Imetelstat Trial Update Lift Geron, Despite Indecision By Partner J&J
Executive Summary
News of continuation of myelofibrosis and myelodysplastic syndromes studies well-received in market, despite global partner J&J's apparent reluctance to commit to imetelstat for the long haul.
Geron Corp.'s clinical update news that studies of the telomerase inhibitor imetelstat will carry on in lower risk myelodysplastic syndromes and relapsed/refractory myelofibrosis gave the company a boost in the market, even though partner Johnson & Johnson has not committed to more advanced development.
The Phase II/III IMerge study of lower risk myelodysplastic syndromes (MDS) will continue with some revisions, subject to approval by the US FDA, and the Phase II IMbark of relapsed/refractory myelofibrosis (MF) will carry on with no changes, based on a new internal data review, Geron announced April 10.
The company's stock price rose by 19.53% on the news, closing at $2.57, even though global partner Janssen Pharmaceutical Cos., a J&J company, has not committed to development over the longer term.
Geron has been partnered on imetelstat (GRN163L) with Janssen since November 2014; the deal included an upfront payment of $35m and up to $900m in milestone payments and gave Janssen worldwide development and commercialization rights in oncology, including hematologic malignancies. [See Deal]
Per the agreement, Janssen needs to make a decision about moving forward with development after a Phase II analysis or after the start of Phase III within a certain time period.
A joint steering committee for the collaboration is reviewing the data and Janssen will consider their assessments and the evolving competitive landscape in deciding whether to stay on board. Janssen has the ability to terminate the deal at any time for any reason – the company can't "specifically cherry-pick indications," but it can recommend changes to trial design along the way, Geron CEO John Scarlett clarified during an April 10 investor call.
Change Ahead For IMerge
The three-part IMerge study tests imetelstat in transfusion-dependent, lower risk MDS patients who relapsed or were refractory to erythropoiesis-stimulating agents (ESAs).
The latest review of the trial by the joint steering committee included an evaluation of 30 patients who participated in the single-arm, open-label first portion. This review found that safety was consistent with prior trials and that there were no new safety signals.
"The benefit/risk profile of imetelstat, including assessments of eight-week and 24-week transfusion independence and hematologic improvement by erythroid (HI-E) response, across multiple MDS subtypes, supports continued development in lower risk MDS," according to Geron.
The first part will continue with no trial design changes but the companies will submit suggested "refinements" to FDA for the next leg of development, a randomized, controlled Phase II study of 170 patients.
Janssen will consider the outcome of the submission to FDA, along with the status of overall development and data, in deciding whether to stay on board for Phase II. If all goes well, the Phase III part of the study could start in the fourth quarter.
IMbark is a Phase II study that tested two doses in patients with intermediate- to high-risk MF after prior treatment failure with a JAK inhibitor. Geron announced in September 2016 that the study design was being changed when it became clear that the lower dose – 4.7 mg/kg every three weeks – was not sufficiently efficacious and the higher dose – 9.4 mg/kg every three weeks – was appropriate. (Also see "Imetelstat Study Blip Beats Geron’s Shares Down" - Scrip, 14 Sep, 2016.) Patients were switched to the higher dose and enrollment has closed.
The joint steering committee's review of data for about 100 patients found safety consistent with other studies, Geron said. "In addition, the data suggest a potential overall survival benefit associated with imetelstat treatment in these patients," the company said.
Janssen's decision about proceeding with development will be informed in part by an assessment of more mature data from the study and is expected within the next year.
Focus On Unmet Need
CEO Scarlett highlighted areas of high unmet need for both conditions during the company's April 10 call. Patients with MDS have chronic anemia and treatment effects of ESAs don't last, the exec noted.
"As a result, many patients become dependent on frequent red blood cell transfusions to manage symptoms of anemia and fatigue. Transfusion dependency is associated with poor survival, in part because patients develop life-threatening iron overload or toxicity. This underscores the critical need for new therapies that target the underlying malignancy, as well as therapies that manage symptoms," Scarlett said.
The pace of new drug development in MDS is "really quite modest," the exec said.
As for myelofibrosis, the only drug approved for that indication is Incyte Corp.'s Jakafi (ruxolitinib) and most patients eventually fail treatment, he noted.
"Long-term follow-up from clinical studies of ruxolitinib suggests that approximately 75% of patients have discontinued treatment by five years with suboptimal response or loss of therapeutic effect cited as major reasons," Scarlett said.
Data from Janssen suggest median survival after relapse on a JAK inhibitor is only seven months. Everyone understands the point that once patients are out of luck with JAK inhibitors, there is nothing else for them to try, he said.
"So that unmet medical need is crystal clear and it empowers us to continue studying the disease," Scarlett said.
Geron is using a strict definition of relapsed or refractory, and data are limited in terms of what kind of outcomes to expect with a new agent in this patient population. The company is the only sponsor studying true relapsed refractory patients with MF, Scarlett maintained.
Geron feels very good about continuing development in both populations and Janssen's decision to continue will take into account the evolving treatment and competitive landscape, he said.