On July 12, 2018 AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, reported it submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) for venetoclax in combination with a hypomethylating agent (HMA) or in combination with low-dose cytarabine (LDAC) for the treatment of newly diagnosed patients with acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (Press release, AbbVie, JUL 12, 2018, View Source [SID1234527661]).

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The sNDA submission is based on investigational data from two studies: M14-358, a Phase 1b trial evaluating venetoclax in combination with an HMA (azacitidine or decitabine), and M14-387, a Phase 1/2 trial of venetoclax in combination with LDAC.

"AML is an especially lethal and aggressive form of blood cancer with limited advances in care in three decades and few treatment options for patients ineligible for intensive chemotherapy," said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "The data submitted to the FDA may potentially reshape how AML is treated. We look forward to working with the FDA and other health authorities during the review of these data."

AML, primarily a disease of older patients, is the most common form of acute leukemia in adults, in which the bone marrow makes abnormal, immature types of white blood cells, red blood cells or platelets.2,3 AML is an aggressive blood cancer that, if left untreated, can progress quickly.2 In the U.S., it is estimated there will be 19,520 new cases and 10,670 deaths due to AML in 2018.3

Approximately 27 percent of patients diagnosed with AML will survive five years or more.3 Disease recurrence occurs in most patients with AML within three years of diagnosis.1,4,5 Although few treatments are available, AML patients who are ineligible for intensive remission induction therapy may be treated with LDAC or HMAs.1,6 Only about one-third of AML patients older than age 60 are able to tolerate the intensive chemotherapy required to achieve optimal results.7 Median survival is five to 10 months in older AML patients who are ineligible for intensive chemotherapy.1

The challenges of treating AML, including in older adults, is an ongoing topic of discussion among the medical community. Daniel Pollyea, M.D., director of Leukemia Services at University of Colorado Hospital, recently reflected on his experience treating patients with AML. "We have an incredible opportunity to develop better treatment options for people with AML. Still, right now every aspect of this disease represents an unmet need," he said. For more on Dr. Pollyea’s perspective, please read "A Physicians View: Facing the Challenges of Treating AML in Older Adults."

Venetoclax, an oral B-cell lymphoma-2 (BCL-2) inhibitor, has been granted four Breakthrough Therapy Designations (BTDs) from the FDA including for the combination of venetoclax with an HMA (azacitidine or decitabine) for treatment-naïve patients with AML who are ineligible to receive standard induction therapy (high-dose chemotherapy) and for the combination of venetoclax with LDAC for treatment-naïve patients with AML who are ineligible for intensive chemotherapy. According to the FDA, BTD is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).8

If approved in AML, venetoclax would be available for use in two blood cancers, chronic lymphocytic leukemia (CLL) and AML. Venetoclax recently received expanded approval in the U.S. for use alone or in combination with rituximab for the treatment of relapsed/refractory (R/R) CLL or small lymphocytic lymphoma (SLL) patients, with or without 17p deletion, who have received at least one prior therapy.9

In addition to CLL and AML, venetoclax is being studied in a range of hematologic malignancies including multiple myeloma (MM), non-Hodgkin lymphoma (NHL) and myelodysplastic syndrome (MDS).10,11,12 Venetoclax is being developed by AbbVie and Roche and 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.10,11,12,13,14

Additional information regarding venetoclax clinical trials is available on www.clinicaltrials.gov.

About VENCLEXTA (venetoclax tablets) (US)

VENCLEXTA is an oral BCL-2 inhibitor that targets a specific protein in the body called BCL-2.9 When you have CLL or SLL, BCL-2 may build up and prevent cancer cells from self-destructing naturally. VENCLEXTA targets BCL-2 in order to help restore the process of apoptosis.9

VENCLEXTA 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.

VENCLEXTA (VENCLYXTO in the EU) is currently approved as a monotherapy in 53 nations, including the U.S. AbbVie, in collaboration with Roche and Genentech, is currently working with regulatory agencies around the world to bring this medicine to additional eligible patients in need.

VENCLEXTA was first approved in April 2016 when the U.S. FDA granted accelerated approval of VENCLEXTA 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.15 The FDA approved this indication under accelerated approval based on overall response rate.15 Based on the results of the MURANO study, VENCLEXTA was approved in June 2018 for the treatment of patients with CLL or SLL, with or without 17p deletion, who have received at least one prior therapy in combination with rituximab or as monotherapy.9

Use and Important Safety Information (US)

Use
What is VENCLEXTA (venetoclax tablets)?
VENCLEXTA is a prescription medicine used to treat people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with or without 17p deletion, who have received at least one prior treatment.

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

Important VENCLEXTA (venetoclax tablets) 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 health care provider 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 health care provider 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 because of the risk of increased tumor lysis syndrome.

