On December 12, 2017 Actinium Pharmaceuticals, Inc. (NYSE American:ATNM) ("Actinium" or "the Company"), reported data at the 59th Annual American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition on the labeling of daratumumab, a CD38 targeting antibody which is marketed commercially by Johnson and Johnson (JNJ) under the trade name Darzalex, with the radioisotope Actinium-225 (Press release, Actinium Pharmaceuticals, DEC 12, 2017, View Source [SID1234522567]). The ARC or Antibody Radio-Conjugate of daratumumab labeled with the radioisotope Actinium-225 demonstrated enhanced targeted cancer cell killing in vitro compared with naked daratumumab. Actinium is a clinical-stage biopharmaceutical company focused on developing and commercializing targeted therapies for safer myeloablation and conditioning of the bone marrow prior to a bone marrow transplant, and for the targeting and killing of cancer cells, This initiative comes from Actinium’s AWE or Actinium Warhead Enabling Technology Platform that combines the isotope Actinium-225 with monoclonal antibodies to create ARC’s.

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The poster highlighted the capabilities of the Company’s recently announced AWE or Actinium Warhead Enabling Program that studied the effect of Actinium-225 labeled daratumumab on DAUDI, 28BM and 28PE cell lines at the 48, 72 and 96 hour time points as well as U226, a cell line that does not express CD38. The results showed that when daratumuamb is labeled with Actinium-225, cell death was increased as much as ten-fold, approaching one-hundred percent cell death in certain cell lines and at certain time points, and in all three cell lines tested the Actinium-225 labeled daratumumab had higher cell death compared to naked daratumumab. In addition, immunogenicity was preserved with most or all of daratumumab’s CD38 targeting ability maintained, high rates of radioisotope labeling of the antibody from 82-85% was demonstrated, as was high rates of stability from 73-87% at various temperatures forty-eight hours post labeling. As a result of this promising data, Actinium is continuing to investigate Actinium-225 labeled daratumumab further, with in vivo experiments ongoing.

The abstract for the poster can be accessed through the following link: View Source

Dr. Mark Berger, Actinium’s Chief Medical Officer said, "These promising results showcase the power of our AWE Technology Platform. The ability to increase the cell killing power of an antibody while preserving its targeting ability is a powerful premise that can have profound impacts on the treatment of patients and outcomes. Given these initial positive results we look forward to continuing to expand our AWE Program by labeling additional antibodies, and even other targeting moeities, with Actinium-225 to fully leverage the targeted potency of Actinium-225, our proprietary technology, and our team’s expertise and know how."

Daratumumab (Darzalexâ, Janssen) is an immunoglobulin G1 kappa (IgG1к) cytolytic human monoclonal antibody directed against the CD38 antigen that is approved to treat patients with multiple myeloma. First approved in 2015 as a monotherapy for patients who have received three prior therapies, daratumumab is now approved for use in combination and has also received approvals in earlier lines of treatment and has achieved blockbuster sales in excess of one billion dollars in the last twelve months. Daramtumumab’s effective targeting of the CD38 antigen and its success in the clinical setting indicates a high efficacy baseline, making it an ideal candidate antibody for which to demonstrate additional benefits in efficacy as a result of Actinium-225 enablement. While daratumumab is increasingly being used to treat patients, infusion reactions are common, likely due in part to administration of a large dose at 16 mg/kg, which requires long infusion times. Additionally, the infusions must take place frequently – weekly for the first 8 weeks, followed by bi-weekly infusions up to week 25, after which monthly infusions are required.

Sandesh Seth, Actinium’s Chairman and CEO added, "There has been a renaissance in radioisotope based therapies of late while antibodies continue to prove to be beneficial therapies for patients in numerous oncology indications. Our AWE Technology Platform is able to combine the strengths of these modalities to create ARC’s or Antibody Radio-Conjugates that leverage the targeted potency of the actinium-225 isotope and our proprietary technology. With this detailed data now available, we look forward to showcasing this capability to potential partners and collaborators as an example of the value generating potential of our AWE Program. We are confident that enhanced cell killing power via Actinium-225 will be attractive to developers of both novel and approved antibodies as a means to generate pipeline opportunities via de novo efforts and life cycle management. We look forward to actively promoting our AWE program in 2018 based on the 2017 enhancements in technology, scientific capabilities and team at Actinium."

About Our Actinium Warhead Enabling Technology Platform

The Actinium Warhead Enabling (AWE) Technology Platform enables a highly potent and selective form of targeted therapy that combines the powerful alpha-emitting radioisotope actinium-225 with targeting agents, which are designed to seek out cancer cells in the body that express particular markers. Actinium-225 emits significant alpha radiation making it a potent treatment modality against targeted cancer cells while limiting damage to healthy tissues as its radiation travels extremely short distances in the body. When labeled to targeting agents, actinium-225 can be delivered directly to cancer cells where the high linear energy transfer resulting from the emission of alpha particles results in irreparable DNA double stranded breaks and ultimately cancer cell death. Despite this superior cell killing power, actinium-225 when delivered in a targeted manner is sparing of the surrounding environment in the body due to the short path length of its alpha-particle radiation and can result in a superior safety profile. Actinium Pharmaceuticals owns or has licensed the rights to several issued and pending patents that pertain to its AWE Technology Platform including technology to manufacture Actinium-225 in a cyclotron. In addition, the Company obtains actinium-225 from various sources such as the U.S. Department of Energy at Oak Ridge National Laboratories and has developed considerable know-how, expertise and validated processes related to production of antibody radio-conjugates (ARC), management of the supply chain and dealing with various regulatory bodies. The AWE Technology Platform can be utilized to potentially improve the cell-killing power of targeting agents such as antibodies, peptides, Fab fragments, nanobodies etc. via labeling with Actinium-225. In addition to increased efficacy, these Actinium-225 enhanced targeting agents can offer optimized dosing or administration and in the case of approved targeting agents provide an opportunity to extend intellectual property protection by the creation of biobetters or improved versions of the approved agent. The Company’s Actinium Warhead Enabling (AWE) Program can be accessed by biopharmaceutical companies that are interested in creating biobetters through the utilization of the AWE Platform Technology. To learn more about the AWE Technology Platform or the AWE Program please contact Keisha Thomas, Ph.D., Corporate Development at [email protected].

