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 AOP Orphan Pharmaceuticals AG (AOP Orphan) reported latest follow-up results on Ropeginterferon alfa-2b in patients with Polycythemia Vera (PV) from CONTINUATION-PV presented at ASH (Free ASH Whitepaper) 2018 (Press release, AOP Orphan Pharmaceuticals, DEC 3, 2018, View Source [SID1234531862]).

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CONTINUATION-PV is an open-label, multicenter, phase IIIb study assessing the long-term efficacy and safety of Ropeginterferon alfa-2b versus hydroxyurea (HU) or best available treatment (BAT) in patients with PV who previously participated in the PROUD-PV study.

Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon (ATC L03AB15). It is administered once every 2 weeks initially, or monthly after stabilization of hematological parameters. It is expected to be the first interferon approved for PV worldwide. AOP Orphan´s submission for marketing authorization in the EU is in the final stage of EMA review.

Clinical evidence:

Previously, at 12 months of treatment, Ropeginterferon alfa-2b was shown to be non-inferior to hydroxyurea (HU) in Complete Hematologic Response (CHR) and to have a significantly better safety and tolerability profile. . At 24 months Ropeginterferon alfa-2b achieved a significantly higher CHR of 70.5% versus 49.3% compared with HU/BAT (p=0.0101).

After 36 months of treatment Ropeginterferon alfa-2b sustained higher CHR response rates compared to HU/BAT (70.5% vs. 51.4%; p=0.0122). Further, the composite endpoint, CHR including disease symptom improvement was higher in patients treated with Ropeginterferon alfa-2b compared to HU/BAT (52.6% vs. 37.8%; p=0.0437).

Disease modification evidence:


66.0% of PV patients treated with Ropeginterferon alfa-2b, but only 27.0% having received HU/BAT showed a mutant JAK2 molecular response (p<0.0001) after 36 months. Importantly, molecular response strongly correlated with CHR, emphasizing the clinical relevance of mutant JAK2 allele burden reduction.

Analysis of additional non-JAK2 mutations, which are believed to contribute to disease progression revealed that Ropeginterferon alfa-2b, but not HU was able to reduce their respective mutant allele burden. This suggests that only Ropeginterferon alfa-2b but not HU has the ability to suppress additional clones with different mutations and modify the disease at the molecular level.

In line with molecular findings, disease or treatment related secondary malignancies occurred only in patients receiving HU/BAT, including 2 cases of acute myeloid leukemia, 1 melanoma and 2 basaliomas, whereas 3 malignancies (glioblastoma, seminoma, adrenal neoplasm) most likely unrelated to treatment were reported for patients treated with Ropeginterferon alfa-2b.

A similar number of patients experienced adverse events (89.8% for Ropeginterferon alfa-2b, 90.6% for HU) and treatment-related adverse events (74.8% for Ropeginterferon alfa-2b, 78.7% for HU). The most common (>10%) treatment-related adverse events anemia, thrombocytopenia and leukopenia occurred more frequently with HU, whereas liver enzyme increase was mainly observed with Ropeginterferon alfa-2b.

No new safety signals appeared in the third year of treatment.

Professor Heinz Gisslinger from the Medical University of Vienna, Austria presenting the results at ASH (Free ASH Whitepaper) stated, "The observed superior efficacy of Ropeginterferon alfa-2b over hydroxyurea/best-available-therapy after 36 months, is a clear proof of the long-term value of this treatment modality. Thus, Ropeginterferon alfa-2b will provide a valuable and safe new first line therapy for PV patients".

Professor Jean-Jacques Kiladjian from the Saint-Louis Hospital & Paris Diderot University in France, concluded, "The disease modification capability of Ropeginterferon alfa-2b suggested by a significant reduction of not only mutant JAK2, but also non-JAK2 allele burden and the specific targeting of the malignant clone, holds promise for improvement of progression-free survival and long-term patient benefit."

About Ropeginterferon alfa-2b


Ropeginterferon alfa-2b is a novel, long-acting, mono-pegylated proline interferon (ATC L03AB15) with improved pharmacokinetic properties offering improved tolerability and convenience. It is administered once every 2 weeks, or monthly during long-term maintenance, and is expected to be the first interferon approved for PV worldwide. AOP Orphan´s submission for marketing authorization in the EU is currently under EMA review.

