BOSTON, MA, USA I September 24, 2018 I Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), focused on developing and commercializing medicines to improve the survival and quality of life of cancer patients, today announced that the U.S. Food and Drug Administration (FDA) has approved COPIKTRA™, an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma. COPIKTRA is approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies.
COPIKTRA also received accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. The indication in FL is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
“With today’s FDA approval of COPIKTRA, Verastem Oncology is delivering upon our commitment to patients with cancer by bringing a new oral medicine to market,” said Robert Forrester, President and Chief Executive Officer of Verastem Oncology. “We are pleased to be able to introduce COPIKTRA during National Blood Cancer Awareness Month. At Verastem Oncology, we are driven by the strength and courage of those battling cancer, and we are committed to advancing therapies such as COPIKTRA with the potential to make a significant impact for patients, their caregivers and physicians. We are immensely grateful to the many patients who participated in the duvelisib clinical trial program over the years leading to this pivotal moment.”
“COPIKTRA is an important addition to the evolving treatment paradigm for patients with CLL/SLL and FL,” said Ian Flinn, MD, PhD, Director of the Lymphoma Research Program at Sarah Cannon Research Institute and lead investigator of the DYNAMO™ and DUO™ studies. “The approval of COPIKTRA for the treatment of relapsed or refractory CLL/SLL after at least two prior therapies, or relapsed or refractory FL after at least two prior systemic therapies, is based on clinical trial data gathered from the treatment of over 400 adult patients. COPIKTRA is a significant addition to physicians’ treatment armamentarium that I believe will address an unmet need for patients who have limited options once they have progressed after two prior therapies.”
Use of COPIKTRA is associated with a BOXED WARNING for four fatal and/or serious toxicities: infections, diarrhea or colitis, cutaneous reactions, and pneumonitis. Verastem Oncology is implementing an informational Risk Evaluation and Mitigation Strategy to provide appropriate dosing and safety information to better support physicians in managing their patients on COPIKTRA.
Additionally, use of COPIKTRA is also associated with adverse reactions which may require dose reduction, treatment delay or discontinuation of COPIKTRA. WARNINGS AND PRECAUTIONS are provided for infections, diarrhea or colitis, cutaneous reactions, pneumonitis, hepatotoxicity, neutropenia, and embryo-fetal toxicity. The most common ADVERSE REACTIONS (reported in ≥ 20% of patients) were diarrhea or colitis, neutropenia, rash, fatigue, pyrexia, cough, nausea, upper respiratory infection, pneumonia, musculoskeletal pain, and anemia.
Please see www.COPIKTRAHCP.com/prescribinginformation for full Prescribing Information including BOXED WARNING and Medication Guide in addition to the full Important Safety Information provided below.
Lymphoma is the most common blood cancer, and CLL/SLL and FL are common types of indolent non-Hodgkin lymphomas (iNHL). There are an estimated 681,000 people living with non-Hodgkin lymphoma in the US alone, including nearly 350,000 cases of CLL/SLL or FL.1 Many of these patients will eventually relapse or develop refractory disease.
“Patients living with CLL/SLL or FL are in need of additional treatment options, and new therapies such as COPIKTRA are crucial because each patient’s treatment journey is unique,” said Meghan Gutierrez, Chief Executive Officer of the Lymphoma Research Foundation. “We appreciate the commitment from companies like Verastem Oncology that research and develop these therapies with the goal of reaching a day when lymphoma is managed as a chronic disease – and eventually cured.”
The New Drug Application for COPIKTRA received Priority Review. Priority Review is reserved for medicines that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications. The FDA had previously granted COPIKTRA Fast Track Designation in CLL and FL as well as Orphan Drug Designation for CLL/SLL and FL. For the indication of FL, COPIKTRA was approved under FDA regulations for accelerated approval.
“We are excited to offer a new treatment that can allow patients to manage their disease with an oral monotherapy,” said Joseph Lobacki, Executive Vice President and Chief Commercial Officer of Verastem Oncology. “We continue to hear from physicians and patients that there is a great need for additional treatment options to fight chronic cancers such as CLL/SLL and FL. In preparation for this approval, we have assembled an experienced oncology commercial team, established our distribution network, and we are ready to make COPIKTRA commercially available to patients.”
COPIKTRA will be available in the U.S. market immediately. Verastem Oncology is committed to helping patients with CLL/SLL and FL access COPIKTRA through our Verastem Cares™ program. Verastem Cares is a comprehensive, personalized program designed to provide information and assistance to patients who have been prescribed COPIKTRA.
Patients, physicians, pharmacists, or other healthcare professionals with questions about COPIKTRA should contact 1-833-570-2273 (CARE) or visit www.COPIKTRA.com.