On December 12, 2017 TapImmune Inc. (NASDAQ: TPIV), a leading clinical-stage immuno-oncology company with ongoing clinical trials in ovarian and breast cancer, reported that the first patient has been enrolled in a Phase 2 randomized, multi-center, double-blinded, placebo-controlled clinical trial of TapImmune’s novel therapeutic vaccine candidate TPIV200 (Press release, TapImmune, DEC 12, 2017, View Source [SID1234523779]). The 280-patient trial, sponsored by Mayo Clinic, received $13.3 million in grant funding from the U.S. Department of Defense (DoD) to evaluate the prevention of cancer recurrence in women with triple-negative breast cancer (TNBC) who have completed first-line surgery and radiotherapy/chemotherapy.

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TPIV200 is a novel, multi-epitope, peptide-based cancer vaccine that has been shown to induce a robust and long-lasting "memory" T-cell immune response directed against folate receptor alpha (FRa), a molecule that is overexpressed on the surface of the vast majority of TNBC cancer cells and is associated with cancer recurrence. As an off-the-shelf vaccine consisting of several carefully chosen FRa peptides, TPIV200 is uniquely able to stimulate both T "helper" cells and T "killer" cells to target tumor cells and is expected to cover greater than 85% of human genotypes worldwide.

"We remain grateful to the U.S. Department of Defense and Mayo Clinic for enabling TapImmune to gain invaluable clinical safety and efficacy insight for TPIV200 under this grant," said TapImmune President and CEO Peter Hoang. "We believe TPIV200 and our other vaccine candidates have an important role to play within the current immuno-oncology ecosystem by potentially bridging a critical gap not currently addressed by other immunotherapies, which have shown promise in only a small number of patients. Unlike current approaches, TapImmune’s vaccines are designed to produce broad-based, durable T-cell responses in the vast majority of patients, which we believe are essential for improving clinical outcomes and ensuring potential regulatory and commercial success. We look forward to providing updates appropriately as this exciting Phase 2 study continues to enroll patients."

TapImmune and its clinical partners are evaluating TPIV200 in multiple ongoing Phase 2 trials for treating ovarian and breast cancer, including a randomized dosing trial in TNBC that recently completed patient enrollment. The four-arm trial is designed to help determine the optimal TPIV200 vaccine dose and regimen to maximize patients’ anti-tumor immune responses. Interim immunogenicity results from this ongoing study are anticipated in the first half of 2018.

Keith L. Knutson. Ph.D., Professor of Immunology in the Department of Immunology, and Edith A. Perez, M.D., Professor of Medicine in the Division of Hematology and Oncology, both at Mayo Clinic’s Florida campus in Jacksonville, Florida, are the recipients of the U.S. Department of Defense grant and are leading the Phase 2 trial.

Mayo Clinic and Dr. Knutson have a financial interest in TapImmune for the triple negative breast cancer treatment.

On December 12, 2017 Innovation Pharmaceuticals, (OTCQB:IPIX) ("the Company"), a clinical stage biopharmaceutical company, reported that the European Patent Office has granted a European patent for Brilacidin, the Company’s first-in-class defensin-mimetic, in the prevention and control of Oral Mucositis (OM) (Press release, Innovation Pharmaceuticals, DEC 12, 2017, View Source [SID1234522572]). Brilacidin-OM is being developed under an FDA Fast Track designation for this indication.

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The European patent supplements other Brilacidin-OM patents that have been granted in the United States, Asia (Japan, Taiwan, China), Oceania (Australia) and South Africa. All currently issued patents have an expiration date of 2032. Additional Brilacidin-OM patent applications are pending in other key markets including Russia and South Korea.

The European patent is part and parcel to the Company’s strategy to develop and commercialize Brilacidin-OM internationally through licensing agreements. An estimated 700,000 (source: GLOBOCAN) Head and Neck Cancer (HNC) patients worldwide will develop OM this year, with the figures expected to climb to over one million annually by 2023. In spite of OM incidence rates ranging as high as 100 percent in HNC, there currently are no FDA-approved drugs for the prevention and treatment of OM in these types of cancer patients receiving chemoradiation.

"We are looking at a global product opportunity with OM that is extremely attractive and intellectual property protection is critical. With no approved drugs for our initial target indication in preventing OM in HNC, the first company to commercialize a safe and effective drug would undoubtedly command a significant portion of the market, which is estimated to be at least $1 billion worldwide," said Leo Ehrlich, Chief Executive Officer at Innovation Pharmaceuticals.

"The topline data released yesterday from our Phase 2 trial showed a meaningful reduction in the incidence of severe OM even compared to a rate somewhat lower than historic norms in the placebo arm, demonstrating Brilacidin-OM’s clear effect in preventing this extremely painful, and at times even deadly, consequence of chemoradiation in a majority of HNC patients treated with the drug. I can’t imagine a physician not wanting to prescribe, and a patient not wanting to use, a simple oral rinse like Brilacidin-OM if it would mean cutting the chance of developing severe OM by as much as 38.7 percent, as observed in patients who adhered to the requirements of the trial protocol," Mr. Ehrlich continued.

"Given the positive topline data, the Company is compelled to aggressively seek a development path that will most efficiently bring Brilacidin-OM to patients in need," said Arthur P. Bertolino, MD, PhD, MBA, President and Chief Medical Officer at Innovation Pharmaceuticals. "We intend to work diligently with the FDA and other health authorities, on a worldwide basis, and ideally in collaboration with interested potential partners, to achieve this goal. We have a potential "game changer" asset with Brilacidin-OM, able to make a big impact on a cancer patient’s well-being, and we are in the privileged position of planning wholeheartedly for the next stage of development as we strive to be the first to fill a wide void in oncology as quickly as possible."