Ropeginterferon alfa-2b was discovered by PharmaEssentia, a long-term partner of AOP Orphan. Ropeginterferon alfa-2b has Orphan Drug designation in the European Union, Switzerland and the United States of America.


In 2009, AOP Orphan has in-licensed from PharmaEssentia Corporation the exclusive rights to develop and commercialize Ropeginterferon alfa-2b in PV, other MPNs and CML for European, Commonwealth of Independent States (CIS), and Middle Eastern markets.

About Polycythemia Vera


Polycythemia Vera (PV) is a cancer of the blood-building cells in the bone marrow resulting in a chronic increase of red blood cells, white blood cells and platelets. This condition may result in circulatory disorders such as thrombosis and embolism, as well as malignant transformation to myelofibrosis or leukemia. While the molecular mechanism underlying PV is still subject of intense research, current results point to a set of acquired mutations, the most important being a mutant form of JAK2 that make the malignant clone.

On December 3, 2018 Progenics Pharmaceuticals, Inc. (NASDAQ:PGNX), an oncology company developing innovative medicines and imaging analysis technology for targeting and treating cancer, reported that the first patient has been dosed in the Company’s Phase 3 CONDOR study evaluating the diagnostic performance and clinical impact of PyL (18F-DCFPyL) in men with biochemical recurrence of prostate cancer (Press release, Progenics Pharmaceuticals, DEC 3, 2018, View Source [SID1234531895]). PyL is the Company’s PSMA-targeted small molecule PET/CT imaging agent designed to visualize prostate cancer.

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Dr. Lawrence Saperstein, Assistant Professor of Radiology and Biomedical Imaging and Chief of Nuclear Medicine at Yale Smilow Cancer Hospital, and a principle investigator of the trial said, "PyL has demonstrated excellent positive and negative predictive values in detecting the presence or absence of prostate cancer. This valuable information has the potential to provide earlier diagnoses, more informed treatment decisions, the ability to monitor responses, and ultimately improve patient outcomes."

The Phase 3 CONDOR trial is a multi-center, open label study and will enroll approximately 200 patients with biochemical recurrence of prostate cancer in 14 sites in the United States and Canada. The primary endpoint is based on positive predictive value and will assess the correct localization rate (CLR), defined as a percentage of subjects with a one-to-one correspondence between localization of at least one lesion identified by PyL and the composite truth standard. Secondary measures include the percentage of subjects with a change in intended prostate cancer treatment plans due to PyL PET/CT imaging.

"The initiation of this landmark trial marks an important milestone in the development of PSMA-targeted imaging agents which have the potential to transform the treatment landscape for recurrent prostate cancer," stated Mark Baker, CEO of Progenics. "With PyL, physicians may be able to detect very small lesions that are currently missed with conventional imaging methods, which in turn could change the treatment path. We look forward to reporting data from this trial in early 2020."

Progenics Initiates Phase 3 Trial of PyL PSMA PET Imaging Agent Page 2

In prior studies, PyL has shown strong positive predictive value to detect prostate cancer, with high sensitivity (93-99%) in reliably detecting metastatic prostate cancer lesions and high specificity (96-99%) in confirming the absence of pelvic lymph node disease.

About PyL for PET Imaging of Prostate Cancer

PyL (also known as [18F]DCFPyL) is a fluorinated PSMA-targeted Positron Emission Topography ("PET") imaging agent that enables visualization of both bone and soft tissue metastases to determine the presence or absence of recurrent and/or metastatic prostate cancer.

About Prostate Cancer

Prostate cancer is the second most common form of cancer affecting men in the United States: an estimated one in seven men will be diagnosed with prostate cancer in his lifetime. The American Cancer Society estimates that each year approximately 164,690 new cases of prostate cancer will be diagnosed and about 29,430 men will die of the disease. Approximately 2.9 million men in the U.S. currently count themselves among prostate cancer survivors

On December 2, 2018 Novartis reported its results of a retrospective, real-world evidence study in patients with immune thrombocytopenia (ITP) treated with Revolade (eltrombopag), compared to other second-line therapies (Press release, Novartis, DEC 2, 2018, View Source [SID1234531762]). The data demonstrated that patients experienced better clinical outcomes with Revolade, in terms of fewer bleeding episodes. The data were presented during the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in San Diego.

