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10-K – Annual report [Section 13 and 15(d), not S-K Item 405]

Insys Therapeutics has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission (Filing, 10-K, Insys Therapeutics, FEB 26, 2016, View Source [SID1234509324]).

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10-Q – Quarterly report [Sections 13 or 15(d)]

(Filing, 10-Q, Advaxis, FEB 26, 2016, View Source [SID:1234509250])

LAM-002A: What You Should Know about this Agent for B-cell Non-Hodgkin Lymphoma

On February 26, 2016 The Lymphoma Program at NewYork-Presbyterian and Weill Cornell Medicine reported new developments in lymphoma (Press release, Weill Cornell Medical College, FEB 26, 2016, View Source [SID:1234510763]).

What is LAM-002A?

LAM-002A is an oral selective kinase inhibitor currently undergoing Phase I trials for the treatment of relapsed or refractory B-cell non-Hodgkin lymphoma. These trials seek to evaluate the safety, tolerability, and pharmacokinetics of LAM-002A. Before investigation of LAM-002A in patients with lymphoma, it was studied and found to be safe in patients with psoriasis, rheumatoid arthritis (RA) and Crohn’s disease.

How does LAM-002 work?

Also known as apilimod dimesylate, LAM-002 is a potent and highly selective PIKfyve kinase inhibitor. It is the first compound in this class. Kinases are proteins that modify cell functions. Lymphomas can arise from overactive or high levels of kinases. LAM-002 disrupts the normal activity of this particular kinase, which can lead to death of cancer cells.

What are the side effects?

In previous studies of patients with psoriasis, RA and Crohn’s disease, LAM-002 was well tolerated, with most side effects assessed as mild in severity. The most frequent side effects included headaches, upper respiratory tract infection, and nausea. To date all available nonclinical and clinical data support the safety profile of LAM-002A in patients with non-Hodgkin lymphoma.

How can you access LAM-002A?

LAM-002A is available through a recently opened Phase I trial for men and women with previously-treated B-cell non-Hodgkin lymphoma in the Lymphoma Program at Weill Cornell Medicine.

Portola Pharmaceuticals Reports Fourth Quarter and Year-End 2015 Financial Results and Provides Corporate Update

On February 26, 2016 Portola Pharmaceuticals (Nasdaq:PTLA) reported a corporate update and its financial results for the fourth quarter and year ended December 31, 2015 (Press release, Portola Pharmaceuticals, FEB 26, 2016, View Source;p=RssLanding&cat=news&id=2143706 [SID:1234509238]).

"During the fourth quarter of 2015, we executed on several milestones that we expect will make 2016 a year of unprecedented progress. We plan to commercially launch andexanet alfa and report pivotal Phase 3 results from our APEX study that, if positive, will support the global approval of betrixaban," said Bill Lis, chief executive officer of Portola. "Both have the potential to benefit the patients and transform the field in the multibillion dollar thrombosis market. Additionally, our R&D pipeline continues to progress with our ongoing Phase 1/2 study with cerdulatinib, our oral, dual syk/JAK inhibitor in refractory/relapsed hematologic cancer patients."

Recent Achievements, Upcoming Events and Milestones

Betrixaban – an FDA-designated Fast Track oral Factor Xa inhibitor anticoagulant in development for the prevention of venous thromboembolism (VTE) in acute medically ill patients.

Plan to report topline results from the 7,514-patient pivotal Phase 3 APEX (Acute Medically Ill VTE Prevention with Extended Duration Betrixaban) Study in early April.

Plan to submit a New Drug Application to the FDA in the second half of 2016, subject to positive APEX data.

Andexanet alfa – an FDA-designated Breakthrough Therapy Factor Xa inhibitor antidote in development for reversal of anticoagulation in patients treated with a Factor Xa inhibitor and who are admitted to the hospital with uncontrolled bleeding or need urgent surgery.

The FDA accepted the Biologics License Application (BLA) for filing February 16, 2016. The BLA was granted a priority review under an Accelerated Approval pathway, and assigned a PDUFA date of August 17, 2016. We plan to launch andexanet alfa commercially in the U.S. in the second half of 2016, subject to FDA approval.

