On February 6, 2018 Celgene Corporation (NASDAQ: CELG) reported that the Phase III, randomized, open-label, international clinical study, OPTIMISMM, achieved its primary endpoint, showing a statistically significant and clinically meaningful improvement in progression-free survival (PFS) for the pomalidomide arm versus the comparator arm (Press release, Celgene, FEB 7, 2018, View Source [SID1234523791]).

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OPTIMISMM evaluated the efficacy and safety of POMALYST/IMNOVID (pomalidomide) plus bortezomib and low-dose dexamethasone (PVd) versus bortezomib and low-dose dexamethasone in patients with relapsed/refractory multiple myeloma. It is the only phase III trial to investigate a triplet combination in patients who have all received prior lenalidomide (REVLIMID), a population for which there is a growing unmet medical need.

"The OPTIMISMM results confirm the expanding role of pomalidomide in previously treated multiple myeloma patients," said Paul Richardson, M.D., Clinical Program Leader and Director of Clinical Research, Jerome Lipper Multiple Myeloma Center at the Dana Farber Cancer Institute, RJ Corman Professor of Medicine, Harvard Medical School and principal investigator of the study. "We see the PVd combination as an important step in improving care, and especially for patients previously treated with lenalidomide in this setting."

In the study, the safety profile was consistent with previously reported data. Detailed data from OPTIMISMM will be presented at future medical meetings.

The combination of POMALYST/IMNOVID, bortezomib and low-dose dexamethasone is not currently approved for use.

About POMALYST/IMNOVID

Indication

POMALYST (pomalidomide) is a thalidomide analogue indicated, in combination with dexamethasone, for patients with multiple myeloma who have received at least two prior therapies including lenalidomide and a proteasome inhibitor and have demonstrated disease progression on or within 60 days of completion of the last therapy.

Important Safety Information

WARNING: EMBRYO-FETAL TOXICITY and VENOUS AND ARTERIAL THROMBOEMBOLISM

Embryo-Fetal Toxicity

POMALYST is contraindicated in pregnancy. POMALYST is a thalidomide analogue. Thalidomide is a known human teratogen that causes severe birth defects or embryo-fetal death. In females of reproductive potential, obtain 2 negative pregnancy tests before starting POMALYST treatment.

Females of reproductive potential must use 2 forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after stopping POMALYST treatment.

POMALYST is only available through a restricted distribution program called POMALYST REMS.

Venous and Arterial Thromboembolism

Deep venous thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke occur in patients with multiple myeloma treated with POMALYST. Prophylactic antithrombotic measures were employed in clinical trials. Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

CONTRAINDICATIONS

Pregnancy: POMALYST can cause fetal harm and is contraindicated in females who are pregnant. If POMALYST is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to a fetus.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity & Females of Reproductive Potential: See Boxed WARNINGS

Males: Pomalidomide is present in the semen of patients receiving the drug. Males must always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking POMALYST and for up to 4 weeks after discontinuing POMALYST, even if they have undergone a successful vasectomy. Males must not donate sperm.

Blood Donation: Patients must not donate blood during treatment with POMALYST and for 1 month following discontinuation of POMALYST therapy because the blood might be given to a pregnant female patient whose fetus must not be exposed to POMALYST.

POMALYST REMS Program: See Boxed WARNINGS

Prescribers and pharmacies must be certified with the POMALYST REMS program by enrolling and complying with the REMS requirements; pharmacies must only dispense to patients who are authorized to receive POMALYST. Patients must sign a Patient-Physician Agreement Form and comply with REMS requirements; female patients of reproductive potential who are not pregnant must comply with the pregnancy testing and contraception requirements and males must comply with contraception requirements.

Further information about the POMALYST REMS program is available at www.CelgeneRiskManagement.com or by telephone at 1-888-423-5436.

Venous and Arterial Thromboembolism: See Boxed WARNINGS. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient’s underlying risk factors.

Increased Mortality with Pembrolizumab: In clinical trials in patients with multiple myeloma, the addition of pembrolizumab to a thalidomide analogue plus dexamethasone resulted in increased mortality. Treatment of patients with multiple myeloma with a PD-1 or PD-L1 blocking antibody in combination with a thalidomide analogue plus dexamethasone is not recommended outside of controlled clinical trials.

