PR July 31, 2017: Geron Announces Updates to Imetelstat Clinical Development

[Fishermangents]

Geron Announces Updates to Imetelstat Clinical Development
Conference Call Scheduled for 8:00 a.m. ET on Tuesday, August 1

MENLO PARK, Calif., July 31, 2017 (GLOBE NEWSWIRE) -- Geron Corporation (Nasdaq:GERN) today announced updates to the clinical development plans for IMerge and IMbark, the ongoing trials of the telomerase inhibitor imetelstat in lower risk myelodysplastic syndromes (MDS) and relapsed or refractory myelofibrosis (MF), respectively, being conducted by Janssen Research & Development, LLC. For IMerge, Part 1 will be expanded to enroll additional patients in a refined MDS population to confirm the clinical benefit and safety observed from current results. For IMbark, the trial remains unchanged. Geron expects that the IMbark protocol-specified primary analysis, the completion of which triggers a future Continuation Decision by Janssen, will begin no later than the third quarter of 2018.

IMerge

Original Trial Design
IMerge (NCT02598661) is a Phase 2/3 clinical trial evaluating imetelstat in transfusion dependent patients with Low or Intermediate-1 risk MDS who have relapsed after or are refractory to prior treatment with an erythropoiesis stimulating agent (ESA). The clinical trial is in two parts: Part 1 is a Phase 2, open-label, single-arm design in approximately 30 patients and Part 2 is designed to be a Phase 3, randomized, controlled trial in approximately 170 patients. The primary efficacy endpoint is the rate of red blood cell (RBC) transfusion independence (TI) lasting at least 8 weeks.

Trial Status Update
In Part 1 of IMerge, 32 patients were enrolled, of which a subset of 13 patients had not received prior treatment with either a hypomethylating agent (HMA) or lenalidomide and did not have a del(5q) chromosomal abnormality. As of May 2017, the 13-patient subset showed an increased durability and rate of transfusion independence compared to the overall trial population (≥8-week RBC-TI: 53.8% vs 34.4%). The safety profile in Part 1 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, which were manageable, and included grade 3/4 neutropenia and thrombocytopenia.

Based on these data from the 13-patient subset, the Joint Steering Committee has decided to amend Part 1 of the protocol to enroll approximately 20 additional patients who are non-del5q and naïve to HMA and lenalidomide treatment in order to increase the experience and confirm the benefit-risk profile of imetelstat dosed at 7.5 mg/kg every four weeks in this refined target patient population. Enrollment into the expanded Part 1 is expected to begin in the fourth quarter of 2017.

Separately, a data package and proposed refinements to the trial design for Part 2 of IMerge were previously provided to the FDA following an internal data review completed by Janssen in April, and related interactions are ongoing. Feedback from ongoing FDA interactions, data from the expanded Part 1, and other imetelstat program information, including the protocol-specified primary analysis for IMbark, are expected to inform Janssen’s decision of whether to move forward to Part 2 of IMerge.

Detailed results for the original 32 patients in Part 1 of IMerge, including key secondary endpoints of hematologic improvement and rate of RBC-TI lasting at least 24 weeks, as well as duration of response and detailed safety information, will be submitted for presentation at a major medical conference.

IMbark

Trial Status Update
IMbark (NCT02426086) is a Phase 2 trial in patients with Intermediate-2 or High Risk MF who have relapsed after or are refractory to prior treatment with a JAK inhibitor. The trial continues without modification, and patients remaining in the treatment phase may continue to receive imetelstat. All safety and efficacy assessments will be conducted as planned in the protocol, which includes an assessment of a potential survival benefit associated with imetelstat treatment. To date, median overall survival has not yet been reached in either the 4.7 mg/kg or 9.4 mg/kg dosing arm. Enrollment of new patients to the trial remains suspended because the total number of patients enrolled to date is adequate to perform the protocol-specified primary analysis. Geron expects Janssen to perform an internal data review in the first quarter of 2018 to enable a potential protocol amendment to allow the long-term treatment and follow-up of patients, including for survival, beyond the current April 2018 per-protocol end-of-study date.

Continuation Decision
The Joint Steering Committee has agreed that the timing of the protocol-specified primary analysis for IMbark will begin upon the earlier of either a pre-specified number of deaths occurring in the trial or the end of the third quarter of 2018. Following completion of this primary analysis, which includes an assessment of potential survival benefit associated with imetelstat treatment, Janssen will notify Geron whether it elects to maintain the license rights and continue the development of imetelstat in any indication, i.e., the Continuation Decision.