On December 12, 2017 AbbVie (NYSE: ABBV), a research and development based global biopharmaceutical company, reported the first presentation of efficacy and safety results from MURANO, an international, multicenter, open-label, randomized Phase 3 study of VENCLEXTA/VENCLYXTO (venetoclax) in combination with Rituxan (rituximab) compared with bendamustine in combination with Rituxan in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) AbbVie (NYSE: ABBV), a research and development based global biopharmaceutical company, reported the first presentation of efficacy and safety results from MURANO, an international, multicenter, open-label, randomized Phase 3 study of VENCLEXTA/VENCLYXTO (venetoclax) in combination with Rituxan (rituximab) compared with bendamustine in combination with Rituxan in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) (Press release, AbbVie, DEC 12, 2017, View Source [SID1234522576]).

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Investigator-assessed results showed that patients with R/R CLL achieved significantly prolonged median progression-free survival (PFS) with VENCLEXTA/VENCLYXTO in combination with Rituxan [median PFS, not reached], compared with bendamustine in combination with Rituxan [median PFS, 17.0 months; hazard ratio, 0.17; 95% CI, 0.11–0.25; P<0.0001].1 Twenty-four month PFS estimates were 84.9 percent and 36.3 percent, respectively.1 Independent Review Committee (IRC)-assessed PFS showed similar results.1 Additionally, consistent improvement in PFS was observed across the patient subgroups assessed in the trial, including patients with 17p deletion [hazard ratio 0.14; 95% CI, 0.06–0.33].1 VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

At the time of the interim analysis, safety data were consistent with the known safety profiles of the medicines.1

"The data from the MURANO trial represents the next evolution in a potential treatment option for patients with relapsed/refractory CLL, an indication for which we received Breakthrough Therapy Designation," said Michael Severino, M.D., executive vice president, research and development, and chief scientific officer, AbbVie. "We are proud to present these findings at the ASH (Free ASH Whitepaper) annual meeting and are working closely with regulatory authorities to bring this combination therapy to appropriate patients as soon as possible."

The data also serves as the Phase 3 confirmatory study requested by the U.S. Food and Drug Administration (FDA) when VENCLEXTA was granted accelerated approval on April 11, 2016.2 Health authority regulatory submissions of VENCLEXTA/VENCLYXTO in combination with Rituxan are underway.

"This primary analysis of the MURANO trial showed a significant improvement in PFS with VENCLEXTA/VENCLYXTO and Rituxan versus bendamustine and Rituxan, with consistent results in all patient subsets assessed," said John Seymour, M.D., Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia and lead investigator of the MURANO trial. "Based on the efficacy and safety results of this trial, the VENCLEXTA/VENCLYXTO and Rituxan combination has the potential to offer a new chemotherapy-free regimen for patients with relapsed/refractory CLL. We continue to monitor safety and efficacy in trial patients to gain further data and information."

Design and Results of Phase 3 Study Presented at ASH (Free ASH Whitepaper)
A total of 389 patients with R/R CLL who had received one to three prior therapies were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO study.1 The study was designed to evaluate the efficacy and safety of VENCLEXTA/VENCLYXTO in combination with Rituxan (194 patients; median age, 64.5 years) compared with bendamustine in combination with Rituxan (195 patients; median age, 66.0 years).1

For patients receiving VENCLEXTA/VENCLYXTO in combination with Rituxan, a 4-week or 5-week dose ramp-up of VENCLEXTA/VENCLYXTO from 20 to 400 mg daily was used to mitigate potential tumor lysis syndrome (TLS) risk.1 Beginning at week 6, intravenous (IV) Rituxan was given monthly for six 28-day cycles (375 mg/m2 first dose, then 500 mg/m2).1 Patients continued with VENCLEXTA/VENCLYXTO 400 mg for a maximum of two years or until disease progression, whichever was first.1 For patients receiving bendamustine in combination with Rituxan, patients were given bendamustine (70 mg/m2 IV) on days 1 and 2 of each of six 28-day cycles in combination with Rituxan using the same dosing schedule.1

The primary endpoint was investigator-assessed PFS, which was determined using standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.3 Secondary endpoints included Independent Review Committee (IRC)-assessed PFS, as well as PFS in patients with 17p deletion, best overall response (defined as complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial response [nPR], or partial response [PR]), overall survival (OS), event-free survival, duration of response, time to next anti-CLL treatment, and percentage of patients achieving minimal residual disease (MRD)-negativity.3 As of May 8, 2017, median follow-up was 23.8 months (range, 0-37.4 months).1

Study Results:1

Endpoint*

Investigator-Assessed
Independent Review Committee
Progression-Free Survival
VR: 84.9%
VR: 82.8%4
(24-month estimate)
BR: 36.3%
BR: 37.4%4

Median PFS
VR: Not reached
VR: Not reached4

BR: 17.0 months
BR: 18.1 months4

HR (95% CI)
HR=0.17 (0.11–0.25)
HR=0.19 (0.13- 0.28)
P-value
P <0.0001
P <0.0001

Overall Response
VR: 93.3% (181/194)
VR: 92.3% (179/194)
(CR, CRi, PR, nPR)
BR: 67.7% (132/195)
BR: 72.3% (141/195)

Difference (95% CI)
25.6% (17.9-33.3)
20.0% (12.4-27.6)

Complete Response
VR: 26.8% (52/194)
VR: 8.2% (16/194)
(CR/CRi)
BR: 8.2% (16/195)
BR: 3.6% (7/195)

Difference (95% CI)
18.6%
4.7% (-0.3, 9.6)
P-value

P=NS

Partial Response
VR: 66.5% (129/194)
VR: 84.0% (163/194)
(PR/nPR)
BR: 59.5% (116/195)

BR: 68.7% (134/195)
Overall Survival

(OS)

