On December 3, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), reported new data from the Venclexta (venetoclax) clinical development program, including longer-term results from the Phase III MURANO study in people with previously treated chronic lymphocytic leukemia (CLL) and updated data from two Phase Ib/II studies in people with previously untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy due to coexisting medical conditions (Press release, Genentech, DEC 3, 2018, View Source [SID1234531846]). Data from the Venclexta clinical development program that ranges across multiple blood cancers, including CLL, AML, non-Hodgkin’s lymphoma and multiple myeloma, will be featured in more than 30 abstracts, including 12 oral presentations, at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) 2018 Annual Meeting.

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"We’re excited by the versatility of Venclexta in treating a range of distinct types of blood cancer, including difficult-to-treat forms with limited options," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "These data support our broad clinical development program through which we hope to discover more ways Venclexta can be used alone or in combination with other medicines to treat additional types of cancer."

Updated Data in CLL

Two new analyses of the Phase III MURANO study in relapsed or refractory (R/R) CLL demonstrated the continued clinical benefit of Venclexta plus Rituxan (rituximab) was sustained after patients completed the chemotherapy-free, two-year fixed-duration course of therapy.

An analysis showed the combination reduced the risk of disease progression or death (progression-free survival; PFS, as assessed by investigator) by 84 percent (HR=0.16; 95 percent CI: 0.12-0.23; p<0.0001) compared to standard of care bendamustine plus Rituxan (BR) after a median three-year follow-up. At three years, 71 percent of patients in the Venclexta plus Rituxan arm had not experienced disease progression, compared to 15 percent of patients in the BR arm (median PFS: not reached vs. 17.0 months, respectively). A clinically meaningful benefit in overall survival was also observed in the Venclexta arm compared to the BR arm (88 percent vs. 80 percent, HR=0.50; 95 percent CI: 0.30-0.85). Consistent benefit was observed in all patient subgroups for Venclexta plus Rituxan compared to BR, including high-risk and low-risk groups. Data were presented in an oral session on Saturday, December 1, at 2:45 P.M. PST (Abstract #184).
A separate analysis showed higher rates of minimal residual disease (MRD)-negativity observed with Venclexta plus Rituxan compared to BR were sustained after patients completed treatment (62 percent vs. 13 percent). MRD-negativity means no cancer can be detected using a specific, highly sensitive test, and was defined as less than 1 CLL cell in 10,000 leukocytes. Importantly, these results were observed in the majority of patients in the Venclexta arm, including patients in high-risk subgroups and were consistent with the maintained PFS benefit seen with longer follow-up. These data support the utility of MRD in peripheral blood as a predictive marker of clinical outcome. No new safety signals were observed with the treatment combination of Venclexta plus Rituxan. These data will be presented in an oral session on Monday, December 3, at 11:30 A.M. PST (Abstract #695).
Updated Data in AML

Updated data from the Phase Ib M14-358 and Phase I/II M14-387 studies evaluating Venclexta in combination with a hypomethylating agent or low-dose cytarabine (LDAC) in people with previously untreated AML who are ineligible for intensive chemotherapy will also be presented. These results showed that among patients who were dependent upon blood transfusions at baseline, about half were able to achieve transfusion independence (the absence of transfusions during any consecutive 56 days during the study treatment period). No unexpected safety signals were observed with Venclexta in combination with hypomethylating agents or LDAC.

The M14-358 study showed high rates of complete remission (with at least partial blood count recovery, CR+CRh) of 67 percent for those who received Venclexta plus azacitidine and 71 percent for those who received Venclexta plus decitabine. For people taking Venclexta and azacitadine or decitabine who were dependent on blood transfusions at baseline, 50 percent and 52 percent achieved red blood cell transfusion independence, respectively; and 58 percent or 60 percent achieved platelet transfusion independence, respectively.
The M14-387 study showed rates of complete remission (with or without full recovery of normal blood cell count, CR+CRi) of 54 percent in people who received Venclexta in combination with LDAC and a median duration of remission of 8.1 months. For people taking Venclexta with LDAC, 48 percent achieved red blood cell transfusion independence and 60 percent achieved platelet transfusion independence.
Results from the two studies were presented in an oral session on Sunday, December 2 at 7:45 A.M. PST and 8:00 A.M. PST, respectively (Abstract #284 and #285).

Based on earlier results from the M14-358 and M14-387 studies, Venclexta was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for the treatment of people with newly-diagnosed AML who are age 75 years or older, or for those ineligible for intensive induction chemotherapy due to coexisting medical conditions. A robust clinical development program for Venclexta in AML is ongoing, including two ongoing Phase III studies evaluating Venclexta in combination with azacitidine or with LDAC for people with previously untreated AML who are ineligible for intensive chemotherapy based on results from the M14-358 and M14-387 studies.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and commercialized by AbbVie outside of the U.S.

About the MURANO study

MURANO (NCT02005471) is a Phase III open-label, international, multicenter, randomized study evaluating the efficacy and safety of Venclexta in combination with Rituxan compared to bendamustine in combination with Rituxan (BR). All treatments were of fixed duration. Following a five-week dose ramp-up schedule for Venclexta, patients on the Venclexta plus Rituxan arm received six cycles of Venclexta plus Rituxan followed by Venclexta monotherapy for up to two years total. Patients on the BR arm received six cycles of BR. The study included 389 patients with chronic lymphocytic leukemia (CLL) who had been previously treated with at least one line of therapy. Patients were randomly assigned in a 1:1 ratio to receive either Venclexta plus Rituxan or BR. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS), overall response rate (ORR) and complete response rate (with or without complete blood count recovery, CR/CRi).

About the M14-358 study

The M14-358 study (NCT02203773) is an open-label, non-randomized, Phase Ib dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with hypomethylating agents, azacitidine or decitabine, in 115 newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, transfusion independence, overall survival and safety.

About the M14-387 study

The M14-387 study (NCT02287233) is an open-label, single-arm, Phase I/II dose escalation and expansion study evaluating the safety and efficacy of Venclexta in combination with LDAC in 82 newly-diagnosed people with AML who were 60 years or older, or ineligible to receive intensive induction chemotherapy due to coexisting medical conditions. Study endpoints included complete remission rates, transfusion independence, overall survival and safety.

