U.S. and European Regulators Accept Venetoclax for Chronic Lymphocytic Leukemia

AbbVie announced that the U.S. Food and Drug Administration (FDA) accepted AbbVie's New Drug Application (NDA) granting priority review for venetoclax for the treatment of chronic lymphocytic leukemia (CLL) in adults who have received at least one prior therapy, including patients with 17p deletion. With priority review, the FDA's goals include a faster timeline for review of six months, compared to 10 months for the standard review period. Additionally, AbbVie announced the European Medicines Agency (EMA) has validated its Marketing Authorization Application (MAA) for venetoclax for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion or TP53 mutation.

 

Venetoclax is an inhibitor of the B-cell lymphoma-2 (BCL-2) protein being developed in partnership with Genentech and Roche to treat CLL. Venetoclax is believed to lead some cells, including some cells with CLL, to undergo apoptosis, or cell death.

The FDA granted venetoclax Breakthrough Therapy Designation (BTD) in April 2015 for the treatment of CLL in previously treated patients with the 17p deletion genetic mutation, underscoring the potential for venetoclax to provide substantial improvement over current therapies in this difficult to treat patient population.

IBRUTINIB COMBINATION DATA SHOW PROMISE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

AbbVie announced preliminary data from the ongoing Phase 1/2b PCYC-1119 trial suggesting that the combination of ibrutinib (IMBRUVICA^®) plus carfilzomib with or without dexamethasone was well tolerated in relapsed or refractory patients with multiple myeloma (MM), with an initial objective response rate (ORR) of 62%. These data will be presented today in an oral presentation at the 57th Annual American Society of Hematology (ASH) Meeting and Exposition in Orlando, FL at 5:30 p.m. ET. IMBRUVICA is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie Company, and Janssen Biotech, Inc.

MM is a blood cancer that most commonly arises from B cells, a type of white blood cell (lymphocyte) that originates in the bone marrow. This year, approximately 26,850 people will be diagnosed with the disease and about 11,240 will die. 

IMBRUVICA is currently approved for the treatment of patients with chronic lymphocytic leukemia (CLL) who have received at least one prior therapy, CLL patients who have del 17p and patients with Waldenström's macroglobulinemia.  IMBRUVICA is also approved for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Accelerated approval was granted for the MCL indication based on overall response rate. Continued approval for this indication may be contingent upon verification of clinical benefit in confirmatory trials.

AbbVie released PHASE 1 Clinical Data of VENETOCLAX

AbbVie announced the online publication of new data in the New England Journal of Medicine (NEJM) showing some patients with relapsed/refractory chronic lymphocytic leukemia (CLL) treated with venetoclax experienced a response, including complete responses. The article reports data from Arm A of the study, in which all patients had relapsed CLL and more than one-third were refractory to their last treatment. Venetoclax is an investigational, first-in-class, B-cell lymphoma-2 (BCL-2) inhibitor being developed and commercialized by AbbVie and Genentech and Roche.

In arm A of the M12-175 study, venetoclax had an overall response rate of 79 percent (n=92/116) and complete response in 20 percent of patients. Serious adverse events (AEs) occurring in ≥ 2 percent of patients were febrile neutropenia, pneumonia, immune thrombocytopenia, tumor lysis syndrome, diarrhea, fluid overload, hyperglycemia, prostate cancer, pyrexia, upper respiratory tract infection, and viral upper respiratory tract infection. Grade 3 or 4 AEs occurring in ≥ 2 percentof patients were diarrhea, nausea, neutropenia, fatigue, anemia, thrombocytopenia, vomiting and hyperglycemia.

CLL is a typically slow-progressing cancer of the bone marrow and blood in which the bone marrow makes too many lymphocytes, a type of white blood cell.  Approximately 3-10 percent of CLL patients have 17p deletion at diagnosis. The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent.

Venetoclax is an investigational oral BCL-2 inhibitor being evaluated for the treatment of patients with various cancer types. The BCL-2 protein prevents apoptosis of some cells, including lymphocytes, and can be over expressed in some cancer types. Venetoclax is designed to selectively inhibit the function of the BCL-2 protein. Venetoclax is being developed in collaboration with Genentech and Roche. Together, the companies are committed to BCL-2 research with venetoclax, which is currently being evaluated in Phase 3 clinical trials for the treatment of relapsed/refractory CLL, along with studies in several other cancers. Venetoclax is an investigational compound and its safety and efficacy have not been evaluated by the FDA or any other health authority.

FDA ACCEPT NDA For VIEKIRA PAK

AbbVie  a global biopharmaceutical company, announced its New Drug Application (NDA) has been accepted by the U.S. Food and Drug Administration (FDA) for a once-daily, fixed-dose formulation of the components of VIEKIRA PAK (ombitasvir, paritaprevir, and ritonavir tablets; dasabuvir tablets). VIEKIRA PAK is an all-oral, interferon-free treatment approved with or without ribavirin (RBV) in the United States for patients with genotype 1 (GT1) chronic hepatitis C virus (HCV) infection, including those with compensated cirrhosis. VIEKIRA PAK is not for people with decompensated cirrhosis.

The proposed dosing for the fixed-dose formulation (dasabuvir, ombitasvir, paritaprevir, ritonavir tablets) is three oral tablets once daily with a meal, with or without twice-daily RBV, potentially offering another important treatment option for people living with GT1 HCV. The NDA filing is supported by data from two bioavailability studies. Currently, VIEKIRA PAK is taken twice daily as three tablets in the morning and one tablet in the evening, taken with a meal.