Events
VR 7.7% (15/194)4

BR 13.8% (27/195)4

HR (95% CI)
HR =0.48 (0.25-0.90)4

Peripheral blood Minimal Residual Disease Negativity
VR: 83.5% (162/194)
BR: 23.1% (45/195)
(MRD-)**

Difference (95% CI)
60.4% (52.3–68.6)
*Abbreviations: VR (VENCLYXTO/VENCLEXTA+ Rituxan); BR (bendamustine + Rituxan); NS (not significant)
** Best response at any timepoint; MRD negativity was defined as less than 1 CLL cell in 10,000 leukocytes
In the study, the adverse events (AEs) were consistent with the known safety profile of VENCLEXTA/VENCLYXTO and Rituxan. Grade 3-4 neutropenia was higher in the VENCLEXTA/VENCLYXTO in combination with Rituxan arm of the trial. 1 For patients taking VENCLEXTA/VENCLYXTO in combination with Rituxan and bendamustine in combination with Rituxan, there were 6 (3.1 percent) and 2 (1.1 percent) grade ≥3 TLS AEs reported in each arm, respectively.1 For VENCLEXTA/VENCLYXTO in combination with Rituxan versus bendamustine in combination with Rituxan, respectively, Richter transformation was confirmed in 6 and 5 patients, and AEs leading to death were seen in 10 (5.2 percent) versus 11 (5.9 percent) patients.1

Summary of Adverse Events (AEs):1

Adverse Events*

Venetoclax in combination with
rituximab (N= 194)

Bendamustine in combination with
rituximab (N=195)

Number of AEs
335
255
Grade 3-4 AEs occurring in > 5
percent in either arm, n (%)
Neutropenia
Anemia
Thrombocytopenia
Febrile neutropenia
Pneumonia
Infusion-related reaction

112 (57.7)
21 (10.8)
11 (5.7)
7 (3.6)
10 (5.2)
3 (1.5)

73 (38.8)
26 (13.8)
19 (10.1)
18 (9.6)
15 (8.0)
10 (5.3)
Serious AEs in > 2 patients
in either arm, n (%)

Pneumonia
Influenza
Sepsis
Upper respiratory tract infection
Lung infection
Sinusitis
Appendicitis
Bronchitis
Pharyngitis
Respiratory tract infection

16 (8.2)
3 (1.5)
1 (0.5)
3 (1.5)
3 (1.5)
2 (1.0)
2 (1.0)
0
0
2 (1.0)

15 (8.0)
2 (1.1)
4 (2.1)
2 (1.1)
0
1 (0.5)
0
2 (1.1)
2 (1.1)
0
Fatal AEs, n (%)
10 (5.2)
11 (5.9)
*AE reporting period: up to 90 days after end of bendamustine and rituximab treatment (maximum six months); up to 28 days after end of venetoclax and rituximab treatment (maximum two years).
About VENCLEXTA/VENCLYXTO
VENCLEXTA/VENCLYXTO is an oral B-cell lymphoma-2 (BCL-2) inhibitor that targets a specific protein in the body called BCL-2.2,5 When you have CLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally.2,5 VENCLEXTA/VENCLYXTO targets BCL-2 in order to help restore the process of apoptosis.2,5 Through apoptosis, your body allows cancer cells and normal cells to self-destruct.2,5

VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in clinical trials in several hematologic cancers.

VENCLEXTA/VENCLYXTO is currently approved in 49 nations, including the U.S., and in the EU. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.

About VENCLYXTO (venetoclax) Tablets (EU)
VENCLYXTO (venetoclax) is indicated in the European Union (EU) for the treatment of chronic lymphocytic leukemia (CLL) in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.5 It is also being evaluated for the treatment of patients with various blood cancer types. 1,6,7,8,9 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.1 VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.1

Important VENCLYXTO (venetoclax) EU Safety Information
Contraindications
Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John’s wort.

Special Warnings & Precautions for Use
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS. Blood chemistries should be monitored and abnormalities managed promptly. More intensive measures (including IV hydration, frequent monitoring and hospitalization) should be employed as overall risk increases.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.

Avoid co-administration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, upper respiratory tract infection, fatigue, hyperphosphatemia, vomiting and constipation.

The most frequently occurring adverse reactions (>=2%) were pneumonia, febrile neutropenia and TLS.

Discontinuations due to adverse reactions occurred in 9.1% of patients and dosage adjustments due to adverse reactions occurred in 11.8% of patients.

Specific Populations
VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Advise nursing women to discontinue breastfeeding during treatment.

Safety in patients with severe renal impairment or on dialysis has not been established, and a recommended dose has not been determined. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk. Monitor closely for signs of toxicity due to increased risk of TLS.

This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

About VENCLEXTA (venetoclax) tablets (US)
In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval of VENCLEXTA (venetoclax) tablets for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.2 The FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

VENCLEXTA has been granted four Breakthrough Therapy Designations from the FDA including for the combination treatment of patients with untreated AML not eligible for standard induction chemotherapy. This designation is intended to expedite the development and review of therapies for serious or life-threatening conditions.10 In January 2016, AbbVie announced that the FDA granted priority review for the single agent NDA application for VENCLEXTA.

In November 2017, AbbVie and Genentech received the Prix Galien award for "Best Pharmaceutical Product" for VENCLEXTA.11

What is VENCLEXTA (venetoclax)?
VENCLEXTA (venetoclax) is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least one prior treatment.

VENCLEXTA was approved based on response rate. There is an ongoing study to find out how VENCLEXTA works over a longer period of time.

It is not known if VENCLEXTA is safe and effective in children.