The full data set from the ANNEXA-R study with rivaroxaban was presented in a Late-Breaking Clinical Trial Session at the American Heart Association’s Scientific Sessions 2015 and simultaneously published in the New England Journal of Medicine.

Licensed development and commercial rights in Japan to Bristol-Myers Squibb Company and Pfizer Inc. Separately, entered into a clinical collaboration agreement with Bayer HealthCare to include its Factor Xa inhibitor rivaroxaban in the development program in Japan.

Continue to enroll patients in ANNEXA-4, a Phase 4 confirmatory study of patients receiving apixaban, rivaroxaban, edoxaban or enoxaparin who present to the hospital with an acute major bleed.

Plan to present data from the Phase 2 proof-of-concept andexanet study with betrixaban in healthy volunteers at a medical conference in 2016 The study was designed to evaluate safety and define the dose of andexanet required to reverse the anticoagulant effect of betrixaban.

Plan to complete FDA pre-approval inspection of the initial (Generation 1 2,500 liter scale at CMC Biologics). Generation 1 validation batch runs at the 6 x 2,000 liter scale are ongoing.

Completed two Generation 2 engineering batches manufactured by Lonza at the 10,000 liter scale, with target yields achieved. Expect commercial validation batches to begin in the second half of 2016.

Cerdulatinib – an oral, dual Syk/JAK kinase inhibitor in development to treat resistant or relapsed hematologic cancer patients.

Presented three abstracts at the 2015 ASH (Free ASH Whitepaper) Annual Meeting on cerdulatinib’s preclinical activity in chronic lymphocytic leukemia; clinical and pharmacodynamic results of a Phase 1/2 study with relapsed/refractory B cell malignancies; and pharmacokinetic modeling of cerdulatinib plasma concentrations in patients with relapsed/refractory B cell malignancies.

Continue to dose-escalate for clinical activity and tolerability in the ongoing Phase 1/2 study in patients with relapsed/refractory B-cell malignancies. Plan to initiate enrollment in expansion cohorts this year.

Corporate

Raised $162.7 million in net proceeds from an underwritten public offering of common stock in December 2015.

Fourth Quarter and Year-End Financial Results
Collaboration revenue earned under Portola’s collaborations with Bristol-Myers Squibb Company and Pfizer, Bayer Pharma and Janssen Pharmaceuticals, Daiichi Sankyo and Lee’s Pharmaceutical was $4.4 million for the fourth quarter of 2015 compared with $2.4 million for the fourth quarter of 2014. Collaboration revenue for the year ended December 31, 2015, was $12.1 million compared with $9.6 million for the year ended December 31, 2014.

Total operating expenses for the fourth quarter of 2015 were $70.7 million compared with $41.7 million for the same period in 2014. Total operating expenses for the fourth quarter of 2015 included $6.8 million in stock-based compensation expense compared with $2.5 million for the same period in 2014. Total operating expenses for the year ended December 31, 2015, were $239.2 million compared with $147.2 million for 2014. Total operating expenses for the full year ended December 31, 2015, included $22.9 million in stock-based compensation expense compared with $9.3 million for 2014. Research and development expenses were $200.4 million for the year ended December 31, 2015, compared with $123.6 million for 2014, as the Company continued to support its manufacturing scale-up of andexanet alfa in preparation for the BLA submission and commercial launch and work on its larger-scale Generation 2 manufacturing process at Lonza, its Phase 3 and Phase 4 ANNEXA studies of andexanet alfa, completing enrollment in the Phase 3 APEX Study of betrixaban, and its Phase 1/2a clinical study of cerdulatinib. Selling, general and administrative expenses for the fourth quarter of 2015 were $10.9 million compared with $7.0 million for the same period in 2014. Selling, general and administrative expenses for the year ended December 31, 2015, were $38.9 million compared with $23.6 million for 2014, as the Company increased headcount to support its growth and increased pre-commercial launch activities, including hiring key regional sales directors and national account managers and further developing medical affairs.

