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)

Lenalidomide trials show potential for expanding lymphoma, leukaemia indications

Positive findings from two clinical trials have been published for the immunomodulatory agent lenalidomide in patients with heavily pretreated mantle cell lymphoma, and in adults with T-cell leukaemia-lymphoma or peripheral T-cell lymphoma.

The results of the phase II MCL-002 (SPRINT) study suggest that, compared with an investigator's choice of treatment, lenalidomide 25 mg/day on days 1-21 of a 28-day cycle significantly improved progression-free survival (PFS) in patients with relapsed or refractory mantle cell lymphoma who were ineligible for intensive chemotherapy or stem cell transplantation.

After a median of 15.9 months, the 170 lenalidomide-treated patients had a median PFS of 8.7 months compared with 5.2 months in the 84 patients who were treated with single-agent rituximab, gemcitabine, fludarabine, chlorambucil or cytarabine, giving a hazard ratio (HR) of 0.61.

Lenalidomide trials show potential for expanding lymphoma, leukaemia indications