Important VENCLEXTA (venetoclax) US Safety Information

What is the most important information I should know about VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your doctor will do tests for TLS. It is important to keep your appointments for blood tests. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Tell your doctor right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water when taking VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other, causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your doctor.
What should I tell my doctor before taking VENCLEXTA?
Before taking VENCLEXTA, tell your doctor about all of your medical conditions, including if you:

Have kidney or liver problems.
Have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium
Have a history of high uric acid levels in your blood or gout
Are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during or after treatment with VENCLEXTA until your doctor tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your doctor. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
Are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA.
Are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:

Low white blood cell count (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your doctor will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your doctor right away if you have a fever or any signs of an infection.
The most common side effects of VENCLEXTA include low white blood cell count, diarrhea, nausea, low red blood cell count, upper respiratory tract infection, low platelet count, and feeling tired.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your doctor if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. Tell your doctor if you have any side effect that bothers you or that does not go away.

The full U.S. prescribing information for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information.

Patient Assistance
For those who qualify, patient assistance options are available for people taking VENCLEXTA in the U.S.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. With the acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our research and development efforts, and through collaborations, AbbVie’s oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 200 clinical trials and more than 20 different tumor types. For more information, please visit View Source

.

Investigator-assessed results showed that patients with R/R CLL achieved significantly prolonged median progression-free survival (PFS) with VENCLEXTA/VENCLYXTO in combination with Rituxan [median PFS, not reached], compared with bendamustine in combination with Rituxan [median PFS, 17.0 months; hazard ratio, 0.17; 95% CI, 0.11–0.25; P<0.0001].1 Twenty-four month PFS estimates were 84.9 percent and 36.3 percent, respectively.1 Independent Review Committee (IRC)-assessed PFS showed similar results.1 Additionally, consistent improvement in PFS was observed across the patient subgroups assessed in the trial, including patients with 17p deletion [hazard ratio 0.14; 95% CI, 0.06–0.33].1 VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

At the time of the interim analysis, safety data were consistent with the known safety profiles of the medicines.1

"The data from the MURANO trial represents the next evolution in a potential treatment option for patients with relapsed/refractory CLL, an indication for which we received Breakthrough Therapy Designation," said Michael Severino, M.D., executive vice president, research and development, and chief scientific officer, AbbVie. "We are proud to present these findings at the ASH (Free ASH Whitepaper) annual meeting and are working closely with regulatory authorities to bring this combination therapy to appropriate patients as soon as possible."

The data also serves as the Phase 3 confirmatory study requested by the U.S. Food and Drug Administration (FDA) when VENCLEXTA was granted accelerated approval on April 11, 2016.2 Health authority regulatory submissions of VENCLEXTA/VENCLYXTO in combination with Rituxan are underway.

"This primary analysis of the MURANO trial showed a significant improvement in PFS with VENCLEXTA/VENCLYXTO and Rituxan versus bendamustine and Rituxan, with consistent results in all patient subsets assessed," said John Seymour, M.D., Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia and lead investigator of the MURANO trial. "Based on the efficacy and safety results of this trial, the VENCLEXTA/VENCLYXTO and Rituxan combination has the potential to offer a new chemotherapy-free regimen for patients with relapsed/refractory CLL. We continue to monitor safety and efficacy in trial patients to gain further data and information."

Design and Results of Phase 3 Study Presented at ASH (Free ASH Whitepaper)
A total of 389 patients with R/R CLL who had received one to three prior therapies were enrolled in the international, multicenter, open-label, randomized Phase 3 MURANO study.1 The study was designed to evaluate the efficacy and safety of VENCLEXTA/VENCLYXTO in combination with Rituxan (194 patients; median age, 64.5 years) compared with bendamustine in combination with Rituxan (195 patients; median age, 66.0 years).1

For patients receiving VENCLEXTA/VENCLYXTO in combination with Rituxan, a 4-week or 5-week dose ramp-up of VENCLEXTA/VENCLYXTO from 20 to 400 mg daily was used to mitigate potential tumor lysis syndrome (TLS) risk.1 Beginning at week 6, intravenous (IV) Rituxan was given monthly for six 28-day cycles (375 mg/m2 first dose, then 500 mg/m2).1 Patients continued with VENCLEXTA/VENCLYXTO 400 mg for a maximum of two years or until disease progression, whichever was first.1 For patients receiving bendamustine in combination with Rituxan, patients were given bendamustine (70 mg/m2 IV) on days 1 and 2 of each of six 28-day cycles in combination with Rituxan using the same dosing schedule.1

The primary endpoint was investigator-assessed PFS, which was determined using standard International Workshop on Chronic Lymphocytic Leukemia (iwCLL) guidelines.3 Secondary endpoints included Independent Review Committee (IRC)-assessed PFS, as well as PFS in patients with 17p deletion, best overall response (defined as complete response [CR], complete response with incomplete marrow recovery [CRi], nodular partial response [nPR], or partial response [PR]), overall survival (OS), event-free survival, duration of response, time to next anti-CLL treatment, and percentage of patients achieving minimal residual disease (MRD)-negativity.3 As of May 8, 2017, median follow-up was 23.8 months (range, 0-37.4 months).1

Study Results:1

Endpoint*

Investigator-Assessed
Independent Review Committee
Progression-Free Survival
VR: 84.9%
VR: 82.8%4
(24-month estimate)
BR: 36.3%
BR: 37.4%4

Median PFS
VR: Not reached
VR: Not reached4

BR: 17.0 months
BR: 18.1 months4

HR (95% CI)
HR=0.17 (0.11–0.25)
HR=0.19 (0.13- 0.28)
P-value
P <0.0001
P <0.0001

Overall Response
VR: 93.3% (181/194)
VR: 92.3% (179/194)
(CR, CRi, PR, nPR)
BR: 67.7% (132/195)
BR: 72.3% (141/195)

Difference (95% CI)
25.6% (17.9-33.3)
20.0% (12.4-27.6)

Complete Response
VR: 26.8% (52/194)
VR: 8.2% (16/194)
(CR/CRi)
BR: 8.2% (16/195)
BR: 3.6% (7/195)

Difference (95% CI)
18.6%
4.7% (-0.3, 9.6)
P-value

P=NS

Partial Response
VR: 66.5% (129/194)
VR: 84.0% (163/194)
(PR/nPR)
BR: 59.5% (116/195)

BR: 68.7% (134/195)
Overall Survival

(OS)

