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Summary

  • Mouse and monkey animal studies revealed no liver damage or elevated liver enzymes following Imetelstat treatment.
  • Mayo Clinic is submitting all relevant Imetelstat efficacy and follow-up data in Myelofibrosis study to FDA to release partial hold.
  • Dr. Tefferi from Mayo Clinic will present data regarding Imetelstat response in acute myelogenous leukemia and refractory anemia with ringed sideroblasts at ASH conference in December 2014.

Geron (NASDAQ:GERN) stock has been in a holding pattern between $1.8-2.5 a share since the FDA placed a clinical hold on Imetelstat clinical trials in early March pending more information regarding the low grade liver function test (LFT) abnormalities observed with extended treatment in the Essential Thrombocythemia (ET) trial. On Thursday, Geron provided an update to investors on the progress of gathering the data requested by the FDA to lift the hold and additional steps they may take to expedite starting a Phase II clinical trial in Myelofibrosis. On the call, Geron CEO Dr. Scarlett stressed that the FDA placed the full clinical hold not on Myelofibrosis but on the Geron sponsored ET trial in which patients had been on the drug continuously for up to 3 years. Importantly, with long-term treatment, there was no further progression of LFT abnormalities and no patients ever ceased Imetelstat treatment due to liver complications. It was reiterated that since ET patients are already treated sufficiently and the disease does not drastically affect survival, this trial was conducted as a proof of principle study and Geron has no intention of using Imetelstat for ET treatment. Their focus is solely on those myeloproliferative disorders in which there is a severe unmet clinical need such as Myelofibrosis, where the risk/reward profile is extremely advantageous.

The FDA has placed a partial clinical hold for the Mayo Clinic Myelofibrosis trial headed by world renowned hematologist Dr. Ayalew Tefferi, allowing those patients receiving clinical benefit to remain on the drug. Again, I view this as being a very good sign that the FDA realizes the benefits of the drug outweighs any risks for those responding as this was not the case for those responding in the ET trial. In the Myelofibrosis trial, a subset of patients experienced complete and partial responses following Imetelstat treatment, something no drug has ever done. Making this even more impressive is that the trial enrolled only Intermediate and High-risk Myelofibrosis patients in which there are currently no effective treatment options available and the average lifespan is 1-3 years. Does a clinical hold by the FDA for low level LFTs that don't progress over time make sense for this disease?

To provide the follow-up data to determine if low grade LFT abnormalities resolve back to baseline after drug removal, Geron is currently getting the required institutional review board (IRB) approval to allow for the LFT follow-up studies in the ET patients. Again, since many patients who were previously in the ET trial have been long removed some of this data may be difficult to get, but Dr. Scarlett indicated that having follow-up data for every single patient will likely not be required by the FDA. The animal studies that the FDA requested regarding LFT abnormalities observed following Imetelstat treatment has been collected and analyzed. Geron as well as several outside liver experts who have reviewed the data could not find any evidence of liver damage or elevated LFTs in mice or monkeys. From Dr. Scarlett's comments, it appears there has yet to be any major conversations between Geron and the FDA regarding the hold. Typically, all the data asked for by the FDA that can be collected is compiled and submitted before any discussions regarding the hold take place and concerns addressed. During this data submission is when Geron would provide the FDA their intentions to only pursue Imetelstat in Myelofibrosis and other unmet disorders and the FDA can make the determination based on the risk/reward profile. It is very likely the FDA will allow Imetelstat to progress once they are provided the full picture.

In parallel Geron is also contemplating initiating trials in Europe. This would enable Geron to begin gathering data and further characterize the efficacy of Imetelstat in Myelofibrosis in the chance the FDA extends the hold.

The Mayo Clinic

One of the biggest supporters of Imetelstat in Myelofibrosis is Dr. Tefferi. Since there are no effective treatments for Intermediate and High-Risk Myelofibrosis patients, you could imagine why he would be excited about a drug that has produced complete responses for the first time ever. His mission now is to further characterize Imetelstat and determine what makes the drug effective in some patients and not others. During the call, Dr. Scarlett stated that Dr. Tefferi assured him that he is submitting all the LFT data the FDA is requesting to release the partial clinical hold in addition to all the efficacy data. Importantly, there has been very little mention by Dr. Tefferi in his presentations and abstracts regarding low level LFTs being a concern. Interestingly, Dr. Scarlett mentioned in the update that it could be possible that Myelofibrosis patients have higher baseline LFT readings than ET patients and therefore elevations may not be relevant in this population. In addition, Dr. Tefferi has detailed that he will be releasing additional data at the American Society of Hematology (ASH) Annual Meeting in December 2014 in patients with refractory anemia with ringed sideroblasts, or RARS, and patients with myelofibrosis that has transformed into acute myelogenous leukemia, known as blast-phase myelofibrosis and their responses to Imetelstat. Positive data in these patients, which is very likely, would expand the indication of Imetelstat and provide a major catalyst for the stock.

Conclusion

Geron and the Mayo Clinic continue to work in parallel to gather the necessary data to provide the FDA on LFT abnormalities. Although, Geron may be delayed in gathering all the ET data as they need IRB approvals, etc. The Mayo clinic is already preparing all the Myelofibrosis efficacy data and the LFT follow-ups requested. It is highly likely that this data alone will satisfy what the FDA is seeking to release the partial clinical hold and allow Geron to continue trials in Myelofibrosis with a plan to track LFT abnormalities closely. To pad the risk even more they are sitting on over $150 million in cash following a recent public offering at $4/share. This will allow Geron to fund the appropriate clinical trials either in the US, Europe or both. There is also a strong possibility that they partner to further progress Imetelstat development. Expect a lot of volatility as short-term investors pop in and out of the stock. It is unlikely investors will know when Dr. Tefferi submits his data to the FDA so don't be caught on the sidelines when the Myelofibrosis partial hold is lifted and the stock has tripled in value.

Source: Geron And The Mayo Clinic Working In Parallel To Release Clinical Hold Of Imetelstat