FDA Approves Odefsey (emtricitabine, rilpivirine and tenofovir alafenamide) for the Treatment of HIV-1 Infection

Gilead Sciences, Inc announced that the U.S. Food and Drug Administration (FDA) has approved Odefsey (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir alafenamide 25 mg or R/F/TAF) for the treatment of HIV-1 infection in certain patients. Emtricitabine and tenofovir alafenamide are from Gilead Sciences and rilpivirine is from Janssen Sciences Ireland UC, one of the Janssen Pharmaceutical Companies of Johnson & Johnson (Janssen). Odefsey is Gilead’s second TAF-based regimen to receive FDA approval and represents the smallest pill of any single tablet regimen for the treatment of HIV.

Emtricitabine  Rilpivirine  Tenofovir alafenamide

Odefsey is indicated as a complete regimen for the treatment of HIV-1 infection in patients 12 years of age and older who have no antiretroviral treatment history and HIV-1 RNA levels less than or equal to 100,000 copies per mL. Odefsey is also indicated as replacement for a stable antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) for at least six months with no history of treatment failure and no known substitutions associated with resistance to the individual components of Odefsey. No dosage adjustment of Odefsey is required in patients with estimated creatinine clearance greater than or equal to 30 mL per minute.

Odefsey has a boxed warning in its product label regarding the risks of lactic acidosis/severe hepatomegaly with steatosis, and post treatment acute exacerbation of hepatitis B.

TAF is a novel targeted prodrug of tenofovir that has demonstrated high antiviral efficacy similar to and at a dose less than one-tenth that of Gilead’s Viread (tenofovir disoproxil fumarate, TDF). TAF has also demonstrated improvement in surrogate laboratory markers of renal and bone safety as compared to TDF in clinical trials in combination with other antiretroviral agents. Data show that because TAF enters cells, including HIV-infected cells, more efficiently than TDF, it can be given at a much lower dose and there is 90 percent less tenofovir in the bloodstream.

FDA Approves Odefsey (emtricitabine, rilpivirine and tenofovir alafenamide) for the Treatment of HIV-1 Infection

FDA Approves Imbruvica (ibrutinib) for the First-Line Treatment of Chronic Lymphocytic Leukemia

In continuation of my update on Ibrutinib 

AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced the U.S. Food and Drug Administration (FDA) approved Imbruvica (ibrutinib) as a first-line treatment for patients with chronic lymphocytic leukemia (CLL).1 The approval is based on data from the randomized, multi-center, open-label Phase 3 RESONATE™-2 (PCYC-1115) trial, which evaluated the use of Imbruvica versus chlorambucil in 269 treatment-naïve patients with CLL or small lymphocytic lymphoma (SLL) aged 65 years or older. The RESONATE-2 data were previously presented at the American Society of Hematology (ASH) Annual Meeting in December 2015 and also simultaneously published in The New England Journal of Medicine. Imbruvica is jointly developed and commercialized by Pharmacyclics LLC, an AbbVie company and Janssen Biotech, Inc.

"This approval represents a significant leap forward for patients diagnosed with CLL who may want to consider an alternative first-line treatment to traditional chemotherapy," said Michael Severino, M.D., executive vice president, research and development and chief scientific officer, AbbVie. "AbbVie is committed to making significant improvements in the lives of patients with hematologic malignancies and will continue to explore ways to improve treatment options for patients."

The prevalence of CLL is approximately 115,000 patients in the U.S.2 with approximately 15,000 newly diagnosed patients every year.3 CLL is a disease of elderly patients, with an average diagnosis age of 71.3

The National Comprehensive Cancer Network (NCCN) recently published an update to its clinical practice guidelines for non-Hodgkin's lymphomas, granting Imbruvica a category 1 recommendation for certain CLL patients, the highest recommendation assigned by the organization. Specifically, NCCN recommends Imbruvica as a first-line treatment option for frail CLL patients with significant comorbidities, as well as for CLL patients with or without del 17p or the genetic mutation TP53 who are 70 years or older, or younger patients with significant comorbidities. The NCCN guidelines inform prescribing and reimbursement practices in many institutions in the U.S. and internationally.