Hematologic Toxicity: Neutropenia (46%) was the most frequently reported Grade 3/4 adverse reaction in patients taking POMALYST in clinical trials, followed by anemia and thrombocytopenia. Monitor complete blood counts weekly for the first 8 weeks and monthly thereafter. Patients may require dose interruption and/or modification.

Hepatotoxicity: Hepatic failure, including fatal cases, has occurred in patients treated with POMALYST. Elevated levels of alanine aminotransferase and bilirubin have also been observed in patients treated with POMALYST. Monitor liver function tests monthly. Stop POMALYST upon elevation of liver enzymes. After return to baseline values, treatment at a lower dose may be considered.

Hypersensitivity Reactions: Angioedema and severe dermatologic reactions have been reported. Discontinue POMALYST for angioedema, skin exfoliation, bullae, or any other severe dermatologic reactions, and do not resume therapy.

Dizziness and Confusional State: In patients taking POMALYST in clinical trials, 14% experienced dizziness (1% Grade 3 or 4) and 7% a confusional state (3% Grade 3 or 4). Instruct patients to avoid situations where dizziness or confusional state may be a problem and not to take other medications that may cause dizziness or confusional state without adequate medical advice.

Neuropathy: In patients taking POMALYST in clinical trials, 18% experienced neuropathy (2% Grade 3 in one trial) and 12% peripheral neuropathy.

Second Primary Malignancies: Cases of acute myelogenous leukemia have been reported in patients receiving POMALYST as an investigational therapy outside of multiple myeloma.

Tumor Lysis Syndrome (TLS): TLS may occur in patients treated with POMALYST. Patients at risk are those with high tumor burden prior to treatment. These patients should be monitored closely and appropriate precautions taken.

ADVERSE REACTIONS

Nearly all patients treated with POMALYST + low-dose dex experienced at least one adverse reaction (99%). The most common adverse reactions (≥15%) included neutropenia (51.3%), fatigue and asthenia (46.7%), upper respiratory tract infection (31%), thrombocytopenia (29.7%), pyrexia (26.7%), dyspnea (25.3%), diarrhea (22%), constipation (21.7%), back pain (19.7%), cough (20%), pneumonia (19.3%), bone pain (18%), edema peripheral (17.3%), peripheral neuropathy (17.3%), muscle spasms (15.3%), and nausea (15%). Grade 3 or 4 adverse reactions (≥15%) included neutropenia (48.3%), thrombocytopenia (22%), and pneumonia (15.7%).

DRUG INTERACTIONS

Avoid concomitant use of POMALYST with strong inhibitors of CYP1A2. Consider alternative treatments. If a strong CYP1A2 inhibitor must be used, reduce POMALYST dose by 50%.

USE IN SPECIFIC POPULATIONS

Pregnancy: See Boxed WARNINGS. If pregnancy does occur during treatment, immediately discontinue the drug and refer patient to an obstetrician/gynecologist experienced in reproductive toxicity for further evaluation and counseling. There is a POMALYST pregnancy exposure registry that monitors pregnancy outcomes in females exposed to POMALYST during pregnancy as well as female partners of male patients who are exposed to POMALYST. This registry is also used to understand the root cause for the pregnancy. Report any suspected fetal exposure to POMALYST to the FDA via the MedWatch program at 1-800-FDA-1088 and also to Celgene Corporation at 1-888-423-5436.

Lactation: There is no information regarding the presence of pomalidomide in human milk, the effects of POMALYST on the breastfed infant, or the effects of POMALYST on milk production. Pomalidomide was excreted in the milk of lactating rats. Because many drugs are excreted in human milk and because of the potential for adverse reactions in breastfed infants from POMALYST, advise a nursing woman to discontinue breastfeeding during treatment with POMALYST.

Pediatric Use: Safety and effectiveness have not been established in pediatric patients.

Geriatric Use: No dosage adjustment is required for POMALYST based on age. Patients >65 years of age were more likely than patients ≤65 years of age to experience pneumonia.

Renal Impairment: Reduce POMALYST dose by 25% in patients with severe renal impairment requiring dialysis. Take dose of POMALYST following hemodialysis on hemodialysis days.

Hepatic Impairment: Reduce POMALYST dose by 25% in patients with mild to moderate hepatic impairment and 50% in patients with severe hepatic impairment.

