some big numbers in there!