"The progression-free survival data seen in these previously untreated CLL patients are strong and encouraging," said Dr. Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and the RESONATE-2 lead study investigator.* "This is especially important for first-line CLL patients, when considering the safety profile. This treatment represents another option for these patients."

FDA Approves Imbruvica (ibrutinib) for the First-Line Treatment of Chronic Lymphocytic Leukemia

FDA Expands Use of Xalkori (crizotinib) to Treat ROS-1 Positive Non-Small Cell Lung Cancer

In continuation of my update on Xalkori (crizotinib) 

The U.S. Food and Drug Administration today approved Xalkori (crizotinib) to treat people with advanced (metastatic) non-small cell lung cancer (NSCLC) whose tumors have an ROS-1 gene alteration. Xalkori is the first and only FDA approved treatment for patients with ROS-1 positive NSCLC.

Lung cancer is the leading cause of cancer-related deaths in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. ROS-1 gene alterations, thought to lead to abnormal cells, have been identified in various cancers, including NSCLC. ROS-1 gene alterations are present in approximately 1 percent of patients with NSCLC. The overall patient and disease characteristics of NSCLC with ROS-1 gene alterations appear similar to NSCLC with anaplastic lymphoma kinase (ALK) gene alterations, for which crizotinib use was previously approved. Xalkori was approved to treat certain patients with late-stage NSCLC that expresses an abnormal ALK gene in 2011.

“Lung cancer is difficult to treat, in part, because patients have different mutations, some of which are rare,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “The expanded use of Xalkori will provide a valuable treatment option for patients with the rare and difficult to treat ROS-1 gene mutation by giving health care practitioners a more personalized way of targeting ROS-1 positive NSCLC.”

Xalkori is an oral medication that blocks the activity of the ROS-1 protein in tumors that have ROS-1 gene alterations. This effect on ROS-1 may prevent NSCLC from growing and spreading.

The safety and efficacy of Xalkori for the treatment of patients with ROS-1 positive tumors were evaluated in a multi-center, single-arm study of 50 patients with ROS-1 positive metastatic NSCLC. Patients received Xalkori twice daily to measure the drug’s effect on their lung cancer tumors. The studies were designed to measure overall response rate, the percentage of patients who experienced complete or partial shrinkage of their tumors. Results showed 66 percent of participants experienced a complete or partial shrinkage of their NSCLC tumors, an effect that lasted a median of 18.3 months.

FDA Expands Use of Xalkori (crizotinib) to Treat ROS-1 Positive Non-Small Cell Lung Cancer

RUVICA (ibrutinib) capsules approved for treatment-naïve CLL patients

In continuation of my update on ibrutinib

The U.S. Food and Drug Administration (FDA) has approved IMBRUVICA® (ibrutinib) capsules for treatment-naïve patients with chronic lymphocytic leukemia (CLL). The approval is based on data from the Phase 3 RESONATE-2 (PCYC-1115) study, the first head-to-head clinical trial comparing IMBRUVICA to a chemotherapy agent. Results showed IMBRUVICA significantly extended progression-free survival (PFS; the primary endpoint) and increased overall response rate (ORR; a key secondary endpoint) compared to chlorambucil in previously untreated patients with CLL age 65 or older. IMBRUVICA is now approved for use in all lines of CLL therapy, considerably expanding the number of patients who may benefit from this treatment. This broadens the indication beyond the initial CLL approval in February 2014 for the treatment of patients with CLL who have received at least one prior therapy and in July 2014 for CLL patients with del 17p, a genetic mutation typically associated with poor treatment outcomes. IMBRUVICA is jointly developed and commercialized by Janssen Biotech, Inc. and Pharmacyclics LLC, an AbbVie company.

On a related front, the National Comprehensive Cancer Network® (NCCN) published an update on February 17 to its Clinical Practice Guidelines for non-Hodgkin's lymphomas recommending IMBRUVICA for certain first-line CLL patients.

"People living with CLL who have not been previously treated now have an option that significantly improved progression-free survival when compared to the oral chemotherapy used in the RESONATE-2 trial," said Jan Burger, M.D., Ph.D., Associate Professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX and RESONATE-2 study lead investigator. "The results seen in the RESONATE-2 clinical trial are truly compelling and make this medicine an attractive first-line treatment option for clinicians in the hematology space."