Events
VR 7.7% (15/194)4

BR 13.8% (27/195)4

HR (95% CI)
HR =0.48 (0.25-0.90)4

Peripheral blood Minimal Residual Disease Negativity
VR: 83.5% (162/194)
BR: 23.1% (45/195)
(MRD-)**

Difference (95% CI)
60.4% (52.3–68.6)
*Abbreviations: VR (VENCLYXTO/VENCLEXTA+ Rituxan); BR (bendamustine + Rituxan); NS (not significant)
** Best response at any timepoint; MRD negativity was defined as less than 1 CLL cell in 10,000 leukocytes
In the study, the adverse events (AEs) were consistent with the known safety profile of VENCLEXTA/VENCLYXTO and Rituxan. Grade 3-4 neutropenia was higher in the VENCLEXTA/VENCLYXTO in combination with Rituxan arm of the trial. 1 For patients taking VENCLEXTA/VENCLYXTO in combination with Rituxan and bendamustine in combination with Rituxan, there were 6 (3.1 percent) and 2 (1.1 percent) grade ≥3 TLS AEs reported in each arm, respectively.1 For VENCLEXTA/VENCLYXTO in combination with Rituxan versus bendamustine in combination with Rituxan, respectively, Richter transformation was confirmed in 6 and 5 patients, and AEs leading to death were seen in 10 (5.2 percent) versus 11 (5.9 percent) patients.1

Summary of Adverse Events (AEs):1

Adverse Events*

Venetoclax in combination with
rituximab (N= 194)

Bendamustine in combination with
rituximab (N=195)

Number of AEs
335
255
Grade 3-4 AEs occurring in > 5
percent in either arm, n (%)
Neutropenia
Anemia
Thrombocytopenia
Febrile neutropenia
Pneumonia
Infusion-related reaction

112 (57.7)
21 (10.8)
11 (5.7)
7 (3.6)
10 (5.2)
3 (1.5)

73 (38.8)
26 (13.8)
19 (10.1)
18 (9.6)
15 (8.0)
10 (5.3)
Serious AEs in > 2 patients
in either arm, n (%)

Pneumonia
Influenza
Sepsis
Upper respiratory tract infection
Lung infection
Sinusitis
Appendicitis
Bronchitis
Pharyngitis
Respiratory tract infection

16 (8.2)
3 (1.5)
1 (0.5)
3 (1.5)
3 (1.5)
2 (1.0)
2 (1.0)
0
0
2 (1.0)

15 (8.0)
2 (1.1)
4 (2.1)
2 (1.1)
0
1 (0.5)
0
2 (1.1)
2 (1.1)
0
Fatal AEs, n (%)
10 (5.2)
11 (5.9)
*AE reporting period: up to 90 days after end of bendamustine and rituximab treatment (maximum six months); up to 28 days after end of venetoclax and rituximab treatment (maximum two years).
About VENCLEXTA/VENCLYXTO
VENCLEXTA/VENCLYXTO is an oral B-cell lymphoma-2 (BCL-2) inhibitor that targets a specific protein in the body called BCL-2.2,5 When you have CLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally.2,5 VENCLEXTA/VENCLYXTO targets BCL-2 in order to help restore the process of apoptosis.2,5 Through apoptosis, your body allows cancer cells and normal cells to self-destruct.2,5

VENCLEXTA/VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in clinical trials in several hematologic cancers.

VENCLEXTA/VENCLYXTO is currently approved in 49 nations, including the U.S., and in the EU. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to eligible patients in need.

About VENCLYXTO (venetoclax) Tablets (EU)
VENCLYXTO (venetoclax) is indicated in the European Union (EU) for the treatment of chronic lymphocytic leukemia (CLL) in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.5 It is also being evaluated for the treatment of patients with various blood cancer types. 1,6,7,8,9 The BCL-2 protein prevents apoptosis (programmed cell death) of some cells, including lymphocytes, and can be overexpressed in CLL cells.1 VENCLYXTO, which is given once-daily, is designed to selectively inhibit the function of the BCL-2 protein.1

Important VENCLYXTO (venetoclax) EU Safety Information
Contraindications
Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase. Concomitant use of preparations containing St. John’s wort.

Special Warnings & Precautions for Use
Tumor lysis syndrome (TLS), including fatal events, has occurred in patients with previously treated CLL with high tumor burden when treated with VENCLYXTO. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS. Blood chemistries should be monitored and abnormalities managed promptly. More intensive measures (including IV hydration, frequent monitoring and hospitalization) should be employed as overall risk increases.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions
CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: If moderate or strong CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations.

Avoid co-administration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions
The most commonly occurring adverse reactions (>=20%) of any grade were neutropenia/neutrophil count decreased, diarrhea, nausea, anemia, upper respiratory tract infection, fatigue, hyperphosphatemia, vomiting and constipation.

The most frequently occurring adverse reactions (>=2%) were pneumonia, febrile neutropenia and TLS.

Discontinuations due to adverse reactions occurred in 9.1% of patients and dosage adjustments due to adverse reactions occurred in 11.8% of patients.

Specific Populations
VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise females of reproductive potential to avoid pregnancy during treatment. Advise nursing women to discontinue breastfeeding during treatment.

Safety in patients with severe renal impairment or on dialysis has not been established, and a recommended dose has not been determined. VENCLYXTO should be administered to patients with severe renal impairment only if the benefit outweighs the risk. Monitor closely for signs of toxicity due to increased risk of TLS.

This is not a complete summary of all safety information. See VENCLYXTO full summary of product characteristics (SmPC) at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

About VENCLEXTA (venetoclax) tablets (US)
In April 2016, the U.S. Food and Drug Administration (FDA) granted accelerated approval of VENCLEXTA (venetoclax) tablets for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.2 The FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.