Smoking Tobacco: Advise patients that smoking may reduce the efficacy of POMALYST. Cigarette smoking reduces the AUC of pomalidomide by 32% by CYP1A2 induction.

On February 7, 2018 Alkermes plc (NASDAQ: ALKS) reported that it will host a conference call and webcast presentation at 8:30 a.m. ET (1:30 p.m. GMT) on Wednesday, Feb. 14, 2018, to discuss the company’s fourth quarter and year-end 2017 financial results (Press release, Alkermes, FEB 7, 2018, View Source;p=RssLanding&cat=news&id=2331037 [SID1234523789]). Management will also discuss financial expectations for 2018 and provide an update on the company.

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The webcast player and accompanying slides may be accessed on the Investors section of Alkermes’ website at www.alkermes.com. The conference call may be accessed by dialing +1 888 424 8151 for U.S. callers and +1 847 585 4422 for international callers. The conference call ID number is 6037988.

A replay of the conference call will be available from 11:00 a.m. ET (4:00 p.m. GMT) on Wednesday, Feb. 14, 2018, through 5:00 p.m. ET (10:00 p.m. GMT) on Wednesday, Feb. 21, 2018, and may be accessed by visiting Alkermes’ website or by dialing +1 888 843 7419 for U.S. callers and +1 630 652 3042 for international callers. The replay access code is 6037988.

On February 8, 2018 Atreca, Inc., a biotechnology company focused on developing novel therapeutics based on a deep understanding of the human immune response, reported that Tito A. Serafini, Ph.D., Chief Executive Officer and Co-Founder, will participate in a panel discussion on immuno—oncology being held during the 2018 BIO CEO & Investor Conference on Monday, February 12, 2018, from 9:00 AM to 10:15 AM ET in New York, NY (Press release, Atreca, FEB 7, 2018, View Source [SID1234523818]).

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The panel, titled "Immuno-Oncology Milestone’s to Come: Pipelines Beyond CAR-T 1.0", will take place at the New York Marriott Marquis.

On February 7, 2018 Exelixis, Inc. (NASDAQ:EXEL) reported updated data from expansion cohorts in a phase 1 trial of cabozantinib in combination with either nivolumab or nivolumab plus ipilimumab in patients with refractory genitourinary tumors (Press release, Exelixis, FEB 7, 2018, View Source;p=RssLanding&cat=news&id=2330900 [SID1234523782]). The primary endpoint of the trial is to determine the dose-limiting toxicity and recommended phase 2 doses of the doublet and triplet combinations. The findings will be presented during a poster session (Abstract #515) on February 9 at the 2018 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO-GU), which is being held in San Francisco, California, February 8-10, 2018.

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The updated data reported results from 78 patients treated with cabozantinib and nivolumab with or without ipilimumab. The initial part of the study determined the recommended dose for each treatment at four dose levels. In all, 49 patients were treated with the doublet combination of cabozantinib and nivolumab and 29 patients were treated with the triplet combination of cabozantinib, nivolumab and ipilimumab. Nineteen patients with mUC were evaluable for response with a median follow up of 15.7 months. Thirteen patients with previously treated mRCC were evaluable for response.

For the mUC cohort, the ORR across all treatment groups was 42 percent (2 CRs and 6 PRs of 19 patients) and the DCR (DCR = CR, PR and SD) was 84 percent. Seven of eight (88 percent) mUC patients with an objective response had not progressed at the time of the data cut-off. Median PFS in this patient population was 12.8 months and the overall survival rate at 12 months was 77 percent. Among the 13 patients with mRCC who were evaluable for response, ORR was 54 percent (7 PRs of 13 patients) and the DCR was 100 percent.

In the overall study, the ORR in 64 evaluable patients was 36 percent (3 CRs and 20 PRs) with a median duration of response (DOR) of 24 months. 78 patients were included in the safety analysis. Expected immune-related events including colitis, meningitis, hepatitis, pneumonitis and endocrine disorders occurred at a low frequency.

"The updated analysis of this trial shows that cabozantinib, in combination with nivolumab or in combination with nivolumab plus ipilimumab, demonstrates an acceptable tolerability profile and encouraging rates of durable responses in the previously treated metastatic urothelial carcinoma and metastatic renal cell carcinoma cohorts," said Andrea Apolo, M.D., Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, and principal investigator of the trial. "Evidence of clinical activity, including encouraging progression free survival in a patient population that has a significant unmet need, gives us motivation to further evaluate these combination therapies."