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"Despite advances in treating immune thrombocytopenia, many patients remain at risk for bleeding episodes," said Samit Hirawat, MD, Head, Novartis Oncology Global Drug Development. "With these kind of real-world data, we can reimagine care by more clearly understanding the outcomes of a range of treatments and, in turn, helping healthcare providers better navigate available options with their patients."

Electronic health records (EHR) data from January 1, 2009 to September 30, 2016 from the Optum EHR database were used to evaluate the effect of second-line agents for ITP. Identified patients had the following characteristics: 18 years or older, evidence of previous treatment with steroids or immune globulin products, and activity in the database for at least 6 months prior to and 12 months post initiation of a second-line agent. Treatment outcomes evaluated included platelet counts, bleeding related episodes (BREs), and thrombotic events (TEs) over the 12-month period following starting a second-line therapy.

Of the 2,526 adults that met the inclusion criteria, 110 (4.4%) received eltrombopag, 189 (7.5%) romiplostim, 1,488 (58.9%) rituximab, and 260 (10.3%) splenectomy, with the remaining 479 (18.9%) receiving a mix of other second-line agents. Compared to baseline, platelet counts increased in all treatment cohorts. The proportion of patients who experienced BREs ranged from 25.5% (eltrombopag) to 36.5% (romiplostim), while TEs were observed in all treatment cohorts ranging from 11.6% (eltrombopag) to 15.7% (splenectomy). An additional analysis demonstrated that patients with ITP who had a splenectomy as second-line treatment had the highest mean platelet counts during the first 12 months post treatment initiation, but were at greatest risk for TEs (15.7%) (e.g., stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis, and pulmonary embolism) compared to 11.6% (eltrombopag), 12.7% (romiplostim), and 13.9% (rituximab).

"These real-world data can help doctors as they weigh options for second-line therapy with their patients." Adam Cuker, MD, Assistant Professor of Medicine at the University of Pennsylvania. "They may also help explain the long-term trend toward deferring splenectomies until after other lines of treatment have been tried."

Immune thrombocytopenia is a rare and potentially serious blood disorder where there is an increased risk of bleeding due to a low number of platelets. As a result, patients with ITP experience bruising, bleeding and, in rare cases, serious hemorrhage that can be fatal.[1] The goal of treatment in chronic/persistent ITP is to maintain a safe platelet count that reduces the risk of bleeding.[1]

Promacta/Revolade (eltrombopag)
Eltrombopag, marketed as Promacta in the US and Revolade in countries outside the US, is approved in more than 90 countries worldwide for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenic purpura (ITP) who have had an inadequate response or are intolerant to other treatments. It is also approved for the treatment of patients with severe aplastic anemia (SAA) as first-line therapy in the US (patients 2 years and older) and Japan, and in many other countries for patients who are refractory to other treatments. In more than 40 countries, Promacta/Revolade is indicate for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy. Promacta/Revolade is approved in the US and in the European Union for the treatment of thrombocytopenia in pediatric patients 1 year and older with chronic immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. Promacta should only be used in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.

Important Safety Information
Promacta can cause serious side effects, including liver problems, abnormal liver function tests, high platelet counts and higher risk for blood clots, and new or worsened cataracts (a clouding of the lens in the eye).

Promacta is not for treatment of people with a precancerous condition called myelodysplastic syndromes (MDS). If you have MDS and receive Promacta, your MDS condition may worsen and become AML. If MDS worsens to become AML, you may die sooner from AML.

For patients who have chronic hepatitis C virus and take Promacta with interferon and ribavirin treatment, Promacta may increase the risk of liver problems. Patients should tell a healthcare provider right away if they have any of these signs and symptoms of liver problems including yellowing of the skin or the whites of the eyes (jaundice), unusual darkening of the urine, unusual tiredness, right upper stomach area pain, confusion, swelling of the stomach area (abdomen).

A healthcare provider will order blood tests to check the liver before starting Promacta and during Promacta treatment. In some cases, treatment with Promacta may need to be stopped due to changes in liver function tests.