VENCLEXTA has been granted four Breakthrough Therapy Designations from the FDA including for the combination treatment of patients with untreated AML not eligible for standard induction chemotherapy. This designation is intended to expedite the development and review of therapies for serious or life-threatening conditions.10 In January 2016, AbbVie announced that the FDA granted priority review for the single agent NDA application for VENCLEXTA.

In November 2017, AbbVie and Genentech received the Prix Galien award for "Best Pharmaceutical Product" for VENCLEXTA.11

What is VENCLEXTA (venetoclax)?
VENCLEXTA (venetoclax) is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) with 17p deletion who have received at least one prior treatment.

VENCLEXTA was approved based on response rate. There is an ongoing study to find out how VENCLEXTA works over a longer period of time.

It is not known if VENCLEXTA is safe and effective in children.

Important VENCLEXTA (venetoclax) US Safety Information

What is the most important information I should know about VENCLEXTA?
VENCLEXTA can cause serious side effects, including:
Tumor lysis syndrome (TLS). TLS is caused by the fast breakdown of cancer cells. TLS can cause kidney failure, the need for dialysis treatment, and may lead to death. Your doctor will do tests for TLS. It is important to keep your appointments for blood tests. You will receive other medicines before starting and during treatment with VENCLEXTA to help reduce your risk of TLS. You may also need to receive intravenous (IV) fluids into your vein. Tell your doctor right away if you have any symptoms of TLS during treatment with VENCLEXTA, including fever, chills, nausea, vomiting, confusion, shortness of breath, seizures, irregular heartbeat, dark or cloudy urine, unusual tiredness, or muscle or joint pain.

Drink plenty of water when taking VENCLEXTA to help reduce your risk of getting TLS. Drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before your first dose, on the day of your first dose of VENCLEXTA, and each time your dose is increased.

Who should not take VENCLEXTA?
Certain medicines must not be taken when you first start taking VENCLEXTA and while your dose is being slowly increased.

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. VENCLEXTA and other medicines may affect each other, causing serious side effects.
Do not start new medicines during treatment with VENCLEXTA without first talking with your doctor.
What should I tell my doctor before taking VENCLEXTA?
Before taking VENCLEXTA, tell your doctor about all of your medical conditions, including if you:

Have kidney or liver problems.
Have problems with your body salts or electrolytes, such as potassium, phosphorus, or calcium
Have a history of high uric acid levels in your blood or gout
Are scheduled to receive a vaccine. You should not receive a "live vaccine" before, during or after treatment with VENCLEXTA until your doctor tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your doctor. These vaccines may not be safe or may not work as well during treatment with VENCLEXTA.
Are pregnant or plan to become pregnant. VENCLEXTA may harm your unborn baby. If you are able to become pregnant, your doctor should do a pregnancy test before you start treatment with VENCLEXTA, and you should use effective birth control during treatment and for 30 days after the last dose of VENCLEXTA.
Are breastfeeding or plan to breastfeed. It is not known if VENCLEXTA passes into your breast milk. Do not breastfeed during treatment with VENCLEXTA.
What should I avoid while taking VENCLEXTA?
You should not drink grapefruit juice or eat grapefruit, Seville oranges (often used in marmalades), or starfruit while you are taking VENCLEXTA. These products may increase the amount of VENCLEXTA in your blood.

What are the possible side effects of VENCLEXTA?
VENCLEXTA can cause serious side effects, including:

Low white blood cell count (neutropenia). Low white blood cell counts are common with VENCLEXTA, but can also be severe. Your doctor will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your doctor right away if you have a fever or any signs of an infection.
The most common side effects of VENCLEXTA include low white blood cell count, diarrhea, nausea, low red blood cell count, upper respiratory tract infection, low platelet count, and feeling tired.

VENCLEXTA may cause fertility problems in males. This may affect your ability to father a child. Talk to your doctor if you have concerns about fertility.

These are not all the possible side effects of VENCLEXTA. Tell your doctor if you have any side effect that bothers you or that does not go away.

The full U.S. prescribing information for VENCLEXTA can be found here. Globally, prescribing information varies; refer to the individual country product label for complete information.

Patient Assistance
For those who qualify, patient assistance options are available for people taking VENCLEXTA in the U.S.

About AbbVie in Oncology
At AbbVie, we strive to discover and develop medicines that deliver transformational improvements in cancer treatment by uniquely combining our deep knowledge in core areas of biology with cutting-edge technologies, and by working together with our partners – scientists, clinical experts, industry peers, advocates, and patients. We remain focused on delivering these transformative advances in treatment across some of the most debilitating and widespread cancers. We are also committed to exploring solutions to help patients obtain access to our cancer medicines. With the acquisitions of Pharmacyclics in 2015 and Stemcentrx in 2016, our research and development efforts, and through collaborations, AbbVie’s oncology portfolio now consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in more than 200 clinical trials and more than 20 different tumor types. For more information, please visit View Source

On December 12, 2017 Servier, Pfizer Inc. (NYSE: PFE) and Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext Growth: ALCLS – Nasdaq: CLLS) presented at the the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta reported preliminary results from two phase 1 studies of UCART19, an investigational allogeneic anti-CD19 CAR T-cell product, in adult and pediatric patients with relapsed or refractory (R/R) CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) (Press release, Cellectis, DEC 12, 2017, View Source [SID1234522628]). These first-in-human data demonstrated the safety and tolerability of UCART19, resulting in an 83% complete remission rate across the adult and pediatric patient population.

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Results from the CALM (UCART19 in Advanced Lymphoid Malignancies) Trial

The CALM study (UCART19 in Advanced Lymphoid Malignancies) is an open label, dose-escalation study designed to evaluate the safety, tolerability and anti-leukemic activity of UCART19 in adult patients with R/R B-ALL. Five out seven patients treated achieved molecular remission at Day 28 post UCAR19. Molecular remission is defined by negative minimal residual disease (MRD). MRD is a measurement of the number of residual leukemic cells that remain after treatment.