RUVICA (ibrutinib) capsules approved for treatment-naïve CLL patients:

The U.S. Food and Drug Administration has approved IMBRUVICA (ibrutinib) capsules for treatment-naïve patients with chronic lymphocytic leukemia (CLL).

Novartis announces FDA approval of Afinitor for progressive, nonfunctional neuroendocrine tumors of GI

 

In continuation of my update  on Everolimus 

Novartis today announced 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. 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. 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. More than 70% of patients with NET have nonfunctional tumors. 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. Progression, or the continued growth or spread of the tumor, is typically associated with poor outcomes.

Novartis announces FDA approval of Afinitor for progressive, nonfunctional neuroendocrine tumors of GI

New drug shows promise against Huntington's disease

A drug that would be the first to target the cause of Huntington's disease (HD) is effective and safe when tested in mice and monkeys, according to data released today that will be presented at the American Academy of Neurology's 68th Annual Meeting in Vancouver, Canada, April 15 to 21, 2016. A study to test the drug in humans has begun.

Huntington's disease is a rare, hereditary disease that causes uncontrolled movements, loss of intellectual abilities, emotional problems and eventually death. The disease is passed from parent to child through a mutation in the huntingtin gene. The mutation results in the production of a disease-causing huntingtin protein. Each child has a 50/50 chance of inheriting the gene mutation. Everyone who inherits the mutated gene will eventually develop the disease.

The new drug, called IONIS-HTTRx, is an antisense drug that acts as a "gene silencer" to inhibit the production of huntingtin protein in people with Huntington's disease.

"It is very exciting to have the possibility of a treatment that could alter the course of this devastating disease," said clinical study principal investigator Blair R. Leavitt, MD, of the University of British Columbia in Vancouver. "Right now we only have treatments that work on the symptoms of the disease." Leavitt notes the drug is still years away from being used in human clinical practice.

Earlier studies in mouse models of Huntington's disease showed that treatment with antisense drugs delays disease progression and results in sustained reversal of the disease phenotype. In YAC128 mice, a transgenic model of HD, motor deficits improved within one month of initiating antisense treatment and were restored to normal at two months after treatment termination. Motor skills of antisense-treated BACHD mice, another transgenic model of HD, improved eight weeks after initiation of treatment and persisted for at least nine months after treatment termination. In monkeys, dose-dependent reductions in HTT mRNA and Htt protein throughout the central nervous system were observed after intrathecal administration of an antisense drug. Reduction of cortical huntingtin levels by 50 percent was readily achieved in monkeys and correlated with 15 to 20 percent reduction in the caudate. In further tests in rodents and monkeys, IONIS-HTTRx was found to be well-tolerated without any dose-limiting side effects.

New drug shows promise against Huntington's disease

PCSK9-inhibitor drugs: A game-changer for individuals with extremely high cholesterol levels

A 59-year-old heart patient with dangerously high levels of cholesterol that could not be adequately reduced by statin drugs now has near-normal cholesterol levels, thanks to a new class of drugs that grew out of work done by UT Southwestern Medical Center researchers.

Two of these drugs, in a category known as PCSK9 inhibitors, were approved by the Food and Drug Administration last summer for use by some individuals with extremely high cholesterol levels.

"If you take the core patients who are at highest risk, it makes you appreciate how important this drug class is," said Dr. Amit Khera, Director of the Preventive Cardiology Program and Associate Professor of Internal Medicine at UT Southwestern.

Frank Brown of Dallas, grandfather of six and the owner of Frank's Wrecker Service in Dallas, has familial hypercholesterolemia, an inherited condition that causes high levels of cholesterol, especially low-density lipoprotein (LDL) cholesterol or "bad cholesterol." High levels of LDL cholesterol are strongly associated with heart disease.

Mr. Brown, with a history of two heart attacks, had been aggressively treated with multiple drugs to reduce his cholesterol levels, but they remained stubbornly high.

"When I first met Mr. Brown, he had a strong family history of heart disease, he had a cholesterol level that was ridiculously high with an LDL of 384, and he was having chest pains," said Dr. Amit Khera, who is Mr. Brown's cardiologist.

