What do we know for sure at this point? And what can we speculate?

[biopearl123]

1. The second agreement requiring J and J to develop and commercialize a product remains in place.
2. There is a "key observation" noted by Scarlett. Speculation: The reason OS is prolonged is that transformation to AML is modified. Not much to say in absence of no CRs and one PR but there is substantial improvement in symptoms and spleen if you are one of the luck 10%.
3. The MDS data is good. Those patients who made 8 week TI have already met the primary end point so the numbers can't get worse, they can only improve (speculation:probably comparable to the original 13) as more patients cross the line to TI, only two or three bring up the numbers and there are several weeks for that to happen. We won't know until ASH.
4. In order to have broken (partially) the embargo abstracts had to have been submitted in the first place. Speculation there will be more abstracts re MOA and other uses e.g. AML
5. Janssen implied it wasn't about drug efficacy with their statement but a re prioritization. Even if they do re prioritize to a potentially better therapy I am unaware of a new therapy ready to start PIII in MDS or PIII.
6. AML on slide but under wraps.
7. Side studies discussed, never actualized as yet.
8.Compassionate use: Janssen must have considered it but knowing they at a late point in time they were going to walk could not put it into action (speculation) but Geron could.
9. Speculation: Scarlett is going to have a field day at ASH
10. Fact not speculation: I have taken it in the shorts (a little humor might be in order) with this stock.

I sincerely hope we will see recovery. Regards to all, bp

[pursang]

Thank You BP !

[1bordersooner]

Excellent analysis Bio!

[karagozoglu12345]

In the CC why did Scarlett choose to state "In the primary analysis, after median follow-up of 23 months, the median overall survival in the high-dose arm had not yet been reached " rather than directly stating MOS has not been reached as of a certain date? The former is confusing and does not seem to indicate any formidable trend in the data. May be I am overlooking some key point. I would appreciate it if anyone with a clinical trial or pharmaceutical research background shed more light on this.

[biopearl123]

You are so right. Scarlett has obfuscated the data so we really don't know what he means since most are not statisticians. Here's my take away right or not. 1. MOS has been met in the low dose arm and is between 19 and 23 months. 2. 50% or more of the patients in the high dose arm have been followed for at least 23 month mark and more than half of those evaluated are still alive. Thats the best I can do for now. Please if anyone has expertise in this area and can help please do.

[karagozoglu12345]

Another depressing Seeking Alpha piece. Your thoughts?

Geron's Biggest Problem Still Lies Ahead
Oct. 9, 2018 12:03 AM•GERN
Summary
Recently, Geron announced Janssen's intention to discontinue its partnership in the development of Geron's lead asset, Imetelstat.
In the same press release, Geron released discouraging data for Myelofibrosis.
Coupled with my prior musing over Imetelstat's prospects in Myelodysplastic syndrome, I have serious concerns over Imetelstat's prospects going forward.
All in all, I encourage investors to seek opportunities elsewhere.
Introduction

According to its website,

We are a clinical stage biopharmaceutical company focused on the development of a telomerase inhibitor, imetelstat, in hematologic myeloid malignancies.

Recently, Geron (GERN) announced Janssen's intention to discontinue its partnership in the development of Geron's lead asset, Imetelstat. The announcement derailed the momentum merely built from the anticipation of the announcement alone:


Chart courtesy of StockCharts.com

Imetelstat For MDS

Last month, I discussed Imetelstat's prospects in Myelodysplastic syndrome (MDS) compared to Acceleron's (XLRN) Luspatercept. After objective assessment, it is apparent that Luspatercept is the better drug for the indication.

Luspatercept appears to be the better drug for MDS than Imetelstat. I believe Luspatercept benefits from a more specific/appropriate MOA. This increases its likelihood of efficacy and decreases the chances of systemic issues. Because Luspatercept is given subcutaneously, this grants Acceleron with greater convenience. Acceleron will also benefit by likely being first-to-market for this indication.

Although Janssen cited the partnership discontinuation was simply "the result of a strategic portfolio evaluation and prioritization of assets within their portfolio," it would be naive of us to think Janssen still believes Imetelstat has great commercial prospects. Otherwise, it would not have discontinued the partnership.