The risk of getting a blood clot is increased if the platelet count is too high during treatment with Promacta. The risk of getting a blood clot may also be increased during treatment with Promacta if platelet counts are normal or low. Some forms of blood clots, such as clots that travel to the lungs or that cause heart attacks or strokes can cause severe problems or death. A healthcare provider will check blood platelet counts, and change the dose of Promacta or stop Promacta, if platelet counts get too high. Patients should tell a healthcare provider right away if they have signs and symptoms of a blood clot in the leg, such as swelling, pain, or tenderness in the leg.

People with chronic liver disease may be at risk for a type of blood clot in the stomach area. Patients should tell a healthcare provider right away if they have stomach area pain that may be a symptom of this type of blood clot.

New or worsened cataracts have happened in people taking Promacta. A healthcare provider will check the patient’s eyes before and during treatment with Promacta. Patients should tell a healthcare provider about any changes in eyesight while taking Promacta.

Patients should tell a healthcare provider about all the medicines they take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Promacta may affect the way certain medicines work. Certain medicines may keep Promacta from working correctly. Patients should take Promacta at least 4 hours before or 4 hours after taking products such as antacids used to treat stomach ulcers or heartburn and multivitamins or products that contain iron, calcium, aluminum, magnesium, selenium, and zinc, which may be found in mineral supplements. Patients should ask a healthcare provider if they are not sure if the medicine is one that is listed above.

Patients should avoid situations and medications that may increase the risk of bleeding while taking Promacta.

The most common side effects of Promacta when used to treat chronic ITP in adults are: nausea; diarrhea; upper respiratory tract infection (symptoms may include runny nose, stuffy nose, and sneezing); vomiting; muscle aches; urinary tract infection (symptoms may include frequent or urgent need to urinate, low fever in some people, pain or burning with urination); pain or swelling (inflammation) in the throat or mouth (oropharyngeal pain and pharyngitis); abnormal liver function tests; back pain; flu-like symptoms (influenza), including fever, headache, tiredness, cough, sore throat, and body aches; skin tingling, itching, or burning; and rash.

The most common side effects of Promacta in children 1 year and older when used to treat chronic ITP are: upper respiratory tract infections (symptoms may include runny nose, stuffy nose, and sneezing); pain or swelling (inflammation) in the nose and throat (nasopharyngitis); cough; diarrhea; pyrexia; runny, stuffy nose (rhinitis); stomach (abdominal) pain; pain or swelling (inflammation) in the throat or mouth; toothache; abnormal liver function tests; rash; runny nose (rhinorrhea).

The most common side effects when Promacta is used in combination with other medicines to treat chronic HCV are: low red blood cell count (anemia); fever; tiredness; headache; nausea; diarrhea; decreased appetite; flu-like symptoms (influenza), including fever, headache, tiredness, cough, sore throat, and body aches; feeling weak; trouble sleeping; cough; itching; chills; muscle aches; hair loss; and swelling in the ankles, feet, and legs.

The most common side effects of Promacta when used to treat severe aplastic anemia (SAA) are: nausea, feeling tired, cough, diarrhea, headache, pain in arms, legs, hands or feet, shortness of breath, fever, dizziness, pain in nose or throat, abdominal pain, bruising, muscle spasms, abnormal liver function tests, joint pain, and runny nose. Laboratory tests may show abnormal changes to the cells in bone marrow.

The most common side effects of Promacta when used to treat adults and pediatric patients 2 years and older with SAA in combination with standard immunosuppressive therapy are: abnormal liver function tests, rash and skin discoloration including darkening of skin patches
(hyperpigmentation).

On December 2, 2018 Bellicum Pharmaceuticals, Inc. (NASDAQ:BLCM), a leader in developing novel, controllable cellular immunotherapies for cancers and orphan inherited blood disorders, reported additional follow-up results from a subset of children with high-risk/relapsed acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) (Press release, Bellicum Pharmaceuticals, DEC 2, 2018, View Source [SID1234531780]). The data showed durable anti-leukemic effects in patients treated with rivo-celTM (rivogenlecleucel, formerly BPX-501) following αβT-cell and B-cell depleted allogeneic hematopoietic stem cell transplantation (HSCT). The data were reviewed in an oral presentation today at the 60th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2018) by Principal Investigator Franco Locatelli, M.D., Ph.D., Director of the Department of Hematology and Oncology and Cell/Gene Therapy at Ospedale Pediatrico Bambino Gesù in Rome, Italy.