About CLL

Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, and in 2018, it is estimated there will be more than 20,000 new cases of CLL diagnosed in the United States. Although signs of CLL may disappear for a period of time after initial treatment, the disease is considered incurable and many people will require additional treatment due to the return of cancerous cells.

About AML

Acute myeloid leukemia (AML) is the most common type of aggressive leukemia in adults, which has the lowest survival rate for all types of leukemia. In 2018, it is estimated there will be nearly 20,000 new cases of AML diagnosed in the United States. Many AML patients older than age 60 are unable to tolerate standard intensive chemotherapy treatment.

About Venclexta

Venclexta is a first-in-class targeted medicine designed to selectively bind and inhibit the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers and other tumors, BCL-2 builds up and prevents cancer cells from dying or self-destructing, a process called apoptosis. Venclexta blocks the BCL-2 protein and works to restore the process of apoptosis.

Venclexta is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and commercialized by AbbVie outside of the U.S. Together, the companies are committed to research with Venclexta, which is currently being studied in clinical trials across several types of blood and other cancers.

In the U.S., Venclexta has been granted four Breakthrough Therapy Designations by the FDA: in combination with Rituxan for people with relapsed or refractory chronic lymphocytic leukemia (CLL); as a monotherapy for people with relapsed or refractory CLL with 17p deletion; in combination with hypomethylating agents (azacitidine or decitabine) for people with untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy; and in combination with low-dose cytarabine for people with untreated AML ineligible for intensive chemotherapy.

Venclexta Indications

Venclexta is a prescription medicine used:

To treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, who have received at least 1 prior treatment.
In combination with azacitidine, or decitabine, or low-dose cytarabine to treat adults with newly-diagnosed acute myeloid leukemia (AML) who:
‒ Are 75 years of age or older, or

‒ Have other medical conditions that prevent the use of standard chemotherapy.

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

Important Safety Information

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. The patient’s doctor will do tests to check their risk of getting TLS before they start taking Venclexta. The patient will receive other medicines before starting and during treatment with Venclexta to help reduce the risk of TLS. The patient may also need to receive intravenous (IV) fluids through their vein.

The patient’s doctor will do blood tests to check for TLS when the patient first starts treatment and during treatment with Venclexta. It is important for patients to keep appointments for blood tests. Patients should tell their doctor right away if they 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.

Patients should drink plenty of water during treatment with Venclexta to help reduce the risk of getting TLS.

Patients should drink 6 to 8 glasses (about 56 ounces total) of water each day, starting 2 days before the first dose, on the day of the first dose of Venclexta, and each time a dose is increased.

The patient’s doctor may delay, decrease the dose, or stop treatment with Venclexta if the patient has side effects.

Certain medicines must not be taken when the patient first starts taking Venclexta and while the dose is being slowly increased because of the risk of increased tumor lysis syndrome.

Patients must tell their doctor about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Venclexta and other medicines may affect each other, causing serious side effects.
Patients must not start new medicines during treatment with Venclexta without first talking with their doctor.
Before taking Venclexta, patients must tell their doctor about all of their medical conditions, including if they:

Have kidney problems.
Have problems with body salts or electrolytes, such as potassium, phosphorus, or calcium.
Have a history of high uric acid levels in the blood or gout.
Are scheduled to receive a vaccine. The patient should not receive a "live vaccine" before, during, or after treatment with Venclexta, until the patient’s doctor tells them it is okay. If the patient is not sure about the type of immunization or vaccine, the patient should ask their 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 an unborn baby. If the patient is able to become pregnant, the patient’s doctor should do a pregnancy test before the patient starts treatment with Venclexta, and the patient should use effective birth control during treatment and for at least 30 days after the last dose of Venclexta. If the patient becomes pregnant or thinks they are pregnant, the patient should tell their doctor right away.
Are breastfeeding or plan to breastfeed. It is not known if Venclexta passes into the patient’s breast milk. Patients should not breastfeed during treatment with Venclexta.
What to avoid while taking Venclexta:

Patients should not drink grapefruit juice, eat grapefruit, Seville oranges (often used in marmalades), or starfruit while they are taking Venclexta. These products may increase the amount of Venclexta in the patient’s blood.

Venclexta can cause serious side effects, including:

Low white blood cell counts (neutropenia). Low white blood cell counts are common with Venclexta, but can also be severe. The patient’s doctor will do blood tests to check their blood counts during treatment with Venclexta. Patients should tell their doctor right away if they have a fever or any signs of an infection during treatment with Venclexta.
The most common side effects of Venclexta when used in combination with rituximab in people with CLL include low white blood cell counts; diarrhea; upper respiratory tract infection; cough; tiredness; and nausea.

The most common side effects of Venclexta when used alone in people with CLL/SLL include low white blood cell counts; diarrhea; nausea; upper respiratory tract infection; low red blood cell counts; tiredness; low platelet counts; muscle and joint pain; swelling of arms, legs, hands, and feet; and cough.

The most common side effects of Venclexta in combination with azacitidine, or decitabine, or low-dose cytarabine in people with AML include low white blood cell counts; nausea; diarrhea; low platelet counts; constipation; fever with low white blood cell counts; low red blood cell counts; infection in blood; rash; dizziness; low blood pressure; fever; swelling of arms, legs, hands, and feet; vomiting; tiredness; shortness of breath; bleeding; infection in lung; stomach (abdominal) pain; pain in muscles or back; cough; and sore throat.

Venclexta may cause fertility problems in males. This may affect the ability to father a child. Patients should talk to their doctor if they have concerns about fertility.

These are not all the possible side effects of Venclexta. Patients should tell their doctor about any side effect that bothers them or that does not go away.

Report side effects to the FDA at 1-800-FDA-1088 or View Source Report side effects to Genentech at 1-888-835-2555.

Please visit View Source for the Venclexta full Prescribing Information, including Patient Information, for additional Important Safety Information.