"These early results for UCART19 are very encouraging both in terms of manageable safety and the impressive complete molecular remission rate in these hard-to-treat adult patients with R/R B-ALL," said Reuben Benjamin, Principal Investigator of the CALM Study and Consultant Hematologist at King’s College Hospital, United Kingdom. "This first cohort explored a lower dose of UCART19 that is approximately one tenth of that used in most autologous CAR-T trials. These results support additional evaluation of UCART19 at varying doses."

Only one Grade 1 cutaneous acute graft versus host disease (GvHD) occurred. No severe neurotoxicity was observed. Cytokine release syndromes (CRS) were mild and manageable except in one patient treated with UCART19 at the first dose level, who developed CRS Grade 4 and neutropenic sepsis leading to death at Day 15.

Results from the PALL (Pediatric Acute Lymphoblastic Leukemia) Trial

The PALL (Pediatric Acute Lymphoblastic Leukemia) study is a phase 1, open label study designed to evaluate the safety and ability of UCART19 to induce molecular remission defined by MRD negativity at Day 28 to enable allogeneic stem cell transplantation in pediatric patients with high-risk R/R B-ALL. Results showed all five children achieved MRD negativity, enabling them to proceed to allogeneic stem cell transplant. Only one Grade 1 cutaneous acute GvHD occurred. No severe neurotoxicity was observed. Cytokine release syndromes were mild in the majority of cases and were all manageable.

Servier is the sponsor of both studies that are active in Europe and the United States.

"We are proud to present the first clinical trial data with UCART19 in patients with heavily pretreated R/R ALL," said Patrick Therasse, MD, PhD, Head of Research and Development-Oncology for Servier. "We believe this innovative, allogeneic CAR T-cell approach could be disruptive to the patient community."

About UCART19

UCART19 is an allogeneic CAR T-cell product candidate being developed for treatment of CD19-expressing hematological malignancies, gene edited with TALEN. UCART19 is initially being developed in adult and pediatric ALL and is currently in Phase I. UCART19 has the potential to overcome the limitation of the current autologous approach by providing an allogeneic, frozen, "off-the-shelf" T cell based medicinal product.

In November 2015, Servier acquired the exclusive rights to UCART19 from Cellectis. Following further agreements, Servier and Pfizer began collaborating on a joint clinical development program for this cancer immunotherapy. Pfizer has been granted exclusive rights by Servier to develop and commercialize UCART19 in the United States, while Servier retains exclusive rights for all other countries.

About Servier

Servier is an international pharmaceutical company governed by a non-profit foundation, with its headquarters in France (Suresnes). With a strong international presence in 148 countries and a turnover of 4 billion euros in 2016, Servier employs 21 000 people worldwide. Entirely independent, the Group reinvests 25% of its turnover (excluding generic drugs) in research and development and uses all its profits for development. Corporate growth is driven by Servier’s constant search for innovation in five areas of excellence: cardiovascular, immune-inflammatory and neuropsychiatric diseases, cancers and diabetes, as well as by its activities in high-quality generic drugs.

Becoming a key player in oncology is part of Servier’s long-term strategy. Currently, there are nine molecular entities in clinical development in this area, targeting gastric and lung cancers and other solid tumors, as well as various leukemias and lymphomas. This portfolio of innovative cancer treatments is being developed with partners worldwide, and covers different cancer hallmarks and modalities, including cytotoxics, proapoptotics, targeted, immune and cellular therapies, to deliver life-changing medicines to patients. More information: View Source

Pfizer Inc.: Working together for a healthier world

At Pfizer, we apply science and our global resources to bring therapies to people that extend and significantly improve their lives. We strive to set the standard for quality, safety and value in the discovery, development and manufacture of health care products. Our global portfolio includes medicines and vaccines as well as many of the world’s best-known consumer health care products. Every day, Pfizer colleagues work across developed and emerging markets to advance wellness, prevention, treatments and cures that challenge the most feared diseases of our time. Consistent with our responsibility as one of the world’s premier innovative biopharmaceutical companies, we collaborate with health care providers, governments and local communities to support and expand access to reliable, affordable health care around the world. For more than 150 years, we have worked to make a difference for all who rely on us. We routinely post information that may be important to investors on our website at www.pfizer.com. In addition, to learn more, please visit us on www.pfizer.com and follow us on Twitter at @Pfizer and @Pfizer_News, LinkedIn, YouTube, and like us on Facebook at Facebook.com/Pfizer.

PFIZER DISCLOSURE NOTICE

The information contained in this release is as of December 12, 2017. Pfizer assumes no obligation to update forward-looking statements contained in this release as the result of new information or future events or developments.

This release contains forward-looking information about a product candidate, UCART19, including its potential benefits, that involves substantial risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statements. Risks and uncertainties include, among other things, the uncertainties inherent in research and development, including the ability to meet anticipated clinical study commencement and completion dates as well as the possibility of unfavorable study results, including unfavorable new clinical data and additional analyses of existing clinical data; risks associated with preliminary data; the risk that clinical trial data are subject to differing interpretations, and, even when we view data as sufficient to support the safety and/or effectiveness of a product candidate, regulatory authorities may not share our views and may require additional data or may deny approval altogether; whether regulatory authorities will be satisfied with the design of and results from our clinical studies; whether and when drug applications may be filed for UCART19 in any jurisdiction; whether and when any such applications may be approved by regulatory authorities, which will depend on the assessment by such regulatory authorities of the benefit-risk profile suggested by the totality of the efficacy and safety information submitted, and, if approved, whether UCART19 will be commercially successful; decisions by regulatory authorities regarding labeling and other matters that could affect the availability or commercial potential of UCART19; and competitive developments.

A further description of risks and uncertainties can be found in Pfizer’s Annual Report on Form 10-K for the fiscal year ended December 31, 2016 and in its subsequent reports on Form 10-Q, including in the sections thereof captioned "Risk Factors" and "Forward-Looking Information and Factors That May Affect Future Results", as well as in its subsequent reports on Form 8-K, all of which are filed with the U.S. Securities and Exchange Commission and available at www.sec.gov and www.pfizer.com.