No dose-limiting toxicity was observed in the study. Based on general tolerability, the recommended cabozantinib dose for the expanded dose cohorts and for future late stage evaluation has been determined as cabozantinib at 40 mg daily oral dose combined with nivolumab at 3 mg/kg every 2 weeks and ipilimumab at 1 mg/kg every 3 weeks for 4 doses.

Treatment-related grade 3 or 4 adverse events (>5 percent of patients) observed in the doublet combination included lipase increased (16 percent), hypophosphatemia (14 percent), neutrophil count decreased (12 percent), hypertension (8 percent), fatigue (6 percent) and infection (6 percent). Grade 3 or 4 adverse events (>5 percent of patients) observed in the triplet combination included hypophosphatemia (21 percent), lymphocyte count decreased (14 percent), lipase increased (14 percent), ALT increased (10 percent), AST increased (10 percent), hypertension (10 percent), diarrhea (10 percent), hypokalemia (10 percent), fatigue (7 percent), hyponatremia (7 percent) and amylase increased (7 percent). Grade 3 or 4 immune-related adverse events for the doublet combination included colitis, aseptic meningitis and hepatitis (one patient each) and for the triplet combination were colitis (one patient) and hepatitis (two patients). There were no treatment-related deaths.

"We greatly value our collaboration with NCI-CTEP on this study, which suggests that the combination of cabozantinib with immune checkpoint inhibitors may have the potential to improve outcomes for patients with genitourinary malignancies, including urothelial and renal cell carcinoma," said Gisela Schwab, M.D., President, Product Development and Medical Affairs and Chief Medical Officer, Exelixis. "These phase 1 results have informed the current phase 3 trial of such combination therapy in previously untreated advanced or metastatic renal cell carcinoma, as well as future studies exploring these combinations across a range of advanced genitourinary cancers including urothelial cancer."

About the Trial

The trial is sponsored by the U.S. National Cancer Institute (NCI) through Cooperative Research and Development Agreements between the NCI’s Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment and Diagnosis, and both Bristol-Myers Squibb and Exelixis. Andrea Apolo, M.D., of the NCI’s Genitourinary Malignancies Branch, is the principal investigator. The trial is being conducted by the NCI and includes centers from its Experimental Therapeutics Clinical Trials Network.

The updated data report on findings from 78 patients with previously treated genitourinary malignancies. Forty-nine patients were treated with the doublet combination of cabozantinib and nivolumab at four dose levels and 29 patients were treated with the triplet combination of cabozantinib, nivolumab and ipilimumab at four dose levels.

The primary endpoint of the phase 1 trial is to determine the dose-limiting toxicity and recommended doses of the doublet and triplet combinations for later stage clinical studies. The secondary endpoint is clinical response rate as assessed by RECIST 1.1. The initial part of the study included four dosing levels: cabozantinib 40 mg daily plus nivolumab 1 mg/kg once every 2 weeks; cabozantinib 40 mg daily plus nivolumab 3 mg/kg once every 2 weeks; cabozantinib 60 mg daily plus nivolumab 1 mg/kg once every 2 weeks; and cabozantinib 60 mg daily plus nivolumab 3 mg/kg once every 2 weeks.

The study also included an additional four dosing levels: cabozantinib 40 mg daily, nivolumab 1 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 1 mg/kg every 2 weeks; cabozantinib 40 mg daily, nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 3 mg/kg every 2 weeks; cabozantinib 60 mg daily, nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for 4 doses, then nivolumab 3 mg/kg every 2 weeks; and cabozantinib 40 mg daily, nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for 4 doses, then nivolumab 1 mg/kg every 2 weeks.

Data from the study evaluating the combination of cabozantinib with nivolumab with or without ipilimumab in patients with previously treated genitourinary tumors were previously presented by Dr. Apolo at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2017 Congress in Madrid.