Rituxan Indications

Rituxan (rituximab) injection, for intravenous use, is indicated for the treatment of:

Low-grade or follicular CD20-positive non-Hodgkin’s lymphoma as a single-agent therapy in patients whose disease recurred or did not respond to initial treatment
Follicular CD20-positive non-Hodgkin’s lymphoma as an initial treatment with chemotherapy, and in patients whose initial treatment was successful, as a single-agent follow-up therapy
Low-grade CD20-positive non-Hodgkin’s lymphoma as a single-agent follow-up therapy for patients who did not progress on initial treatment with CVP chemotherapy
CD20-positive diffuse large B-cell non-Hodgkin’s lymphoma as an initial treatment in combination with CHOP chemotherapy
CD20-positive chronic lymphocytic leukemia in combination with FC chemotherapy as an initial treatment or as a treatment after disease has recurred
It is not known if Rituxan is safe and effective in children.

Important Safety Information:

Rituxan can cause serious side effects that can lead to death, including:

Infusion Reactions: Infusion reactions are very common side effects of Rituxan treatment. Serious infusion reactions can happen during the patient’s infusion or within 24 hours after the patient’s infusion of Rituxan. The patient’s doctor should give the patient medicines before infusion of Rituxan to decrease the chance of having a severe infusion reaction.

Patients must tell their doctor or get medical help right away about any of these symptoms during or after an infusion of Rituxan:
Hives (red itchy welts) or rash
Itching
Swelling of the lips, tongue, throat, or face
Sudden cough
Shortness of breath, difficulty breathing, or wheezing
Weakness
Dizziness or feel faint
Palpitations (feel like the heart is racing or fluttering)
Chest pain
Severe Skin and Mouth Reactions: Patients must tell their doctor or get medical help right away about any of these symptoms at any time during treatment with Rituxan:
Painful sores or ulcers on the skin, lips, or in the mouth
Blisters
Peeling skin
Rash
Pustules
Hepatitis B Virus (HBV) Reactivation: Before receiving Rituxan treatment, the patient’s doctor will do blood tests to check for HBV infection. If the patient has had hepatitis B or is a carrier of hepatitis B virus, receiving Rituxan could cause the virus to become an active infection again. Hepatitis B reactivation may cause serious liver problems, including liver failure, and death. The patient’s doctor will monitor for hepatitis B infection during and for several months after the patient stops receiving Rituxan.

Patients must tell their doctor right away about worsening tiredness, or yellowing of the skin or white part of the eyes during treatment with Rituxan.
Progressive Multifocal Leukoencephalopathy (PML): PML is a rare, serious brain infection caused by a virus that can happen in people who receive Rituxan. People with weakened immune systems can get PML. PML can result in death or severe disability. There is no known treatment, prevention, or cure for PML.

Patients must tell their doctor right away about new or worsening symptoms or if anyone close to the patient notices these symptoms:
Confusion
Dizziness or loss of balance
Difficulty walking or talking
Decreased strength or weakness on one side of the body
Vision problems, such as blurred vision or loss of vision
What should patients tell their doctor before receiving Rituxan?

Before receiving Rituxan, patients should tell their doctor if they:

Have had a severe reaction to Rituxan or a rituximab product
Have a history of heart problems, irregular heartbeat, or chest pain
Have lung or kidney problems
Have had an infection, currently have an infection, or have a weakened immune system
Have or have had any severe infections including:
Hepatitis B virus (HBV)
Hepatitis C virus (HCV)
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)
Parvovirus B19
Varicella zoster virus (chickenpox or shingles)
West Nile Virus
Have had a recent vaccination or are scheduled to receive vaccinations. Patients should not receive certain vaccines before or during treatment with Rituxan
Have any other medical conditions
Are pregnant or plan to become pregnant. Patients must talk to their doctor about the risks to the patient’s unborn baby if receiving Rituxan during pregnancy. Females who are able to become pregnant should use effective birth control (contraception) during treatment with Rituxan and for 12 months after the last dose of Rituxan. Patients should talk to their doctor about effective birth control. Patients should tell their doctor right away if they become pregnant or think that they are pregnant during treatment with Rituxan
Are breastfeeding or plan to breastfeed. It is not known if Rituxan passes into the breast milk. Do not breastfeed during treatment and for at least 6 months after the last dose of Rituxan
Are taking any medications, including prescription and over-the-counter medicines, vitamins, and herbal supplements
What are the possible side effects of Rituxan?

Rituxan can cause serious side effects, including:

Tumor Lysis Syndrome (TLS): TLS is caused by the fast breakdown of cancer cells. TLS can cause the patient to have:
Kidney failure and the need for dialysis treatment
Abnormal heart rhythm
TLS can happen within 12 to 24 hours after an infusion of Rituxan. The patient’s doctor may do blood tests to check for TLS. The patient’s doctor may give medicine to help prevent TLS. Patients must tell their doctor right away if they have any of the following signs or symptoms of TLS:
Nausea
Vomiting
Diarrhea
Lack of energy
Serious Infections: Serious infections can happen during and after treatment with Rituxan, and can lead to death. Rituxan can increase the patient’s risk of getting infections and can lower the ability of the patient’s immune system to fight infections. Types of serious infections that can happen with Rituxan include bacterial, fungal, and viral infections. After receiving Rituxan, some people have developed low levels of certain antibodies in their blood for a long period of time (longer than 11 months). Some of these patients with low antibody levels developed infections. People with serious infections should not receive Rituxan. Patients must tell their doctor right away if they have any symptoms of infection:
Fever
Cold symptoms, such as runny nose or sore throat that do not go away
Flu symptoms, such as cough, tiredness, and body aches
Earache or headache
Pain during urination
Cold sores in the mouth or throat
Cuts, scrapes, or incisions that are red, warm, swollen, or painful
Heart Problems: Rituxan may cause chest pain, irregular heartbeats, and heart attack. The patient’s doctor may monitor the patient’s heart during and after treatment with Rituxan if they have symptoms of heart problems or have a history of heart problems. Patients must tell their doctor right away if they have chest pain or irregular heart-beats during treatment with Rituxan.
Kidney Problems: especially if the patient is receiving Rituxan for non-Hodgkin’s lymphoma. Rituxan can cause severe kidney problems that lead to death. The patient’s doctor should do blood tests to check how well their kidneys are working.
Stomach and Serious Bowel Problems That Can Sometimes Lead to Death: Bowel problems, including blockage or tears in the bowel can happen if the patient receives Rituxan with chemotherapy medicines. Patients must tell their doctor right away if they have any stomach-area (abdomen) pain or repeated vomiting during treatment with Rituxan.
The patient’s doctor will stop treatment with Rituxan if they have severe, serious, or life-threatening side effects.