For the fourth quarter of 2015, Portola reported a net loss of $66.1 million, or $1.23 net loss per share, compared with a net loss of $39.3 million, or $0.82 net loss per share, for the same period in 2014. Net loss for the year ended December 31, 2015, was $226.5 million, or $4.36 net loss per share, compared with a net loss of $137.1 million, or $3.19 net loss per share, for the same period in 2014.

Cash, cash equivalents and investments at December 31, 2015, totaled $460.2 million compared with cash, cash equivalents and investments of $392.3 million as of December 31, 2014.

FDA approves new indication for Novartis drug Afinitor® for progressive, nonfunctional GI and lung neuroendocrine tumors (NET)

On February 26, 2016 Novartis reported that the United States Food and Drug Administration (FDA) approved Afinitor (everolimus) tablets for the treatment of adult patients with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic (Press release, Novartis, FEB 26, 2016, View Source [SID:1234509242]).

Afinitor received a priority review designation providing a shortened review period for drugs that treat serious conditions and offer a significant improvement in safety or effectiveness.

"Afinitor is the first treatment approved for progressive, nonfunctional NET of lung origin, and one of very few options available for progressive, nonfunctional GI NET, representing a shift in the treatment paradigm for these cancers," said Bruno Strigini, President, Novartis Oncology. "We are proud of our Afinitor development program, which has translated to meaningful benefits for patients with several different cancers and rare diseases."

Neuroendocrine tumors are a rare type of cancer that originate in neuroendocrine cells throughout the body, and are most often found in the GI tract, lungs or pancreas[1],[4]. NET can be defined as functional or nonfunctional. Functional NET are characterized by symptoms caused by the oversecretion of hormones and other substances. Nonfunctional NET may be characterized by symptoms caused by tumor growth, such as intestinal obstruction, pain and bleeding for GI NET, and asthma, chronic obstructive pulmonary disease and pneumonia for lung NET[5],[6],[7],[8]. More than 70% of patients with NET have nonfunctional tumors[9]. At the time of diagnosis, 5%-44% (depending on site of tumor origin) of patients with NET in the GI tract and 28% of patients with lung NET have advanced disease, meaning the cancer has spread to other areas of the body, making it difficult to treat[1],[4]. Progression, or the continued growth or spread of the tumor, is typically associated with poor outcomes[10].

The approval of Afinitor was based on efficacy and safety data from a pivotal study (RADIANT-4) showing Afinitor reduced the risk of progression in patients with progressive, well-differentiated, nonfunctional NET of GI or lung origin by 52% (hazard ratio [HR] = 0.48; 95% confidence interval [CI], 0.35-0.67; p<0.001) vs placebo. Additionally, the data showed Afinitor increased median progression-free survival (PFS) by 7.1 months: median PFS by central review was 11.0 months (95% CI, 9.2-13.3) in the Afinitor arm and 3.9 months (95% CI, 3.6-7.4) in the placebo arm[3].

In the pivotal trial, the most common treatment-related grade 3/4 adverse events (AEs) (>=5%) for Afinitor and placebo, respectively, were infections (11.0% vs 2.0%), diarrhea (9.0% vs 2.0%), stomatitis (9.0% vs 0.0%), fatigue (5.0% vs 1.0%) and hyperglycemia (5.0% vs 0.0%)[3].

Additional worldwide regulatory filings for this indication are underway, with a decision in the EU anticipated in 2016.

RADIANT-4 Study: Part of the largest clinical trial program in advanced NET
RADIANT-4 (RAD001 In Advanced Neuroendocrine Tumors) is a Phase III prospective, double-blind, randomized, parallel group, placebo-controlled, multicenter study. It examined the efficacy and safety of Afinitor plus best supportive care (BSC) vs placebo plus BSC in 302 patients with unresectable, progressive, well-differentiated, nonfunctional, locally advanced or metastatic NET of GI (excluding pancreatic) or lung origin. The major efficacy outcome measure of RADIANT-4 was PFS based on independent radiological assessment evaluated by Response Evaluation Criteria in Solid Tumors. Additional efficacy outcome measures were overall survival and best overall response rate (defined as complete response plus partial response)[3].