Tell your health care provider 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 health care provider.
Before taking VENCLEXTA, tell your health care provider 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 health care provider tells you it is okay. If you are not sure about the type of immunization or vaccine, ask your health care provider. 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 health care provider 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, 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 health care provider will do blood tests to check your blood counts during treatment with VENCLEXTA. Tell your health care provider right away if you have a fever or any signs of an infection.
The most common side effects of VENCLEXTA when used in combination with rituximab include low white blood cell count, diarrhea, upper respiratory tract infection, cough, tiredness, and nausea.

The most common side effects of VENCLEXTA when used alone include low white blood cell count, diarrhea, nausea, upper respiratory tract infection, low red blood cell count, tiredness, low platelet count, muscle pain and joint pain, swelling or your arms, legs, hands, and feet, and cough.

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

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

People are encouraged to report negative side effects of prescription drug to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

The full U.S. prescribing information, including Medication Guide, 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. If people cannot afford their medication, they should contact www.pparx.org for assistance.

On July 12, 2018 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported that it will report its second quarter 2018 financial results on Wednesday, July 25, 2018 after the financial markets close (Press release, Vertex Pharmaceuticals, JUL 12, 2018, View Source [SID1234527679]). The company will host a conference call and webcast at 4:30 p.m. ET. To access the call, please dial (866) 501-1537 (U.S.) or +1 (720) 545-0001 (International).

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The conference call will be webcast live and a link to the webcast can be accessed through Vertex’s website at www.vrtx.com in the "Investors" section. To ensure a timely connection, it is recommended that participants register at least 15 minutes prior to the scheduled webcast. An archived webcast will be available on the company’s website.

On July 12, 2018 EUSA Pharma reported that a decision by the National Institute for Health and Care Excellence (NICE) to recommend the use of the targeted cancer immunotherapy, QARZIBA (dinutuximab beta) to treat children with high-risk neuroblastoma within the NHS in England and Wales (Press release, EUSA Pharma, JUL 12, 2018, View Source [SID1234527662]).[i] High-risk neuroblastoma is an aggressive form of neuroblastoma – the most common solid tumour of childhood that originates outside of the brain.[ii] Dinutuximab beta is the first targeted cancer immunotherapy approved for use on the NHS to treat this disease. It has been shown in a post-hoc analysis to improve overall survival (OS) outcomes compared to historically treated patients who did not receive immunotherapy as part of their care. Dinutuximab beta, when used in the maintenance phase of treatment for patients who did not receive prior immunotherapy, is also used to keep this cancer from returning or progressing in some children with high-risk neuroblastoma.ii

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"Today’s decision by NICE is a vital step forward in the treatment of young children with this aggressive type of cancer," said Dr Juliet Gray, Associate Professor in Paediatric Oncology at the Cancer Immunology Centre, University of Southampton. "By harnessing the body’s own immune system, dinutuximab beta has shown it can target and attack this cancer very effectively in some patients. For some children this could mean extra weeks or months with their families, for others it may even lead to them becoming cancer-free for a long period of time."

Dinutuximab beta is a monoclonal antibody (a type of protein) that binds to a specific target which is overexpressed on neuroblastoma cells, called GD2.[iii] This induces dual immune mechanisms that then enable the immune system to lead the destruction of neuroblastoma cancer cells.ii In the key phase III clinical study (APN311-302), a post hoc comparison of dinutuximab beta, used in the maintenance phase of the first-line treatment of high-risk neuroblastoma (n=367) , showed improved survival outcomes, with a 12% improvement in OS rate at three years versus using no immunotherapy in a historical control group of similar patients (n=450).ii The dinutuximab beta treated patients had an OS rate of around 65% at 5 years versus 50% compared to the historical control group (p=<0.0001).ii

Tony Heddon, Chair of Neuroblastoma UK commented: "Ensuring that children and families facing high-risk neuroblastoma have access to the medicines and care they need is absolutely critical. Today’s recommendation is a bold and forward-thinking decision from NICE and we applaud them, EUSA Pharma and all those across the community who have worked together to make this medicine available. This decision offers the hope that these children with high-risk neuroblastoma, may now have a better future in front of them."