What are the most common side effects during treatment with Rituxan?

Infusion-related reactions
Infections (may include fever, chills)
Body aches
Tiredness
Nausea
Other side effects include:

Aching joints during or within hours of receiving an infusion
More frequent upper respiratory tract infections
These are not all of the possible side effects with Rituxan.

Please see the Rituxan full Prescribing Information, including the Medication Guide, for additional Important Safety Information at www.Rituxan.com.

On December 3, 2018 Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today data from the primary analysis of the Phase III HAVEN 2 study evaluating Hemlibra (emicizumab-kxwh) prophylaxis in children younger than 12 years of age with hemophilia A with factor VIII inhibitors, including longer follow-up for once-weekly dosing and new data for less frequent dosing schedules (every two weeks or every four weeks) (Press release, Genentech, DEC 3, 2018, View Source [SID1234531845]). These data from the largest pivotal study in children with hemophilia A with factor VIII inhibitors were presented at the 60th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

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"Children with inhibitors are at increased risk of life-threatening bleeds and may experience frequent, repeated bleeding into joints," said Guy Young, M.D., director of Hemostasis and Thrombosis Center, Children’s Hospital Los Angeles, and professor of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, California. "These updated data from HAVEN 2 showed that the majority of children with hemophilia A with factor VIII inhibitors treated with emicizumab-kxwh had zero treated bleeds across three different dosing schedules, reinforcing the ability of this medicine to provide sustained, effective bleed control."

In updated results from the HAVEN 2 study with a median of 11 additional months of data, 76.9 percent (95 percent CI: 64.8; 86.5) of children with hemophilia A with factor VIII inhibitors treated with Hemlibra once weekly (n=65) experienced zero treated bleeds. Importantly, once-weekly Hemlibra showed a 99 percent (95 percent CI: 97.7; 99.4) reduction in treated bleeds compared to prior treatment with bypassing agents (BPAs) as prophylaxis (n=15) or on-demand (n=3) in a prospective intra-patient comparison. New data also showed that 90 percent (95 percent CI: 55.5; 99.7) of children with factor VIII inhibitors receiving Hemlibra every two weeks (n=10) and 60 percent (95 percent CI: 26.2; 87.8) of children receiving Hemlibra every four weeks (n=10) experienced zero treated bleeds, demonstrating clinically meaningful bleed control at both dosing schedules. No cases of thrombotic microangiopathy (TMA) or thrombotic events occurred. The most common adverse events (AEs) in the HAVEN 2 study primary analysis were consistent with those previously observed in the interim analyses.

"The updated analysis from the HAVEN 2 study supports the potential of Hemlibra to control bleeds at less frequent subcutaneous dosing, providing parents and their children more flexibility to choose a treatment schedule that is right for them," said Sandra Horning, M.D., chief medical officer and head of Global Product Development. "Many children with hemophilia A with factor VIII inhibitors have already experienced the benefits of Hemlibra, and with these new positive data, we are confident that this treatment will continue to make a meaningful difference in their lives."

Hemlibra is approved in over 50 countries worldwide, including the U.S., EU member states and Japan, to treat people of all ages with hemophilia A with factor VIII inhibitors based on pivotal data that included interim results from the HAVEN 2 study. In October 2018, the U.S. Food and Drug Administration (FDA) also approved Hemlibra to treat people of all ages with hemophilia A without factor VIII inhibitors. Hemlibra is the only FDA-approved treatment for people with hemophilia A with and without factor VIII inhibitors that can be administered subcutaneously (under the skin) and at multiple dosing options (once weekly, every two weeks or every four weeks). Submissions to other regulatory authorities around the world are ongoing.

Hemlibra has been studied in one of the largest pivotal clinical trial programs in people with hemophilia A with and without factor VIII inhibitors, including four Phase III HAVEN studies (HAVEN 1, HAVEN 2, HAVEN 3 and HAVEN 4).

About HAVEN 2 (NCT02795767)

HAVEN 2 is a multicenter, open-label, clinical study in children younger than 12 years of age with hemophilia A with factor VIII inhibitors. The study is evaluating the efficacy, safety and pharmacokinetics of once-weekly, every two weeks or every four weeks subcutaneous administration of Hemlibra prophylaxis.

The HAVEN 2 primary analysis included 85 children (once-weekly dosing, n=65; every two week dosing, n=10; every four week dosing, n=10) with hemophilia A with factor VIII inhibitors. The median follow-up period for each cohort was 58 (range 17.9–92.6), 21.3 (range 18.6–24.1), and 19.9 (range 8.9–24.1) weeks, respectively. The prospective intra-patient comparison included 18 patients from the once-weekly cohort previously treated with BPAs either as prophylaxis (n=15) or on-demand (n=3) as part of a non-interventional study.

The study met its primary endpoint and key secondary endpoints. Data presented at the 60th ASH (Free ASH Whitepaper) Annual Meeting showed:

HAVEN 2 (NCT02795767)
Hemlibra prophylaxis 1.5 mg/kg QW
(Arm A; n=65)*

Annualized bleeding rate [ABR] †
(95% CI)

Median ABR
(Interquartile range; IQR)

Treated bleeds (primary endpoint)**
0.3
(0.17; 0.50)

0.0
(0.00; 0.00)

All bleeds
3.2
(1.94; 5.22)

0.6
(0.00; 2.92)

Treated spontaneous bleeds
0.0
(0.01; 0.10)

0.0
(0.00; 0.00)

Treated joint bleeds
0.2
(0.08; 0.29)

0.0
(0.00; 0.00)

Treated target joint bleeds
Not estimable

0.0
(0.00; 0.00)

*Efficacy assessment was conducted only in patients aged <12 years who had spent at least 12 weeks on the study. Excludes three patients aged >12 years.

