Karyopharm Therapeutics Inc (NASDAQ:KPTI), a clinical-stage pharmaceutical company, today reported positive top-line results from its Phase 2b STORM study evaluating the activity of selinexor (KPT-330) in multiple myeloma (MM). Selinexor, the Company’s lead, novel, oral Selective Inhibitor of Nuclear Export / SINE™ compound, is being developed for the treatment of a variety of malignancies, including MM. Karyopharm also provided an overview of the planned development path for selinexor in MM.

The Phase 2b STORM study is a single-arm clinical trial evaluating selinexor in combination with low-dose dexamethasone in heavily pretreated MM patients, meaning patients with quad-refractory disease or penta-refractory disease. Patients with quad-refractory disease have previously received two proteasome inhibitors (PIs) (bortezomib (Velcade®) and carfilzomib (Kyprolis®)) and two immunomodulatory agents (IMiDs) (lenalidomide (Revlimid®) and pomalidomide (Pomalyst®)), and their disease is refractory to at least one PI, at least one IMiD, and has progressed following their most recent therapy.  Patients with penta-refractory myeloma have quad-refractory disease that is also refractory to an anti-CD38 monoclonal antibody, such as daratumumab (Darzalex™) or isatuximab.

Among the 78 evaluable patients (median seven prior treatment regimens), the overall response rate (ORR) was 20.5% based on Independent Review Committee adjudication, including very good partial responses (VGPR) and partial responses (PR).  Among the 48 patients in the quad-refractory group, the ORR was 20.8%. For comparison, in a similar quad-refractory patient population, Darzalex had an ORR of 21% and isatuximab had an ORR of 20%.  Among the 30 patients in the penta-refractory group, the ORR was 20.0%. Several patients remain on study, including those with VGPRs, PRs and minor responses. To the Company’s knowledge, no agent has previously shown activity in this penta-refractory population. The side effect profile for selinexor was consistent with previous trials, and no new safety signals were identified. Additional data will be presented later this year.

Keith Stewart, MB. ChB., Anna Maria and Vasek Polack Professor of Cancer Research at the Mayo Clinic and lead investigator of the STORM study, said, “Although treatment of multiple myeloma has improved dramatically, eventually many patients will develop refractory disease, no longer responding to any of the immunomodulatory agents and proteasome inhibitors commonly used (quad-refractory).  These patients will also eventually progress on anti-CD38 monoclonal antibodies, which we refer to as penta-refractory disease. These are clearly the patients with the highest unmet need, as they have no remaining viable treatment options. The STORM data are compelling because they demonstrate that oral selinexor achieves a 20.8% response rate in the quad-refractory group, similar to recently reported intravenous anti-CD38 therapy results in the same patient population. Selinexor also achieves an equally notable 20.0% response rate in the penta-refractory group, with the significant advantage of oral administration.  We are currently unaware of any other therapy, oral or intravenous, reporting such activity in these difficult-to-treat patients who have exhausted all available therapies.”

In addition to the STORM study, Karyopharm initiated the Phase 1b/2 STOMP (Selinexor and Backbone Treatments of Multiple Myeloma Patients) study to evaluate selinexor in combination with existing therapies across the broader population in MM. In the arm evaluating the combination of selinexor, bortezomib and dexamethasone, dose escalation has been completed and the recommended dose has been determined, providing a basis for the randomized Phase 3 “BOSTON” study described below.

Sagar Lonial, MD, Professor and Chair, Department of Hematology and Medical Oncology, Emory University School of Medicine and Chief Medical Officer, Winship Cancer Institute of Emory University, commented, “Myeloma continues to be an incurable blood cancer in most patients and our main goal in treating refractory disease is to induce responses and maintain them as long as possible. In addition to these new data with oral selinexor and low-dose dexamethasone, the emerging clinical data from selinexor in combination with bortezomib, including in proteasome-inhibitor refractory disease, suggests a synergistic effect and favorable safety profile. These data are quite exciting and will form the basis for future studies.”

Selinexor: Multiple Myeloma Clinical Development Plans and Timelines

Based on these positive top-line STORM data and existing unmet medical need, Karyopharm plans to implement the following clinical development initiatives focusing on obtaining regulatory approval of selinexor in MM:

  • Karyopharm is expanding the STORM study to include approximately 120 additional patients with penta-refractory MM. To the Company’s knowledge, this will be the largest study ever undertaken in this patient population. Assuming a positive outcome and remaining unmet medical need, Karyopharm intends to use the data from the expanded STORM study to support a request that the FDA consider granting accelerated approval for selinexor in MM. The Company anticipates reporting top-line data from the expanded cohort in early 2018.
  • The FDA instituted its Accelerated Approval Program to allow for expedited approval of drugs that treat serious conditions and that fill an unmet medical need based on a surrogate endpoint or an intermediate clinical endpoint thought to predict clinical benefit, like ORR. Accelerated approval is available only for drugs that provide a meaningful therapeutic benefit over existing treatments at the time of consideration of the application for accelerated approval, which the FDA has reiterated in its feedback to the Company. Particularly in disease areas with multiple available and potential new therapies, such as MM, accelerated approval carries a high regulatory threshold. Drugs approved under the Accelerated Approval Program are also typically required to be studied in randomized confirmatory trials on a post-approval basis to confirm clinical benefit.  Given the number of approved and experimental therapies in development to treat MM, and consistent with its standard guidance, the FDA has recommended that the Company conduct a randomized study geared towards full approval, which the Company is planning with the BOSTON study discussed below.  In addition, to the Company’s knowledge, no other studies are currently being conducted in the penta-refractory patient population and no agents have shown activity in these patients. In light of this unmet medical need, the Company believes that positive data in this patient population could support accelerated approval.  The FDA has stated to the Company that other therapies in MM may receive full approval prior to the potential action date on any accelerated approval request for selinexor that the Company may submit, which may prevent accelerated approval for selinexor if the FDA deems that such therapies constitute earlier lines of therapy in MM that were not administered to patients in the STORM study.  Also, while the FDA has previously indicated its preference for studies that isolate the effects of individual drugs, steroids like dexamethasone are part of nearly every myeloma treatment regimen, and low-dose dexamethasone is not a single-agent treatment for MM. Other available therapies for MM, such as pomalidomide (Pomalyst®), have received accelerated approval based on studies that were conducted in combination with dexamethasone or a similar steroid. Based on these factors, the Company believes that the STORM study design and the planned expansion in the penta-refractory patient group present an opportunity for the Company to request that the FDA grant accelerated approval if data from the expansion confirm the data presented today.
  • The Company also plans to initiate a pivotal randomized Phase 3 study, known as the BOSTON (Bortezomib, Selinexor and dexamethasone) study, which will evaluate selinexor in combination with bortezomib (Velcade®) and low-dose dexamethasone (SVd) compared to bortezomib and low-dose dexamethasone (Vd) in patients with MM who have had one to three prior lines of therapy.  Based on data from the Phase 1b portion of the STOMP study, which was most recently presented at the 2016 European Hematology Association Annual Meeting, the Company has identified the combination dose to be used in the BOSTON study. Karyopharm expects that the study will enroll approximately 360 patients.  The Company intends to seek additional FDA input on the protocol for the BOSTON study prior to commencing the trial in early 2017.
  • Based in part on its plans to conduct the pivotal randomized BOSTON study to support full regulatory approval of selinexor for patients with previously-treated MM and the Company’s planned expansion of STORM to support potential accelerated approval, Karyopharm will not pursue the SCORE study at this time.  The SCORE study was designed to assess the combination of selinexor with carfilzomib (Kyprolis®) and low-dose dexamethasone.  The ongoing Phase 1/2 investigator sponsored study evaluating selinexor in combination with carfilzomib and dexamethasone in refractory MM, including carfilzomib-refractory MM, continues to enroll patients, and updated data from this study is expected to be presented later this year.

“Our updated clinical development plan for selinexor in myeloma reflects the strong foundation of clinical data from both the STORM and STOMP studies,” said Michael G. Kauffman, MD, PhD, Chief Executive Officer of Karyopharm. Dr. Kauffman was instrumental in the clinical development and regulatory approvals of Velcade® and Kyprolis® in MM. “We believe this development plan provides a path to potential FDA and EMA filings for oral selinexor in MM, with the potential to support accelerated or conditional approval if the FDA or EMA, respectively, agree. We look forward to sharing the additional data from both STORM and STOMP later this year. We believe selinexor has the potential to be a much-needed oral treatment option for patients suffering with this incurable disease.” (Original Source)

Shares of Karyopharm are up nearly 12% to $11.92 in pre-market trading. KPTI has a 1-year high of $19.41 and a 1-year low of $4.83. The stock’s 50-day moving average is $7.56 and its 200-day moving average is $8.05.

On the ratings front, Karyopharm has been the subject of a number of recent research reports. In a report issued on August 30, Jefferies analyst Brian Abrahams upgraded KPTI to Buy, with a price target of $12, which represents a potential upside of 13% from where the stock is currently trading. Separately, on August 18, H.C. Wainwright’s Shaunak Deepak initiated coverage with a Buy rating on the stock and has a price target of $15.

According to TipRanks.com, which ranks over 7,500 financial analysts and bloggers to gauge the performance of their past recommendations, Brian Abrahams and Shaunak Deepak have a total average return of 5.3% and -25.3% respectively. Abrahams has a success rate of 55% and is ranked #550 out of 4147 analysts, while Deepak has a success rate of 35% and is ranked #3936.

Overall, 5 research analysts have given a Buy rating to the stock. When considering if perhaps the stock is under or overvalued, the average price target is $12.00 which is 13.0% above where the stock closed last Friday.

Karyopharm Therapeutics, Inc. is a clinical-stage pharmaceutical company. It is focused on the discovery and development of novel first-in-class drugs directed against nuclear transport targets for the treatment of cancer and other major diseases. Its selective inhibitors of nuclear export compounds function by preventing the export of tumor suppressor proteins from the nucleus of a cell.