Imetelstat For Myelofibrosis

Geron is also developing Imetelstat in a phase 2 clinical trial (IMBARK) in patients with intermediate- or high-risk Myelofibrosis (MF) refractory to a Janus Kinase (JAK) Inhibitor. MF is another blood disorder characterized by abnormal blood cell production and scarring. As a result, patients with MF often present with enlarged spleens. Primary treatment of MF includes JAK inhibitors. However, not all patients respond appropriately.

In the same press release announcing the partnership discontinuation, Geron released matured data for MF:

For the 9.4 mg/kg dosing arm (n=59), highlights from the primary analysis included a spleen response rate of 10% and a symptom response rate of 32%. No patients achieved complete remission, and one patient achieved partial remission. The safety profile was consistent with prior clinical trials of imetelstat in hematologic malignancies, and no new safety signals were identified. The most common adverse events were cytopenias. At the time of the primary analysis, median overall survival had not been reached after 23 months of median follow-up.


Reduction in spleen size suggests the drug is active in the treatment of MF. One partial response and zero complete responses are good for an overall response rate [ORR] of 1.7% (n=59). Geron mentions the safety data is similar to that seen in previous Imetelstat trials (which aren't great).

Granted, these patients are a difficult-to-treat population considering their disease was refractory to first-line treatment, so we can expect numbers to be somewhat low. However, numbers this low suggests the drug is not active in treating this particular disease. Furthermore, the side effects associated with Imetelstat elicit a very unfavorable risk/reward profile for these patients.

Compare the matured data to what Geron in 2014 described as "unprecedented remissions" from a single-site:


Source: Geron 2014 ASH Presentation

The efficacy described above and the safety issues typically associated with Imetelstat suggests this drug is not at all effective in the treatment of MF. Geron will have a very difficult time advancing this drug for this indication if the current data doesn't improve drastically.

Past Imetelstat Failures

In 2012, Geron announced sobering Imetelstat news for two indications. Imetelstat, in a clinical study for treatment of breast cancer, was discontinued because "median progression-free survival in the imetelstat arm was shorter than in the comparator arm." Geron also mentioned that Imetelstat wouldn't progress to a phase 3 trial in NSCLC due to a lack of efficacy in a phase 2 trial.

Granted, these failures are in the past and have, arguably, very little to do with current prospects in indications like MDS and MF. However, I cannot help but think MDS and MF will be added to the basket of failed Imetelstat indications. As a nurse writing on such events, I have to weigh the necessitation of clinical trial with the safety and holistic well-being of subjects. I, therefore, have to ask: how long can we, ethically, trial this drug towards at-risk and very sick patients given the overt lack of efficacy and abundance of safety issues? The question warrants serious consideration.

Summary

Geron's biggest problem is not in Janssen's discontinuation of their partnership, but, rather, still lies ahead. Imetelstat, partnered or not, does not appear to be a viable drug for the treatment of either MDS or MF. The drug does not appear entirely effective nor safe. It does not provide therapeutic differentiation. Considering Imetelstat is the only drug in Geron's pipeline and MDS/MF are the only indications Imetelstat is seeking, Geron may be in for more pain going forward.

[biopearl123]

My response? Choose whom you wish to believe, Dr. Raza, Dr. Steemsa or the author of this article. To drag up solid tumor failures of the distant past is interesting. The focus is on heme now. Three weeks to abstract release, seven weeks to ASH. At that point Dr. Scarlett will have to provide clarity. If you can't wait that long, its understandable given the melt down. bp

[rinconj]

That MF article about the failures in breast cancer and other solid tumors seems to be one of the many conflicting results I've read about Imet. It's true that Geron stopped their breast cancer trials due to lack of efficacy in 2012, but why are we seeing positive results from other more recent papers like the following? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4667948/


Sdrawkcabeman said he thought JNJ never considered using Imet with solid tumors as the reason for dropping Imet on his recent twits. So do Imet has a chance with solid tumors or not?