A loading dose of 3 mg/kg Hemlibra was given for four weeks followed by the maintenance dose listed.

† Estimated using negative binomial regression

**In patients receiving Hemlibra once weekly (Arm A), 76.9% (95% CI, 64.8; 86.5) experienced zero treated bleeds and 23.1% experienced 1–3 treated bleeds.

Hemlibra prophylaxis 3 mg/kg
Q2W
(Arm B; n=10)*

Hemlibra prophylaxis 6 mg/kg
Q4W
(Arm C; n=10)*

ABR (95% CI) †

0.2
(0.03; 1.72)

2.2
(0.69; 6.81)

Median ABR (IQR)
0.0
(0.00; 0.00)

0.0
(0.00; 3.26)

% patients with zero treated
bleeds
(95% CI)

90.0%
(55.5; 99.7)

60.0%
(26.2; 87.8)

% patients with 1-3 treated
bleeds
(95% CI)

10.0%
(0.3; 44.5)

40.0%
(12.2; 73.8)

*A loading dose of 3 mg/kg Hemlibra was given for four weeks followed by the maintenance dose listed.

† Estimated using negative binomial regression

The most common adverse reactions occurring in 10 percent or more of children treated with Hemlibra were common cold symptoms (nasopharyngitis; 37.5 percent), injection site reactions (29.5 percent), fever (pyrexia; 23.9 percent), upper respiratory tract infection (23.9 percent), cough (23.9 percent), diarrhea (15.9 percent), vomiting (15.9 percent), headache (14.8 percent), contusion (12.5 percent), fall (12.5 percent) and influenza (10.2 percent). No cases of TMA or thrombotic events occurred. Four patients tested positive for anti-drug antibodies (ADAs) to Hemlibra. Of these patients, two had ADAs with neutralizing potential based on reduced Hemlibra levels. As previously reported, the ADA in one of these patients resulted in reduced efficacy of Hemlibra and led to discontinuation of treatment. The other patient had no bleeds as of the clinical cut-off date of the study.

About Hemlibra

Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for hemophilia A patients. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly, every two weeks or every four weeks. Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed globally by Chugai, Roche and Genentech.

Hemlibra U.S. Indication

Hemlibra is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A with or without factor VIII inhibitors.

Important Safety Information

What is the most important information to know about Hemlibra?

Hemlibra increases the potential for blood to clot. Patients should carefully follow their healthcare provider’s instructions regarding when to use an on-demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. Hemlibra may cause the following serious side effects when used with activated prothrombin complex concentrate (aPCC; FEIBA), including:

Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to one’s kidneys, brain, and other organs. Patients should get medical help right away if they have any of the following signs or symptoms during or after treatment with Hemlibra:
confusion
weakness
swelling of arms and legs
yellowing of skin and eyes
stomach (abdomen) or back pain
nausea or vomiting
feeling sick
decreased urination
Blood clots (thrombotic events). Blood clots may form in blood vessels in the arm, leg, lung, or head. Patients should get medical help right away if they have any of these signs or symptoms of blood clots during or after treatment with Hemlibra:
swelling in arms or legs
pain or redness in the arms or legs
shortness of breath
chest pain or tightness
fast heart rate
cough up blood
feel faint
headache
numbness in the face
eye pain or swelling
trouble seeing
If aPCC (FEIBA) is needed, patients should talk to their healthcare provider in case they feel they need more than 100 U/kg of aPCC (FEIBA) total.

Before using Hemlibra, patients should tell their healthcare provider about all of their medical conditions, including if they:

are pregnant or plan to become pregnant. It is not known if Hemlibra may harm an unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with Hemlibra.
are breastfeeding or plan to breastfeed. It is not known if Hemlibra passes into breast milk.
Patients should tell their healthcare provider about all the medicines they take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Patients should keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.

How should patients use Hemlibra?

Patients should see the detailed "Instructions for Use" that comes with Hemlibra for information on how to prepare and inject a dose of Hemlibra, and how to properly throw away (dispose of) used needles and syringes.

Stop (discontinue) prophylactic use of bypassing agents the day before starting Hemlibra prophylaxis.
Patients may continue prophylactic use of factor VIII for the first week of Hemlibra prophylaxis.
What should patients know about lab monitoring?

Hemlibra may interfere with laboratory tests that measure how well blood is clotting and may cause a false reading. Patients should talk to their healthcare provider about how this may affect their care.

The most common side effects of Hemlibra include: redness, tenderness, warmth, or itching at the site of injection; headache; and joint pain.

These are not all of the possible side effects of Hemlibra. Patients should speak to their healthcare provider for medical advice about side effects.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Patients should not use Hemlibra for a condition for which it was not prescribed. Patients should not give Hemlibra to other people, even if they have the same symptoms that they have. It may harm them. Patients can ask their pharmacist or healthcare provider for information about Hemlibra that is written for health professionals.

Side effects may be reported to the FDA at (800) FDA-1088 or View Source Side effects may also be reported to Genentech at (888) 835-2555.

Please see the Hemlibra full Prescribing Information and Medication Guide for more important safety information including Serious Side Effects.

About hemophilia A

Hemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia affects around 20,000 people in the United States, with hemophilia A being the most common form and approximately 50-60 percent of people living with a severe form of the disorder.

People with hemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. Depending on the severity of their disorder, people with hemophilia A can bleed frequently, especially into their joints or muscles. These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility and long-term joint damage.

A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding.

On December 3, 2018 TRIGR Therapeutics, Inc. ("TRIGR"), and ABL Bio, Inc. ("ABL"), reported that they have entered into a collaboration and license agreement for TR009 (formerly known as ABL001 or NOV1501), an ABL developed bispecific antibody candidate targeting two important angiogenic factors, VEGF and DLL4 (Press release, TRIGR Therapeutics, DEC 3, 2018, View Source [SID1234531844]). The license agreement is exclusive and global, excluding the Republic of Korea for all oncology indications and excluding the Republic of Korea and Japan for all ophthalmology indications. This agreement is in addition to the recently announced agreement whereby TRIGR licensed pre-clinical immune engaging bispecific antibodies from ABL.