Dr. Khera, who holds the Dallas Heart Ball Chair in Hypertension and Heart Disease at UT Southwestern, was treating Mr. Brown with three cholesterol-lowering medications: a statin, which is a class of drugs that works by blocking a substance the body needs to make cholesterol; ezetimibe, a drug that blocks absorption of cholesterol in the intestine; and colesevelam, which sequesters bile acids. Even with this trio of medicines, Mr. Brown's LDL cholesterol level hovered around 200.

PCSK9-inhibitor drugs: A game-changer for individuals with extremely high cholesterol levels

Steroid May Be Safe, Effective Gout Treatment, Study Finds

A steroid pill may be as good as a nonsteroidal anti-inflammatory drug (NSAID) for treating painful gout, new research suggests.

Researchers who compared the steroid prednisolone with the arthritis medication indomethacin found both drugs offered a similar degree of pain reduction. And while indomethacin (Indocin) appeared to cause more minor side effects, neither treatment prompted serious complications, the researchers said.

        (Prednisole) (Indomethacin)

Smaller investigations have pointed in the same direction, said study lead author Dr. Timothy Rainer, a professor of emergency medicine at Cardiff University in Wales. But because the new findings are the product of a "larger and better-designed" effort, Rainer said steroid pills may gain standing among gout experts who usually stick with NSAIDs as their first-line treatment.

The bottom line is that there are choices, said Dr. Philip Mease, a rheumatologist with the Swedish Medical Center in Seattle.

"That is the key message - that there are options," said Mease, who wasn't involved in the study. "Sometimes ER docs don't think about giving a tapering dose of prednisone, but it can be very effective at helping with gout, which can be damn painful."

Steroid May Be Safe, Effective Gout Treatment, Study Finds 

New molecule has potential to prolong life of cystic fibrosis patients

New molecule has potential to prolong life of cystic fibrosis patients: Scientists at Queen's University Belfast have discovered a new molecule which has the potential to prolong the life of individuals with cystic fibrosis (CF).

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

In continuation of my updates on palbociclib

Pfizer Inc. (NYSE:PFE) announced that the U.S. Food and Drug Administration (FDA) has approved a new indication expanding the use of Ibrance (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer therapy. Now Ibrance also is approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.1 Pfizer’s supplemental New Drug Application (sNDA) for Ibrance was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs based on results from the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy in the adjuvant or metastatic setting.

Ibrance first was approved in February 2015 and also is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.

Ibrance is the first and only cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor approved by the FDA.

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

FDA Approves Briviact (brivaracetam) to Treat Partial Onset Seizures

The U.S. Food and Drug Administration yesterday approved Briviact (brivaracetam) as an add-on treatment to other medications to treat partial onset seizures in patients age 16 years and older with epilepsy.

Epilepsy is a brain disorder that causes people to have recurring seizures. A seizure is an episode, usually of relatively short duration, of abnormal brain activity. Seizures can cause a variety of symptoms, including uncontrolled movements or spasms, abnormal thinking and behavior, and abnormal sensations. Muscle spasms can be violent, and loss of consciousness can occur. Seizures occur when clusters of nerve cells (neurons) in the brain undergo uncontrolled activation. A partial onset seizure begins in a limited area of the brain.

“Patients can have different responses to the various seizure medicines that are available,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. “With the approval of Briviact, I am pleased that patients with epilepsy have a new treatment option.”

FDA Approves Briviact (brivaracetam) to Treat Partial Onset Seizures

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

In continuation of my updates on palbociclib

Pfizer Inc. (NYSE:PFE) announced that the U.S. Food and Drug Administration (FDA) has approved a new indication expanding the use of Ibrance (palbociclib) 125mg capsules, Pfizer’s metastatic breast cancer therapy. Now Ibrance also is approved for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced or metastatic breast cancer in combination with fulvestrant in women with disease progression following endocrine therapy.1 Pfizer’s supplemental New Drug Application (sNDA) for Ibrance was reviewed and approved under the FDA’s Breakthrough Therapy designation and Priority Review programs based on results from the Phase 3 PALOMA-3 trial in pre-, peri- and post-menopausal women with HR+, HER2- metastatic breast cancer whose disease progressed on or after prior endocrine therapy in the adjuvant or metastatic setting.