Conference Call Information
The Verastem Oncology management team will host a conference call today, Monday, September 24, 2018, at 4:30 PM (ET). The call can be accessed by dialing 1-877-341-5660 (toll-free) or 1-315-625-3226 (international) five minutes prior to the start of the call and providing the passcode 4496677.
The live, listen-only webcast of the conference call can be accessed by visiting the investors section of the Company’s website at www.verastem.com. A replay of the webcast will be archived on the Company’s website for 90 days following the call.
Indications and Usage
Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory CLL or SLL after at least two prior therapies.
Follicular Lymphoma (FL)*
COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory FL after at least two prior systemic therapies.
*This indication is approved under accelerated approval based on overall response rate (ORR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
COPIKTRA Clinical Trials
Efficacy in Relapsed or Refractory CLL/SLL
A randomized, multicenter, open-label trial (DUO™; NCT02004522) compared COPIKTRA versus ofatumumab in 319 adult patients with CLL (N = 312) or SLL (N = 7) after at least one prior therapy. The study randomized patients with a 1:1 ratio to receive either COPIKTRA 25mg BID until disease progression or unacceptable toxicity, or ofatumumab for 7 cycles.
The approval of COPIKTRA was based on efficacy and safety analysis of patients with at least 2 prior lines of therapy, where the benefit:risk appeared greater in this more heavily pretreated population compared to the overall trial population.
In this subset (95 randomized to COPIKTRA, 101 to ofatumumab), the median patient age was 69 years (range: 40 to 90 years), 59% were male, and 88% had an ECOG performance status of 0 or 1. Forty-six percent received 2 prior lines of therapy, and 54% received 3 or more prior lines. At baseline, 52% of patients had at least one tumor ≥ 5 cm, and 22% of patients had a documented 17p deletion.
During randomized treatment, the median duration of exposure to COPIKTRA was 13 months (range: 0.2 to 37), with 80% of patients receiving at least 6 months and 52% receiving at least 12 months of COPIKTRA. The median duration of exposure to ofatumumab was 5 months (range: < 0.1 to 6).
Efficacy was based on progression-free survival (PFS) as assessed by an Independent Review Committee (IRC). Other efficacy measures included overall response rate (ORR). Efficacy of COPIKTRA compared to ofatumumab specifically in patients treated with at least two prior therapies is below.
| Outcome per IRC |
COPIKTRA N = 95 |
Ofatumumab N = 101 |
||||
| PFS | ||||||
| Number of events, n (%) | 55 (58) | 70 (69) | ||||
| Progressive disease | 44 | 62 | ||||
| Death | 11 | 8 | ||||
| Median PFS (SE), months a | 16.4 (2.1) | 9.1 (0.5) | ||||
|
Hazard Ratio (SE), b COPIKTRA/ofatumumab |
0.40 (0.2) | |||||
| Response rate | ||||||
| ORR, n (%) c | 74 (78) | 39 (39) | ||||
| CR | 0 (0) | 0 (0) | ||||
| PR | 74 (78) | 39 (39) | ||||
| Difference in ORR, % (SE) | 39 (6.4) | |||||
Abbreviations: CR = complete response; IRC = Independent Review Committee; PFS = progression-free survival; PR = partial response; SE = standard error
a Kaplan-Meier estimate
b Standard Error of ln(hazard ratio) = 0.2
c IWCLL or revised IWG response criteria, with modification for treatment-related lymphocytosis
Efficacy in Relapsed or Refractory FL
Efficacy of COPIKTRA in patients with previously treated FL is based on a single-arm, multicenter trial (DYNAMO™; NCT01882803).
In DYNAMO, COPIKTRA 25 mg BID was administered in patients with FL (N = 83) who were refractory to rituximab and to either chemotherapy or radioimmunotherapy. Refractory disease was defined as less than a partial remission or relapse within 6 months after the last dose. The trial excluded patients with Grade 3b FL, large cell transformation, prior allogeneic transplant, and prior exposure to a PI3K inhibitor or to a Bruton’s tyrosine kinase inhibitor.
The median age was 64 years (range: 30 to 82 years), 68% were male, and 37% had bulky disease assessed at baseline (target lesion ≥ 5 cm). Patients had a median of 3 prior lines of therapy (range: 1 to 10), with 94% being refractory to their last therapy and 81% being refractory to 2 or more prior lines of therapy. Most patients (93%) had an ECOG performance status of 0 or 1.
The median duration of exposure to COPIKTRA was 5 months (range: 0.4 to 24), with 41% of patients receiving at least 6 months and 10% receiving at least 12 months of COPIKTRA.