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TR009 is currently in a dose escalation Phase 1a study being conducted at the Samsung Medical Center in South Korea. The phase 1a study is sponsored by ABL and National OncoVenture (NOV), a South Korean government funded oncology drug development program. A phase 1b study looking to combine TR009 with chemotherapy and a checkpoint inhibitor is expected to commence in the latter part of 2019.

To date, 12 patients have been dosed with TR009 and no dose-limiting toxicities (DLTs) have been reported. Based on preliminary patient data, TR009 single agent clinical activity has been demonstrated across all dose levels among heavily pre-treated (5+ lines of prior therapy) cancer patients with solid tumors including gastric, colon, GIST, and ovarian cancers. At the mid-dose level cohort, more than half of the patients have experienced durable clinical benefit in terms of tumor stabilization (stable disease).

Under the terms of the agreement, TRIGR is responsible for global Phase 2 and subsequent clinical development and commercialization activities for TR009 for all oncology indications. ABL will receive an upfront payment of $5 million and is eligible to receive up to $405 million in regulatory and sales milestones and royalties on oncology sales of TR009 outside of the Republic of Korea. For ophthalmology indications, TRIGR is responsible for all development and commercialization within its territories. ABL is eligible to receive up to $185 million in milestone payments and royalties on TR009 ophthalmology sales outside of the Republic of Korea and Japan.

"We are delighted to expand our relationship with ABL," said George Uy, CEO of TRIGR. "Combining both companies’ core competencies and resources will optimize our chances of success in developing this novel cancer therapy. ABL has an outstanding track record of bispecific antibody research and development with extensive capabilities in antibody engineering and validation. We are excited by the promising clinical activity that TR009 has shown thus far, especially in heavily pre-treated patients with gastric and colon cancers, which is a key differentiator of this program. Based on our pre-clinical validation and additional biomarker work, our short-term strategy for TR009 is to pursue an accelerated approval pathway in Asia and we intend to approach both Chinese (NMPA) and Japanese regulators upon completion of our Phase 1a study in mid-2019. We also plan to simultaneously seek regulatory guidance from the FDA and EMEA for the registration of TR009 in solid tumor patients in the US and Europe."

"We are very pleased to enter into this agreement with our partners at TRIGR, a premier team that is highly experienced in taking anti-cancer drugs through clinical development and commercialization," said Sang Hoon Lee, CEO of ABL. "The dual VEGF/DLL4 bispecific antibodies currently in clinical development have all shown meaningful clinical activity even in patients who have failed or progressed on multiple lines of prior chemotherapy and VEGF-directed therapies such as Avastin and Cyramza. Across all trials, over 140 patients have been treated in monotherapy or in combination settings and we are seeing clinical benefit rates of between 50-85%. This is clearly exciting news for cancer patients worldwide."

Anti-angiogenic therapy is a cornerstone in cancer care, with sales of Avastin (an anti-VEGF antibody, Roche) and Cymraza (an anti-VEGF-R2 antibody, Eli Lilly) comprising approximately $7.5 billion in 2017. Although this class of drugs has proven survival benefits, resistance is creating the need for alternative regimens. Dual blockade of both VEFG and DLL4 is emerging as the next frontier of angiogenic therapy as the combination of these 2 mechanisms has been shown to overcome VEGF inhibitor resistance. There are 3 programs currently in clinical development targeting anti-VEGF/DLL4: AbbVie’s ABT-165 (Nasdaq: ABBV) which has recently entered Phase 2 in colorectal cancer, Oncomed’s OMP305B83 (Nasdaq: OMED) in Phase 1b in platinum-resistant ovarian cancer, and TRIGR’s TR009 in Phase 1a.

On December 3, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported its the long-term results of the Phase 3 ALCYONE study demonstrating that the addition of Darzalex (daratumumab) to bortezomib , melphalan and prednisone (VMP) continued to show significant improvement in progression-free survival (PFS) in patients recently diagnosed with multiple myeloma who are ineligible for autologous stem cell transplantation (GATS) (Press release, Johnson & Johnson, DEC 3, 2018, View Source [SID1234531843]). 1 These data ( Summary No. 156 ), as well as the updates of the LYRA ( Summary No. 152 ) and GRIFFIN ( Summary No. 151)) Phase 2 in patients with multiple myeloma were presented in an oral session on data presentation abstracts at the 60 th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) that was held in San Diego, California.

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Long-term results of the ALCYONE Phase 3 trial for first-line combined treatment with daratumumab 1

With a median follow-up of 27.8 months, the results of the study showed that the addition of daratumumab to the combination of bortezomib, melphalan and prednisone (VMP) reduced the risk of disease progression by 57 percent. or death, in comparison with treatment based solely on the VMP combination (risk ratio [RR] = 0.43, 95 percent confidence interval [CI] 0.35-0.54, p <0, 0001). 1 The combination of daratumumab-VMP resulted in a 24-month PHC rate of 63 percent, compared to 36 percent for VMP alone. 1 The median PFS for the combination of araratumumab-VMP has not yet been reached, and the control group (PMV alone) had a median PFS of 19.1 months.1 In addition, a significantly higher overall response rate (91 percent vs. 74 percent, respectively) was observed for the combination based on daratumumab, compared with the single VMP. 1 The combination of daratumumab-VMP achieved faster responses, with a significant improvement in the rate of very good partial response or higher rate (73 percent versus 50 percent), and a strict complete response rate more than twice as high ( 22 percent vs. 8 percent) to that of the VMP alone. 1 The combination of aratumumab-VMP induced a higher rate of long-term residual residual disease negativity compared to VMP alone (10 percent versus 2 percent, respectively).1 The main results previously announced in this study motivated the European Commission to approve daratumumab in combination with MPV for patients with newly diagnosed multiple myeloma who are not eligible for GATS.