About Genitourinary Cancers

Genitourinary cancers are those that affect the urinary tract, bladder, kidneys, ureter, prostate, testicles, penis or adrenal glands — parts of the body involved in reproduction and excretion — and include renal cell carcinoma (RCC) and urothelial carcinoma.1

The American Cancer Society’s 2018 statistics cite kidney cancer as among the top ten most commonly diagnosed forms of cancer among both men and women in the U.S.2 Clear cell RCC is the most common type of kidney cancer in adults.3 If detected in its early stages, the five-year survival rate for RCC is high; for patients with advanced or late-stage metastatic RCC, however, the five-year survival rate is only 12 percent, with no identified cure for the disease.4 Approximately 30,000 patients in the U.S. and 70,000 globally require treatment.5

Urothelial cancers encompass carcinomas of the bladder, ureter and renal pelvis at a ratio of 50:3:1, respectively.6 Urothelial carcinoma occurs mainly in older people; 90 percent of patients with bladder cancer are 55 years or older.7 Bladder cancer is the fourth most common cancer in men and accounts for about five percent of all new cases of cancer in the U.S. each year.7,8 In 2014, an estimated 696,440 people were living with bladder cancer in the U.S.8

About CABOMETYX (cabozantinib)

CABOMETYX tablets are approved in the United States for the treatment of patients with advanced RCC. CABOMETYX tablets are also approved in the European Union, Norway, Iceland, Australia and Switzerland for the treatment of advanced RCC in adults who have received prior vascular endothelial growth factor (VEGF)-targeted therapy. Ipsen also submitted to European Medicines Agency (EMA) the regulatory dossier for cabozantinib as a treatment for first-line advanced RCC in the European Union on August 28, 2017; on September 8, 2017, Ipsen announced that the EMA validated the application. In 2016, Exelixis granted Ipsen exclusive rights for the commercialization and further clinical development of cabozantinib outside of the United States and Japan. In 2017, Exelixis granted exclusive rights to Takeda Pharmaceutical Company Limited for the commercialization and further clinical development of cabozantinib for all future indications in Japan, including RCC.

CABOMETYX is not indicated for the treatment of refractory mUC and other genitourinary tumors.

Please see Important Safety Information below and full U.S. prescribing information at View Source

U.S. Important Safety Information

Hemorrhage: Severe and fatal hemorrhages have occurred with CABOMETYX. In two RCC studies, the incidence of Grade ≥ 3 hemorrhagic events was 3% in CABOMETYX-treated patients. Do not administer CABOMETYX to patients that have or are at risk for severe hemorrhage.
Gastrointestinal (GI) Perforations and Fistulas: In RCC studies, fistulas were reported in 1% of CABOMETYX-treated patients. Fatal perforations occurred in patients treated with CABOMETYX. In RCC studies, gastrointestinal (GI) perforations were reported in 1% of CABOMETYX-treated patients. Monitor patients for symptoms of fistulas and perforations, including abscess and sepsis. Discontinue CABOMETYX in patients who experience a fistula which cannot be appropriately managed or a GI perforation.
Thrombotic Events: CABOMETYX treatment results in an increased incidence of thrombotic events. In RCC studies, venous thromboembolism occurred in 9% (including 5% pulmonary embolism) and arterial thromboembolism occurred in 1% of CABOMETYX-treated patients. Fatal thrombotic events occurred in the cabozantinib clinical program. Discontinue CABOMETYX in patients who develop an acute myocardial infarction or any other arterial thromboembolic complication.
Hypertension and Hypertensive Crisis: CABOMETYX treatment results in an increased incidence of treatment-emergent hypertension, including hypertensive crisis. In RCC studies, hypertension was reported in 44% (18% Grade ≥ 3) of CABOMETYX-treated patients. Monitor blood pressure prior to initiation and regularly during CABOMETYX treatment. Withhold CABOMETYX for hypertension that is not adequately controlled with medical management; when controlled, resume CABOMETYX at a reduced dose. Discontinue CABOMETYX for severe hypertension that cannot be controlled with anti-hypertensive therapy. Discontinue CABOMETYX if there is evidence of hypertensive crisis or severe hypertension despite optimal medical management.
Diarrhea: In RCC studies, diarrhea occurred in 74% of patients treated with CABOMETYX. Grade 3 diarrhea occurred in 11% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 diarrhea or Grade 3-4 diarrhea that cannot be managed with standard antidiarrheal treatments until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Palmar-Plantar Erythrodysesthesia (PPE): In RCC studies, palmar-plantar erythrodysesthesia (PPE) occurred in 42% of patients treated with CABOMETYX. Grade 3 PPE occurred in 8% of patients treated with CABOMETYX. Withhold CABOMETYX in patients who develop intolerable Grade 2 PPE or Grade 3 PPE until improvement to Grade 1; resume CABOMETYX at a reduced dose.
Reversible Posterior Leukoencephalopathy Syndrome (RPLS), a syndrome of subcortical vasogenic edema diagnosed by characteristic finding on MRI, occurred in the cabozantinib clinical program. Perform an evaluation for RPLS in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Discontinue CABOMETYX in patients who develop RPLS.
Embryo-fetal Toxicity may be associated with CABOMETYX. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during CABOMETYX treatment and for 4 months after the last dose.
Adverse Reactions: The most commonly reported (≥25%) adverse reactions are: diarrhea, fatigue, nausea, decreased appetite, hypertension, PPE, weight decreased, vomiting, dysgeusia, and stomatitis.
Strong CYP3A4 Inhibitors: If concomitant use with strong CYP3A4 inhibitors cannot be avoided, reduce the CABOMETYX dosage.
Strong CYP3A4 Inducers: If concomitant use with strong CYP3A4 inducers cannot be avoided, increase the CABOMETYX dosage.
Lactation: Advise women not to breastfeed while taking CABOMETYX and for 4 months after the final dose.
Hepatic Impairment: In patients with mild to moderate hepatic impairment, reduce the CABOMETYX dosage.