Patients were randomized 2:1 to receive daily Afinitor 10 mg or daily placebo orally. All patients received BSC during treatment, which excluded somatostatin analogues (SSAs). Patients had low or intermediate grade histology, no history or active symptoms of carcinoid syndrome, had documented disease progression within the previous 6 months and were required to have ceased treatment with SSAs for 4 weeks before study entry[3],[11].

The safety profile of Afinitor was consistent with what has been observed in previous studies of this drug. The most common treatment-related, all-grade AEs (incidence >=30%) were stomatitis (63%), infections (58%), diarrhea (41%), peripheral edema (39%), fatigue (37%) and rash (30%). Afinitor was discontinued for adverse reactions in 29% of patients and dose reduction or delay was required in 70% of Afinitor-treated patients[3].

About Afinitor (everolimus) tablets
Afinitor (everolimus) tablets is now approved by the United States (US) Food and Drug Administration (FDA) for the treatment of adult patients with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NET) of gastrointestinal (GI) or lung origin that are unresectable, locally advanced or metastatic. Additionally, Afinitor is approved in 99 countries, including the US and throughout the European Union, for locally advanced, metastatic or unresectable progressive NET of pancreatic origin. It is also approved in >120 countries including the US and European Union for advanced renal cell carcinoma following progression on or after vascular endothelial growth factor (VEGF)-targeted therapy (in the US, specifically following sunitinib and sorafenib).

Afinitor is also approved in 102 countries including the US and European Union for advanced HR+/HER2- breast cancer in combination with exemestane, after prior endocrine therapy.

Everolimus is also available from Novartis for use in certain non-oncology patient populations under the brand names Afinitor or Votubia, Certican and Zortress and is exclusively licensed to Abbott and sublicensed to Boston Scientific for use in drug-eluting stents.

Indications vary by country and not all indications are available in every country. The safety and efficacy profile of everolimus has not yet been established outside the approved indications. Because of the uncertainty of clinical trials, there is no guarantee that everolimus will become commercially available for additional indications anywhere else in the world.

Important Safety Information about Afinitor (everolimus) tablets
Afinitor/Votubia can cause serious side effects including lung or breathing problems, infections (including sepsis), and kidney failure, which can lead to death. Patients taking concomitant angiotensin-converting enzyme (ACE) inhibitors may be at an increased risk for angioedema. Mouth ulcers and mouth sores are common side effects. Afinitor/Votubia can affect blood cell counts, kidney and liver function, and blood sugar, cholesterol, and triglyceride levels. Afinitor/Votubia may cause fetal harm in pregnant women. Highly effective contraception is recommended for women of child-bearing potential while receiving Afinitor/Votubia and for up to eight weeks after ending treatment. Women taking Afinitor/Votubia should not breast feed. Fertility in women and men may be affected by treatment with Afinitor/Votubia.

The most common adverse drug reactions (incidence >=10 percent) are mouth ulcers, skin rash, feeling tired or weak, diarrhea, infections (including upper respiratory tract infection, sore throat and runny nose, sinusitis, middle ear infection and pneumonia), absence of menstrual periods, high levels of cholesterol, nausea, decreased appetite, low level of red blood cells, acne, abnormal taste, irregular menstrual periods, inflammation of lung tissue, swelling of extremities or other parts of the body, high level of blood sugar, itching, weight loss, nose bleeds, cough and headache. The most common grade 3-4 adverse drug reactions (incidence >=2 percent) are mouth ulcers, infections (including pneumonia), low level of red blood cells, absence of menstrual periods, high level of blood sugar, feeling tired or weak, diarrhea, low white blood cells, inflammation of lung tissue and spontaneous bleeding or bruising. Cases of hepatitis B reactivation, blood clots in the lung or legs, and pneumocystis jirovecii pneumonia (PJP) have been reported. Abnormalities were observed in hematology and clinical chemistry laboratory tests.