Efficacy was based on overall response rate and duration of response as assessed by an IRC, as shown below.
| Endpoint |
FL N = 83 |
||
| ORR, n (%) a | 35 (42) | ||
| 95% CI | (31, 54) | ||
| CR, n (%) | 1 (1) | ||
| PR, n (%) | 34 (41) | ||
| Duration of response | |||
| Range, months | 0.0+ to 41.9+ | ||
| Patients maintaining response at 6 months, n/N (%) | 15/35 (43) | ||
| Patients maintaining response at 12 months, n/N (%) | 6/35 (17) |
Abbreviations: CI = confidence interval; CR = complete response; IRC = Independent Review Committee; ORR = overall response rate; PR = partial response
a Per IRC according to Revised International Working Group criteria
+ Denotes censored observation
About Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are cancers that affect lymphocytes and are essentially the same disease, with the only difference being the location where the cancer primarily occurs. When most of the cancer cells are located in the bloodstream and the bone marrow, the disease is referred to as CLL, although the lymph nodes and spleen are often involved. When the cancer cells are located mostly in the lymph nodes, the disease is called SLL. The symptoms of CLL/SLL include a tender, swollen abdomen and feeling full even after eating only a small amount. Other symptoms can include fatigue, shortness of breath, anemia, bruising easily, night sweats, weight loss, and frequent infections. However, many patients with CLL/SLL will live for years without symptoms. There are approximately 200,000 patients in the US affected by CLL/SLL with nearly 20,000 new diagnoses this year alone. While there are therapies currently available, real-world data reveals that a significant number of patients either relapse following treatment, become refractory to current agents, or are unable to tolerate treatment, representing a significant medical need. The potential of additional oral agents, particularly as a monotherapy that can be used in the general community physician’s armamentarium, may hold significant value in the treatment of patients with CLL/SLL.
About Follicular Lymphoma
Follicular lymphoma (FL) is typically a slow-growing or indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes, making it a B-cell lymphoma. This lymphoma subtype accounts for 20 to 30 percent of all NHL cases, with more than 140,000 people in the US with FL and more than 13,000 newly diagnosed patients this year. Common symptoms of FL include enlargement of the lymph nodes in the neck, underarms, abdomen, or groin, as well as fatigue, shortness of breath, night sweats, and weight loss. Often, patients with FL have no obvious symptoms of the disease at diagnosis. Follicular lymphoma is usually not considered to be curable, but more of a chronic disease, with patients living for many years with this form of lymphoma. The potential of additional oral agents, particularly as a monotherapy that can be used in the general community physician’s armamentarium, may hold significant value in the treatment of patients with FL.
About COPIKTRA™ (duvelisib)
COPIKTRA is an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells. PI3K signaling may lead to the proliferation of malignant B-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.2,3,4 COPIKTRA is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. COPIKTRA is also being developed by Verastem Oncology for the treatment of peripheral T-cell lymphoma (PTCL), for which it has received Fast Track status, and is being investigated in combination with other agents through investigator-sponsored studies.5 For more information on COPIKTRA, please visit www.COPIKTRA.com. Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.
About Verastem Oncology
Verastem, Inc. (Nasdaq:VSTM) (Verastem Oncology or the Company), is a biopharmaceutical company focused on developing and commercializing medicines to improve the survival and quality of life of cancer patients. Verastem Oncology currently markets COPIKTRA™ (duvelisib), an oral inhibitor of phosphoinositide 3-kinase (PI3K), and the first approved dual inhibitor of PI3K-delta and PI3K-gamma, which is indicated for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies and relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies. The indication in FL is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. In addition, Verastem Oncology is developing the focal adhesion kinase (FAK) inhibitor defactinib, which is currently being evaluated in three separate clinical collaborations in combination with immunotherapeutic agents for the treatment of several different cancer types, including pancreatic cancer, ovarian cancer, non-small cell lung cancer (NSCLC), and mesothelioma. Verastem Oncology’s product candidates seek to treat cancer by modulating the local tumor microenvironment and enhancing anti-tumor immunity. For more information, please visit www.verastem.com.
1 Decision Resources Group 2018 Estimates.
2 Winkler D.G., Faia K.L., DiNitto J.P. et al. PI3K-delta and PI3K-gamma inhibition by IPI-145 abrogates immune responses and suppresses activity in autoimmune and inflammatory disease models. Chem Biol 2013; 20:1-11.
3 Reif K et al. Cutting Edge: Differential Roles for Phosphoinositide 3 kinases, p110-gamma and p110-delta, in lymphocyte chemotaxis and homing. J Immunol 2004:173:2236-2240.
4 Schmid M et al. Receptor Tyrosine Kinases and TLR/IL1Rs Unexpectedly activate myeloid cell PI3K, a single convergent point promoting tumor inflammation and progression. Cancer Cell 2011;19:715-727.
5 www.clinicaltrials.gov, NCT03372057.
SOURCE: Verastem