Long-term data from pivotal ALCYONE trial show that combined treatment with daratumumab continued to demonstrate improved progression-free survival and response rates in newly diagnosed patients with multiple myeloma, including patients older people less likely to respond to treatment, "said Meletios A. Dimopoulos, MD, professor and chair of the Clinical Therapies Department at the Faculty of Medicine at the National Capodistrian University of Athens, Greece, and principal investigator. These promising results support the use of daratumumab earlier in the treatment paradigm,

In the ALCYONE study, the most common grade 3/4 adverse events that occurred during treatment with daratumumab-VMP starting in cycle 10 included anemia (4 percent), neutropenia (2 percent), and bronchitis (1 percent). 1 No new safety concerns were observed, and Grade 3/4 infections remained treatable. 1

Data from LYRA and GRIFFIN Phase 2 trials support the efficacy and safety profile of daratumumab in newly diagnosed patients, including those who are eligible for high-dose treatment / GATS, and in patients in relapse 2 , 3

Response rates from the LYRA Phase 2 study were presented for the experimental use of daratumumab plus cyclophosphamide, bortezomib, and dexamethasone (CyBorD) in patients recently diagnosed with multiple and relapsed myeloma. 2 The overall response rate and TBRP or upper rate in 86 newly diagnosed patients, who were 79 and 44 percent, respectively, after 4 cycles, increased to 81 and 56 percent, respectively, at the end of the initial treatment period (average of 6 cycles). 2In addition, the TBRP or higher rate in 14 patients with recurrent multiple myeloma, which was 57 percent after 4 cycles, then increased to 64 percent at the end of induction, while the rate overall response remained stable at 71 percent (average of 7.5 cycles). 2 The 18-month PHC rate was 78 percent in newly diagnosed and ineligible autologous patients, compared with 53 percent in relapsed patients. 2 In addition, this study, which evaluated the fractionation of the first dose of daratumumab to reduce infusion duration on Day 1 of Cycle 1 (C1D1), demonstrated a safety profile consistent with previous studies. . 2Infusion reactions occurred in 49 percent of patients with C1D1, compared to four percent of patients on Day 2 of Cycle 1 (C1D2). Fifty-four percent of newly diagnosed patients experienced infusion reactions, the most common being: chills (14 percent), dyspnoea, pruritus, and nausea (8 percent each), as well as coughing. (7 percent). Fifty-seven percent of relapsed patients experienced infusion-related reactions, the most common of which were: cough (21 percent), hyperhidrosis, dyspnea and chills (7 percent each). Only two patients had a grade 3 infusion reaction, and no grade 4 infusion reaction occurred. has been noted. No interruption of taking daratumumab was necessary because of an infusion reaction. The median infusion time was 4.5 hours at C1D1, compared to 3.8 hours at C1D2.2 Grade 3/4 adverse events that occurred during treatment were reported in 56 percent of patients, the most common (≥10 percent) being neutropenia (13 percent). 2

Data presented in the GRIFFIN Phase 2 study evaluated daratumumab in combination with bortezomib, lenalidomide and dexamethasone (VRd) in a safety group of 16 patients recently diagnosed with multiple myeloma, eligible for high dose treatment and GATS. 3 The results showed that at the end of the GATS consolidation treatment, all patients who participated in the safety preparatory period achieved a TBRP or higher rate, and 63 percent of them achieved complete response (CR) or higher, with 25 percent of patients having achieved SCR. 3In addition, 94 percent of patients remained without progression during the study, at a median follow-up of 16.8 months. 3 In addition, 8 out of 16 patients (50 percent) were negative for the residual disease test, at a level of 10 -5 at the end of consolidation. 3 During grade 3/4 treatment, fourteen patients (88 percent) reported adverse events, including 10 cases (63 percent of patients) related to daratumumab treatment. 3The most common adverse events (≥10 per cent) that occurred during grade 3/4 treatment were neutropenia, pneumonia, thrombocytopenia, lymphopenia, febrile neutropenia, leukopenia, rash, and hypophosphatemia. 3 Thirteen patients (81 percent) had the following infections, all grades: upper respiratory infection (six patients), pneumonia (four patients), bronchitis (two patients), otitis and viral gastroenteritis (two patients each) ). 3 No deaths due to serious adverse events were reported and no patient had to discontinue treatment due to an adverse event. 3These data suggest that induction therapy with daratumumab has no negative impact on stem cell mobilization. All 16 patients had successful stem cell mobilization, followed by GATS. 3

"Daratumumab offers a consistent clinical benefit across multiple therapeutic lines for multiple myeloma, and positive data from the ALCYONE, LYRA, and GRIFFIN studies add to the solid body of evidence supporting daratumumab-based protocols," said Dr. Dr. Catherine Taylor, Head of Hematology Treatments for Europe, Middle East and Africa (EMEA) at Janssen-Cilag Limited. "These are important findings for patients that provide additional information about the most effective methods of managing care," she added.

#END#

About the ALCYONE 4 trial

The randomized, open-label, multi-center Phase 3 ALCYONE (MMY3007) study enrolled 706 patients newly diagnosed with multiple myeloma and ineligible for high-dose GSC chemotherapy. The median age of these patients was 71 years (age range: 40-93). Patients were randomized to receive nine cycles of daratumumab combined with VMP, or VMP alone. In the daratumumab-VMP group, patients received 16 mg / kg of daratumumab once a week for the first week (cycle 1) and then once every three weeks (cycles 2-9). After nine cycles, they continued to receive 16 mg / kg of daratumumab once every four weeks until disease progression.

About the LYRA 5 trial

The ongoing, single-arm, open-label, multi-center LYRA (MMY2012) Phase 2 study enrolled 100 adult patients 18 years of age and older. Patients received 4-8 cycles of combination therapy with daratumumab, including an oral dose of cyclophosphamide 300 mg / m 2 on days 1, 8, 15 and 22; a subcutaneous dose of bortezomib 1.5 mg / m 2 on days 1, 8 and 15; a weekly oral or intravenous dose of dexamethasone 40 mg every 28 days. Daratumumab was administered at 8 mg / kg intravenously at days 1 and 2 of cycle 1, at a weekly dose of 16 mg / kg from cycle 1, at day 8 during cycle 2, at a dose of 16 mg / kg every 2 weeks at cycles 3-6, and at a dose of 16 mg / kg every 4 weeks at cycles 7-8. After the induction treatment, the patients were able to receive a GATS. All patients received 12 cycles of maintenance treatment of 16 mg / kg intravenously every 4 weeks.