On average, every week, two families in the UK will learn that their child has neuroblastoma, with approximately 100 children diagnosed each year.[iv] It is the most frequently-occurring solid tumour in infants under the age of one, accounting for around a fifth (22%) of all cancers diagnosed at this age.[v] Children with high-risk disease to whom this approval applies, account for approximately 40% of all neuroblastoma cases.[vi] Children with high-risk neuroblastoma typically undergo many rounds of complex and intensive treatment, usually comprising several cycles of chemotherapy, surgery, stem cell transplant and radiotherapy.[vii]

The recommendation from NICE within its Final Appraisal Determination (FAD) is that dinutuximab beta be used as an option for treating high-risk neuroblastoma after at least a partial response from induction chemotherapy, followed by myeloablative therapy and stem cell transplant in people aged 12 months and over, if the person has not had previous anti-GD2 immunotherapy.i

Lee Morley, CEO of EUSA Pharma added: "Today’s decision is the result of strong collaboration between NICE, EUSA Pharma and the neuroblastoma community, who have each worked tirelessly to ensure that every eligible child has the option to benefit from this potentially life-changing treatment. Our long-standing commitment has always been to secure access to dinutuximab beta for all eligible children with high-risk neuroblastoma, across the UK and today’s decision is a key part of that journey. Beyond England and Wales, we are continuing to work closely with the Scottish and Northern Irish health authorities with the aim of making this medicine available in those countries as quickly as possible."

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcardreporting. Adverse events should also be reported to EUSA Pharma. Email: [email protected] Fax: +44(0)3305 001167

About dinutuximab beta

How it works

Dinutuximab beta is a monoclonal antibody (a type of protein) that has been designed to recognise and attach to a tumour-associated carbohydrate structure, called GD2, which is present in high amounts on the surface of neuroblastoma cells.ii When dinutuximab beta attaches to the neuroblastoma cells, it induces dual immune system mechanisms (the complement-dependant and antibody-dependant cell-mediated immune pathways) and makes them a target for the body’s immune system. This then mounts an attack to kill the cancer cells, using the body’s natural killer immune cells, and the complement protein system.ii

It’s development and approval

Dinutuximab beta is the result of a considered science–pharma collaboration. Dinutuximab beta was developed by Apeiron Biologics with a number of partners (in particular the SIOPEN academic neuroblastoma group) and acquired by EUSA Pharma in 2016, to bring the treatment to market. Dinutuximab beta received European approval in May 2017, first under the brand names dinutuximab beta Apeiron and Dinutuximab beta EUSA and subsequently under its new name, QARZIBA, approved by the European Medicines Agency in November 2017.iii

How it is taken

Dinutuximab beta is given as an infusion (drip) into a vein. Each course of treatment with the medicine is given for 5 or 10 days every 35 days. It is given for a total of 5 courses. The recommended dose depends on the patient’s weight and height.iii

Data supporting its use

Dinutuximab beta has been investigated in a number of clinical trials for high-risk neuroblastoma.ii During the NICE appraisal, the primary clinical evidence came from APN311-302, a multinational, open-label, randomised, controlled Phase III trial comparing dinutuximab beta plus isotretinoin (n=189) with dinutuximab beta plus isotretinoin plus interleukin-2 (n=190).i,ii The primary outcome in the trial was event-free survival at three years (disease progression or relapse, death and secondary tumour defined as events) with OS, overall response, and incidence of relapsed or refractory disease included as secondary outcomes.ii This study consisted of up to five different comparison phases, one of which was treatment with dinutuximab beta with or without interleukin-2 (IL-2) during the maintenance phase , in the first line setting.ii

In APN311-302, the 3-year event free survival (primary endpoint) showed rates of 55% without IL-2 and 61% with IL-2 (p=0.3202) while the 3-year OS rates were 64% and 69%, respectively (p=0.6114).i A comparison to an historical control group obtained from an earlier patient enrolment within the APN311-302 study (between 2002 and 2010) was performed using 450 high-risk neuroblastoma patients, who did not receive immunotherapy. Given the relatively high number of patients it is expected that these patients are representative of patients with high-risk neuroblastoma seen in clinical practice during this period. This comparison showed that the percentage of patients that were still alive after three years of follow-up was 12% higher after dinutuximab beta treatment (with or without IL-2) than for patients who did not receive immunotherapy, a difference considered clinically relevant.ii It also showed an OS rate of around 65% at 5 years with dinutuximab beta versus 50% in the historical control group (p=<0.0001).ii

At marketing authorisation, the European Medicines Agency considered that the available data set was not comprehensive and that measures were necessary to generate additional efficacy and safety data. EUSA Pharma is committed to this and is continuing to collect further data to widen the body of efficacy and safety information available on this medicine.ii

Side effects

Side effects with dinutuximab beta are common. In general, the most common side effects with dinutuximab beta (which may affect more than 7 in 10 people) are pyrexia (fever) and pain. Other side effects (which may affect more than 3 in 10 people) are hypersensitivity (allergy), vomiting, diarrhoea, capillary leak syndrome (leakage of fluid from blood vessels that can cause swelling and a drop in blood pressure) and hypotension (low blood pressure).iii