Conference Call
At 8:00 a.m. EDT on August 1, 2017, Geron’s management will host a conference call to discuss these updates to imetelstat clinical development. Participants can access the conference call live via telephone by dialing 877-303-9139 (U.S.); +1-760-536-5195 (international). The conference ID number is 42220500. A live audio-only webcast is also available through the company’s website at http://www.geron.com in the Investors section under Events and at http://edge.media-server.com/m/p/oqg6hyn5. The audio webcast of the conference call will be available for replay approximately one hour following the live broadcast through September 1, 2017.

Link: http://ir.geron.com/phoenix.zhtml?c=673 ... ID=2290347

[Fishermangents]

Response from Hoosier on SA on the press release:

1) Lenalidomide's MDS approval is limited to patients with a deletion 5q cytogenetic abnormality. Lenalidomide's safety and efficacy were demonstrated in one single-arm, multicenter clinical trial of 148 patients. The primary endpoint was RBC transfusion independence response (an eight-week or longer transfusion-free period). RBC transfusion independence response was observed in 67 percent (99/148) of patients in the trial. The median RBC transfusion response duration was 44 weeks (range of 0 to > 67 weeks).

2) The 5q del abnormality confers a good prognosis, is associated with normal or elevated platelet counts, and is found in ~15% of MDS patients.

3) Janssen is steering Imetelstat towards the non-5q del population....which has an unmet need as Lenalidomide's approval is limited to the smaller 5q del population.

4) Approximately 85% of the MDS patients are in the non-5q del subgroup. This is still a sizable patient population.

5) It appears both the Low and Int-1 patient subgroups are still in play. These subgroups represent ~70% of all MDS patients.
The revised IMET patient population math would be as follows.......
IMET Subgroup = (60,000)*(0.70)*(0.85) = 35,700 patients (existing population)
IMET Subgroup = (12,000)*(0.70)*(0.85) = 7,140 patients (new patients / year)

[Fishermangents]

Second comment from Hoosier on SA today:

1) Our 'good problem to have' within IMbark continues as patients remain alive to the extent they can't assess median overall survival. This has been the source of delay in the IMbark primary analysis and subsequent Continuation Decision. Again, it's a good problem to have.

2) Geron/Janssen agreed upon a deadline (end-3Q18) for the IMbark primary analysis and subsequent Continuation Decision.....in the event we still don't have a median survival established for the IMbark trial. This ends the uncertainty regarding the continuation decision. The key question with IMbark seems to be whether Janssen will have sufficient response data to pursue an Accelerated Approval, or whether we'll need a Phase 3 for R/R MF patients before seeking approval. Either way represents a path forward (good news) with one path being obviously more desirable.

3) Delaying the start of the MDS Phase 3 is the undesirable aspect. It would be nice if they could go straight to Phase 3 based on the subgroup (7 of 13) of patients that demonstrated higher TI response rates and in Part 1 of the IMerge trial. However, I doubt the FDA would approve launching a Phase 3 based on such a low patient population, and it's a good business decision to run a quick confirmation study involving 20 patients....with the preliminary results further informing (but not delaying) Janssen's 2018 continuation decision.

4) Based on Dr. Scarlett's comment, it appears being naïve to HMAs and Lenalidomide is more important than the 5q del aspect. This is a very interesting observation that suggests we could find ourselves positioned in front of HMAs and/or Lenalidomide treatments for Lower risk MDS patients. It will be interesting to better understand the response data (and observations) presented at this year's ASH meeting.

5) It's difficult to see / understand the stock price sinking when the preliminary IMbark and IMerge data is indicating two paths forward for approvals (with or without Janssen). The expected timing of future events seems the culprit for the sell-off as one could argue the probability of future approvals remains the same (or has increased) based on the recent update. An overall TI response rate of 32% is good news as Dr. Scarlett stated this morning (and aligns reasonably well with Tefferi pilot study results) while a 54% TI response rate in a sizable subgroup (with unmet need) is definitely good news.

6) Also, with Janssen confirming Imetelstat's activity in MF and MDS patients, there's reason to believe Dr. Tefferi's pilot study results can be duplicated in frontline MF patients. I remain disappointed we don't have a frontline MF trial running at this point. Geron won't independently start such a trial because frontline MF is an indication of interest to Janssen. However, Janssen won't start such a trial until after they've made their continuation decision. Thus, we (and patients) sit and wait. This scenario doesn't align with JNJ's 'patients first' credo in my opinion.

(01 Aug 2017)