CABOMETYX is not recommended for use in patients with severe hepatic impairment.
Please see accompanying full Prescribing Information View Source

On February 7, 2018 Verastem, Inc. (NASDAQ: VSTM), focused on discovering and developing drugs to improve the survival and quality of life of cancer patients, reported it has submitted a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) seeking full approval for its lead product candidate duvelisib, a first-in-class oral dual inhibitor of phosphoinositide-3-kinase (PI3K)-delta and PI3K-gamma, for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed or refractory follicular lymphoma (FL) (Press release, Verastem, FEB 7, 2018, View Source;p=RssLanding&cat=news&id=2330853 [SID1234523775]). Duvelisib has received Fast Track Designation from the FDA for patients with CLL or peripheral T-cell lymphoma (PTCL) who have received at least one prior therapy and for patients with FL who have received at least two prior therapies. In addition, duvelisib received orphan drug designation in the United States and the European Union for patients with CLL, SLL and FL.

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"The submission of our first NDA for duvelisib is a major milestone for Verastem and is the culmination of substantial effort by our employees and the investigators who have dedicated themselves toward developing a potential treatment option for patients who are in need of additional therapies. We are immensely grateful to all of the patients that participated in the duvelisib clinical trial program over the last few years," said Robert Forrester, President and Chief Executive Officer of Verastem. "Oral duvelisib is the first PI3K inhibitor to show efficacy as a monotherapy in a randomized Phase 3 study in patients with relapsed or refractory CLL/SLL. Duvelisib monotherapy has also demonstrated significant clinical activity in patients with double-refractory FL. We believe duvelisib will offer a convenient oral treatment alternative. We look forward to working with the FDA during the review process and to a potential U.S. approval decision for duvelisib in early 2019."

The NDA is supported by clinical data from the randomized Phase 3 DUO study demonstrating significant efficacy, along with a consistent and manageable safety profile, of duvelisib monotherapy in patients with relapsed or refractory CLL/SLL. The DUO study met its primary endpoint with oral duvelisib monotherapy achieving a statistically significant improvement in progression-free survival (PFS) compared to ofatumumab in patients with relapsed or refractory CLL/ SLL (median PFS of 13.3 months versus 9.9 months, respectively; HR=0.52; p<0.0001), representing a 48% reduction in the risk of disease progression or death. The NDA is also supported by results from the Phase 2 DYNAMO study in patients with indolent non-Hodgkin’s lymphoma that are double-refractory to both rituximab and chemotherapy or radioimmunotherapy, which also achieved its primary endpoint with an objective response rate (ORR) of 46% (p<0.0001). In the subset of patients enrolled in DYNAMO with double-refractory FL (n=83), duvelisib demonstrated an ORR of 41%.

About Duvelisib

Duvelisib is a first-in-class investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib was evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints and Verastem has submitted a New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL). Duvelisib is also being developed by Verastem for the treatment of peripheral T-cell lymphoma (PTCL), and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.