In the APN311-302 study, 98.9% of patients (362 of 366) in both treatment group experienced toxicities. Serious adverse events were reported more frequently in patients receiving IL-2 (46% of 183 patients) compared to patients not receiving IL-2 (27% of 183 patients). Serious adverse events leading to discontinuation of treatment were more frequent in the IL2 arm than the group without IL2,17% vs 6% of patients, respectively.ii

On July 12, 2018 Incyte Corporation (Nasdaq:INCY) reported that it has scheduled its second quarter 2018 financial results conference call and webcast for 8:00 a.m. ET on Tuesday, July 31, 2018 (Press release, Incyte, JUL 12, 2018, View Source [SID1234527680]).

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The schedule for the press release and conference call/webcast is as follows:

Q2 2018 Press Release: July 31, 2018 at 7:00 a.m. ET

Q2 2018 Conference Call: July 31, 2018 at 8:00 a.m. ET

Domestic Dial-In Number: 877-407-3042

International Dial-In Number:

201-389-0864

Conference ID Number: 13681303

If you are unable to participate, a replay of the conference call will be available for thirty days. The replay dial-in number for the U.S. is 877-660-6853 and the dial-in number for international callers is 201-612-7415. To access the replay you will need the conference ID number 13681303.

The live webcast with slides can be accessed at www.incyte.com under For Investors, Events and Presentations and will be available for replay for 30 days.

On July 12, 2018 Compass Therapeutics, a biotechnology company committed to the ambitious goal of comprehensively drugging the human immune system, reported the closing of the final $49 million of its $132 million Series A financing. This financing will enable the company to advance its next-generation antibody-based therapeutics into the clinic (Press release, Compass Therapeutics, JUL 12, 2018, View Source [SID1234529743]). The financing was led by OrbiMed Advisors and included F-Prime Capital, Cowen Healthcare Investments, Thiel Capital, Biomatics Capital, Ulysses Holdings, Borealis Ventures, Alexandria Venture Investments and Biomed Realty Ventures.

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Compass is pioneering a new approach to identifying antibody drug candidates that engage all targets in the biologically complex human immune synapse, with an initial focus on T cells, NK cells and macrophages. The company’s antibody discovery and bispecific engineering platforms enable the rapid identification of therapeutic candidates that engage with a broad range of epitopes on every target. Specifically, StitchMabs, a novel and proprietary high-throughput bispecific screening platform, enables the rapid identification of synergistic bispecific activity.

The antibody discovery platform is both robust and efficient. Compass is capable of drugging two new targets per month, and therapeutic candidates are generated in less than two months from antigen to candidate set. To date, the integrated R&D approach has generated therapeutic candidates for more than 30 targets in cancer, inflammation and autoimmune disease. Compass has more than 15 therapeutic candidates advancing through preclinical development and has filed more than 50 patent applications.

CTX-471, the company’s leading immuno-oncology candidate, is in late IND-enabling studies and is expected to enter the clinic in the first half of 2019. It has been tested across multiple in vitro and in vivo models and has consistently shown potent and durable curative activity as a single agent, in combination with other immune-modulatory agents and with tumor-targeting therapies. In addition, in stringent high tumor burden therapeutic models, CTX-471 has led to complete tumor rejections and the generation of long-term, protective immunological memory.

Upon final closing of the financing round, Thomas Schuetz, M.D., Ph.D., the company’s co-founder and chief executive officer, commented: "The proceeds from this round will be used to rapidly advance our first therapeutic candidate, CTX-471, into the clinic, and to nominate two additional clinical candidates by the end of this year. I am grateful for our strong investor syndicate that has continued to support the company since its inception."

Carl Gordon, Ph.D., a board member and managing partner at OrbiMed Advisors, commented: "In the three years since the initial Series A closing, Compass has built a portfolio of antibody discovery, bispecific engineering and functional characterization platforms which has consistently delivered novel and differentiated antibody drug candidates. Compass is positioned to become a leader in the fields of immuno-oncology, inflammation and autoimmune disease."

Compass is also focused on drugging targets at the intersection of the innate and the adaptive immune response. By screening all discovery sets for both activating and inhibiting signaling, Compass is developing a set of novel therapeutics to induce tolerance in patients with autoimmune diseases.

"With every target we pursue, we are pushing the boundaries of its epitopic diversity. We then create multiple formats of antibody-based multispecific drugs to empirically test various therapeutic hypotheses. Our unique StitchMabs technology allows us to screen for bispecific synergies in a high-throughput manner, and the output from our discovery platforms is compatible with highly modular bispecific engineering strategies," said Piotr Bobrowicz, Ph.D., the company’s chief scientific officer.