The Centers for Disease Control and Prevention (CDC) estimates that in the United States, approximately 2.7 million people are chronically infected with HCV. Genotype 1 is the most prevalent form of HCV in the U.S., accounting for approximately 74 percent of all cases. Hepatitis C is inflammation of the liver caused by an infection with HCV. It is transmitted when an infected person's blood enters the bloodstream of an uninfected person. There are six major HCV genotypes (GT1-6). Presently, there is no vaccine for HCV infection.

AbbVie Announces Phase 2 Studies ABT-493

AbbVie announced data from the SURVEYOR studies of its investigational HCV regimen, ABT-493, an NS3/4A protease inhibitor, and ABT-530, an NS5A inhibitor, that show high rates of sustained virologic response at 12 weeks post-treatment (SVR₁₂) in non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. After 12 weeks of treatment, SVR₁₂ rates achieved were 97-100 percent in genotype 1 (GT1), 96-100 percent in genotype 2 (GT2) and 83-94 percent in genotype 3 (GT3) patients.These data are being presented at The Liver Meeting^® 2015, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in San Francisco. 

Separately, in a late-breaking presentation of the SURVEYOR-I study, data show non-cirrhotic GT1 chronic HCV patients who received a shorter duration of treatment for 8 weeks with ABT-493 and ABT-530 achieved a SVR₁₂ rate of 97 percent.

^{SURVEYOR-I and SURVEYOR-II are ongoing Phase 2 clinical studies that evaluate the safety and efficacy of ABT-493 and ABT-530, with or without ribavirin (RBV), for 8 to 12 weeks. These data presented at AASLD include non-cirrhotic patients with GT1, GT2 and GT3 chronic HCV infection. Data in additional patient populations (genotypes 4-6) will be presented at future meetings.} 

VIEKIRAX Receives Approval in Japan

AbbVie a global biopharmaceutical company, announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) approved VIEKIRAX^® (ombitasvir/paritaprevir/ritonavir), as a new interferon and ribavirin-free treatment option for adult patients with chronic genotype 1 (GT1) hepatitis C virus (HCV) infection, including those with compensated liver cirrhosis. VIEKIRAX consists of a 12-week, two direct-acting antiviral, fixed-dose combination of paritaprevir/ritonavir with ombitasvir, dosed once daily. 

Japan has one of the highest rates of hepatitis C infection in the industrialized world, with approximately 1.5 to 2 million people living with HCV. Genotype 1 is the most common HCV genotype in Japan with 60 to 70 percent of patients infected and, of those, about 95 percent are infected with the genotype 1b (GT1b) sub-type.

The approval is supported by the Phase 3 GIFT-I study. An overall 95 percent (n=140/148) of treatment-naïve and 94 percent (n=102/109) of treatment-experienced GT1b HCV infected patients achieved SVR₁₂ with VIEKIRAX. The primary endpoint was achieved, demonstrating 95 percent (n=106/112) SVR₁₂ in a sub-group of treatment-naïve, non-cirrhotic, adult GT1b HCV infected Japanese patients who were eligible for therapy with interferon (IFN) and had a high viral load. A secondary endpoint in GT1b HCV patients with compensated cirrhosis achieved 91 percent (n=38/42) SVR₁₂.

Across all treatment arms three patients (n=3/363) experienced on-treatment virologic failure, eight patients (n=8/354) experienced post-treatment relapse and three patients discontinued treatment due to adverse events. The most commonly reported adverse events (>5 percent in any arm) were nasopharyngitis, headache, peripheral edema, nausea, pyrexia and decreased platelet count. In April 2015, AbbVie was granted priority review by the MHLW for VIEKIRAX, on the basis of clinical usefulness of the treatment and recognizing the severity and unmet need of the disease in Japan.

Reports suggest that HIGH SUSTAINED VIRAL RESPONSE RATES WITH VIEKIRAX

New real world interim data from the independent AMBER study were presented for AbbVie's VIEKIRAX (ombitasvir/paritaprevir/ritonavir tablets) + EXVIERA (dasabuvir tablets) with or without ribavirin (RBV) in genotype 1 (GT1) chronic hepatitis C virus (HCV) infected patients. The primary endpoint of the study is the percentage of patients achieving sustained virologic response at 12 weeks post-treatment (SVR₁₂). This study of Polish patients who reached post-treatment at week 12 (n=40 of 186 enrolled to date), demonstrated 98 percent (n=39/40) SVR₁₂.¹ These results further help to support the GT1 data shown in AbbVie's Phase 3 clinical trial development program. Interim data from the AMBER study were presented at the Viral Hepatitis Congress in Frankfurt, Germany.

Interim safety analysis of the enrolled 186 patients reported that adverse events experienced were mostly mild, most commonly (>10%) fatigue, nausea and headache. Serious adverse events were infrequent (4%, n=186), which included hepatic decompensation, anemia, kidney insufficiency hepatotoxicity.

The AMBER study is a multicenter, independent investigator-initiated, open-label study that was conducted in Poland. Patients infected with GT1 (n=186) or genotype 4 (n=10) chronic HCV received VIEKIRAX + EXVIERA (co-formulated ombitasvir/paritaprevir/ritonavir (25/150/100 mg QD) ± dasabuvir (250 mg BID) ± RBV) for 12 or 24 weeks according to current product prescribing information. Patient visits were scheduled on day zero, end of treatment and at follow-up week 12. The study population included treatment naïve as well as pegylated-interferon/ribavirin treatment-experienced patients with varying levels of liver fibrosis. Of the 186 enrolled GT1 patients, at baseline, 21 percent of patients were treatment-naïve, 70 percent had been previously treated and 75 percent had levels of liver fibrosis of F3 or F4.