About the GRIFFIN 6 trial

The randomized, open-label Phase II GRIFFIN study (MMY2004) recruited and treated more than 200 adults between 18 and 70 years of age, eligible for high-dose treatment / GATS, 7including 16 patients in the safety preparatory phase to evaluate the potential dose limiting toxicities during cycle 1 of daratumumab combined with VRd. The latter patients were treated with four cycles of daratumumab and VRd infusion every 21 days, followed by stem cell mobilization, high-dose treatment and GATS; two consolidation cycles with daratumumab and VRd; as well as maintenance therapy with daratumumab and lenalidomide at cycles 7-32. During induction and consolidation therapy (cycles 1-6), patients received an oral dose of 25 mg lenalidomide on days 1-14, a dose of 1.3 mg / m 2bortezomib subcutaneously on days 1, 4, 8 and 11 and a dose of 20 mg dexamethasone on days 1, 2, 8, 9, 15 and 16 every 21 days. An infusion of daratumumab 16 mg / kg IV was administered on days 1, 8 and 15 of cycles 1-4 and day 1 of cycles 5-6. During the maintenance period (cycles 7-32), patients received a daily dose of 10 mg lenalidomide (15 mg from cycle 10, if tolerated) on days 1-21 every 28 days, and an injection of daratumumab 16 mg / kg every 56 days; this treatment was adjusted every 28 days. Lenalidomide maintenance therapy can be extended beyond cycle 32, according to the local care protocol.7

About Daratumumab

Daratumumab is an advanced biological product targeting the CD38 gene, a surface protein that is overexpressed in multiple multiple myeloma cells, regardless of the stage of the disease. 8 The Daratumumab induce the death of tumor cells via multiple mechanisms of action immunologically mediated, including complement-dependent cytotoxicity (CDC), an antibody-dependent cellular cytotoxicity (CBDC) and dependent cellular phagocytosis of antibody (PCDA) and via apoptosis, during which a series of molecular steps inside the cell leads to the death of the cell. 9A subset of suppressive cells derived from myeloid, CD38 + regulatory T cells and CD38 + B cells was reduced by daratumumab. 9 Daratumumab is being evaluated as part of a comprehensive clinical development program covering a range of treatment protocols for multiple myeloma, including first-line treatment, or recurrence. 10,11,12,13,14,15,16,17 Additional studies are underway or planned to evaluate the potential of this treatment targeting other malignant and pre-malignant haematological conditions in which the CD38 gene is expressed, such as indolent myeloma. 18,19For more information, please visit www.clinicaltrials.gov .

In Europe, daratumumab is indicated for use in combination with bortezomib, melphalan and prednisone for the treatment of newly diagnosed adult patients with multiple myeloma who are ineligible for autologous stem cell transplantation as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, previously treated with a proteasome inhibitor and an immunomodulatory agent, and who experienced disease progression during the last treatment, and in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, and for the treatment of adult patients with multiple myeloma who have benefited fromat least one prior treatment.9 For more information on daratumumab, please see the summary of product characteristics at View Source .

In August 2012 , Janssen Biotech, Inc. and Genmab A / S entered into a worldwide agreement granting Janssen an exclusive license to develop, manufacture and market daratumumab. 20

About multiple myeloma

Multiple myeloma is an incurable cancer of the blood that is found in the bone marrow. The disease is characterized by excessive proliferation of plasma cells. 21 More than 45,000 new cases of multiple myeloma were diagnosed in Europe in 2016, and more than 29,000 patients died. 22 Up to half of newly diagnosed patients do not achieve five-year survival, 23 and nearly 29% of multiple myeloma patients die within one year of diagnosis. 24

Although the treatment may lead to remission, in most cases a relapse will occur because no cure is currently possible. 25 A refractory multiple myeloma is characterized by the fact that the patient’s disease progresses within 60 days following the last treatment. 26,27 A recurrent cancer is characterized by the fact that the disease recurs after a period of initial, partial or complete remission. 28While some patients with multiple myeloma have absolutely no symptoms, the majority of them are diagnosed with symptoms that may include bone problems, low blood counts, increased calcium levels, infections or kidney problems. 29 Patients who have relapsed after treatment with standard therapy, including inhibitors of the proteasome and immunumodulateurs agents have poor prognosis and few treatment options. 30

On December 3, 2018 Amphivena Therapeutics, Inc., reported a privately held biotechnology company developing AMV564, a CD33/CD3 T cell engager for the treatment of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS), presented Saturday night in a poster presentation at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) first-in-human Phase 1 clinical data that demonstrate that in patients with relapsed/refractory AML, AMV564 is well-tolerated and has anti-leukemic activity through T-cell engagement (Press release, Amphivena Therapeutics, DEC 3, 2018, View Source [SID1234531842]). The data from this ongoing dose escalation trial further show that AMV564 has a unique PK profile with a gradual increase in drug exposures that mitigates cytokine release syndrome (CRS).

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"The ASH (Free ASH Whitepaper) data reports continued evidence of single-agent clinical activity in heavily pre-treated patients with refractory/relapsed AML. AMV564 has been well-tolerated and has the potential to be safely combined with other agents. Importantly, its 2-day half-life supports intermittent dosing which differentiates AMV564 from other T cell engagers in development for myeloid malignancies," said Eric J. Feldman, M.D., Amphivena’s Chief Medical Officer.

The poster highlights the safety and efficacy data on 26 evaluable patients, as follows:

Complete and partial responses (CRi, PR) observed in patients dosed at 100 mcg with a 14-day dosing regimen
No dose-limiting toxicity through the 150 mcg cohort, with a 0% 30-day mortality rate
No Grade 2+ CRS with a lead-in dose and no Grade 3+ CRS
Novel pharmacokinetic profile with a 2-day terminal half-life
A seamless Phase 1/2 study is ongoing at six centers in the U.S.