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"Cancer recurrence is one of the primary factors affecting the success rate of allogeneic HSCT. Rivo-cel appears to lower the rate of cancer recurrence in children receiving αβT-cell and B-cell depleted allogeneic HSCT—suggesting that the diverse population of donor T cells in rivo-cel product may reduce or eliminate residual cancer cells," said Dr. Locatelli. "Moreover, while you might expect to see Graft versus Host Disease with this approach, the overall rates were low and rimiducid was effective for most patients who developed visceral GvHD or who were refractory to standard of care treatment for GvHD. These encouraging data support the potential of rivo-cel as an important treatment for children with blood cancers who need a stem cell transplant and lack a matched donor."

Study Design and Highlights

Investigators evaluated the safety and efficacy of rivo-cel administered after an αβT-cell and B-cell depleted haploidentical HSCT (haplo-HSCT) in pediatric patients with high-risk/relapsed acute leukemias in morphological complete remission (CR). The objective was to determine whether rivo-cel could extend relapse-free survival (RFS) and overall survival (OS) via graft versus leukemia (GvL) effect, while maintaining a low-risk of GvHD. 100 AML and ALL HSCT patients were evaluated for safety. 95 of 100 patients received rivo-cel treatment and therefore were eligible for efficacy evaluation. Patients had a median follow-up of 17 months. Results are summarized as follows:

Survival outcomes:

ALL
n = 52 AML
n = 43
Relapse-free survival
CR1
CR2

100.0%
73.2%

78.0%
88.8%
Overall Survival
CR1
CR2

100.0%
89.9%

86.7%
95.7%
GvHD outcomes:

21 of 96 evaluable patients developed Grade I-IV acute GvHD (21.9%); 3 patients developed Grade III-IV acute GvHD (3.1% [95% CI: 0 – 6.6%]) 9 cases of late-onset aGVHD occurred after 100 days (2 cases of Grade III) 7 of 89 evaluable patients developed chronic GvHD (10.9% [95% CI: 2.1-19.6%]), with moderate-severe cases in 5 of these patients
Rimiducid treatment outcomes:

Of the 37 patients who developed GvHD, rimiducid was administered to 11 patients Best overall response (within 7 days) was seen in 73% (8 patients); 5 responding patients had a complete response (CR) and 2 patients with a partial response (PR) went on to achieve a complete response within 30 days following rimiducid administration
Commented Rick Fair, President & CEO of Bellicum Pharmaceuticals, "We are extremely pleased by these data, which suggest rivo-cel may be a potent and durable leukemia treatment when added to stem cell transplant. We plan to continue to follow these patients to further evaluate durability. In addition, based on these exciting results, we are in final stages of initiating a global Phase 2/3 trial in patients 12 years and older with AML and myelodysplastic syndromes (MDS) by the end of the year."

A copy of the ASH (Free ASH Whitepaper) presentation will be made available in the Abstracts & Presentations section of the Company’s website.

Analyst and Investor Luncheon Event and Webcast
Bellicum will host a live and webcast analyst and investor luncheon event on December 3, 2018 at 12:00 p.m. – 1:30 p.m. PST in San Diego, CA. Featured speakers include Dr. Alice Bertaina, Associate Professor of Pediatrics, Stem Cell Transplantation, Lucile Packard Children’s Hospital at the Stanford School of Medicine, as well as Bellicum senior management. A webcast replay of the event will be available on the News & Events section of the Bellicum website, and available for at least two weeks following the event.

About Rivo-cel (BPX-501)
Rivo-celTM (rivogenlecleucel) is an allogeneic polyclonal T-cell product designed to accelerate immune recovery after HSCT and to reduce relapse of leukemia following a stem cell transplant. The cell treatment contains a diverse repertoire of T cells which may contribute to a robust graft vs. leukemia effect. Rivo-cel’s antiviral benefits may also reduce morbidity and mortality in patients susceptible to infection following a transplant. The product’s CaspaCIDe safety switch enables this approach by allowing physicians to reduce the number of alloreactive cells in the event of uncontrolled GvHD. Rivo-cel addresses a major unmet need in adult and pediatric leukemia, lymphoma and genetic blood disease patients following a haploidentical stem cell transplant.