Ibrance first was approved in February 2015 and also is indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with letrozole as initial endocrine-based therapy in postmenopausal women.1 The indication in combination with letrozole is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.1 The confirmatory Phase 3 trial, PALOMA-2, is fully enrolled.

Ibrance is the first and only cyclin-dependent kinase 4/6 (CDK 4/6) inhibitor approved by the FDA.

Pfizer Receives Expanded FDA Approval For Ibrance (palbociclib) In HR , HER2- Metastatic Breast Cancer

FDA-approved Alzheimer's medications may help people quit smoking

Despite several safe drug therapies available to help smokers quit, three-quarters report relapsing within six months of a quit attempt. University of Pennsylvania researchers Rebecca Ashare and Heath Schmidt saw potential for a permanent cessation solution in a class of FDA-approved medications used to improve cognitive impairments from Alzheimer's disease.

In a study consisting of a rat trial and a human trial, Ashare and Schmidt studied the effects of two acetylcholinesterase inhibitors, or AChEIs, called galantamine and donepezil on overall nicotine intake. The rat component showed that pretreating the rodents with an AChEI decreased their nicotine consumption. Consistent with these effects, clinical trial participants taking the AChEI, not the placebo, smoked 2.3 fewer cigarettes daily, a 12 percent decrease, and noted feeling less satisfied with the cigarettes they did smoke.

 (Galantamine )  (Donepezil) 

"We're very interested in screening potential efficacy of anti-addiction medications in our models," said Schmidt, a professor in Penn's School of Nursing and Perelman School of Medicine. "For this study, we looked at potential smoking-cessation medications."

The research itself took a translational approach, what Ashare, a professor in Penn Medicine's psychiatry department, calls bi-directional. In other words, the preclinical data informed the clinical study and vice versa.

At Penn's Center for Interdisciplinary Research on Nicotine Addiction, work on smoking cessation has been ongoing since 2001. Specifically, research from Caryn Lerman, CIRNA's director and the Mary W. Calkins Professor in Psychiatry, concluded that ...

FDA-approved Alzheimer's medications may help people quit smoking

No evidence found linking anti-nausea drug to birth defects

No evidence found linking anti-nausea drug to birth defects: No evidence has been found to link the anti-nausea drug Zofran to an increased risk of birth defects. In fact, women with the condition who took Zofran reported fewer miscarriages and pregnancy terminations and higher live birth rates than women with extreme morning sickness who did not take the drug.

Novartis receives FDA Breakthrough Therapy designation for PKC412 (midostaurin)

Novartis announced today that the United States Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to PKC412 (midostaurin). PKC412 (midostaurin) is an investigational treatment for adults with newly-diagnosed AML who are FLT3 mutation-positive, as detected by an FDA-approved test, and who are eligible to receive standard induction and consolidation chemotherapy.

The Breakthrough Therapy designation for PKC412 (midostaurin) is primarily based upon the positive results from the Phase III RATIFY (CALGB 10603) clinical trial. This study was conducted in partnership with the Alliance for Clinical Trials in Oncology and presented during a plenary session at the 57th American Society of Hematology (ASH) Annual Meeting.

Patients who received PKC412 (midostaurin) and standard induction and consolidation chemotherapy experienced a significant improvement in overall survival (OS) (hazard ratio = 0.77, P = 0.0074) compared to those who received standard induction and consolidation chemotherapy alone. The median OS for patients in the PKC412 (midostaurin) treatment group was 74.7 months (95% confidence interval [CI]: 31.7, not attained), versus 25.6 months (95% CI: 18.6, 42.9) for patients in the placebo group. No statistically significant differences were observed in the overall rate of grade 3 or higher hematologic and non-hematologic adverse events in the PKC412 (midostaurin) treatment group versus the placebo group. A total of 37 deaths were reported, with no difference in treatment-related deaths observed between groups.

"For more than 25 years, medical developments have been limited for AML patients and the chemotherapy treatment strategy has essentially remained unchanged," said Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical Affairs. "We look forward to working closely with the FDA to bring PKC412 (midostaurin), the first potential AML targeted therapy, to patients as quickly as possible."

Novartis receives FDA Breakthrough Therapy designation for PKC412 (midostaurin)