FDA approves non-alcoholic Docetaxel Injection

In continuation of my update on Docetaxel

Teikoku Pharma USA, Inc. ("Teikoku" or "the Company") announced today that the U.S. Food and Drug Administration ("FDA") has approved Docetaxel Injection, Non-Alcohol Formula ("Docetaxel Injection") for the treatment of breast cancer, non-small cell lung cancer, prostate cancer, gastric adenocarcinoma, and head and neck cancer. Teikoku entered into an exclusive licensing agreement with Eagle Pharmaceuticals Inc. ("Eagle Pharmaceuticals") in October 2015 to market, sell and distribute Docetaxel Injection in the U.S.

The main difference, compared to other docetaxel formulations, is that Docetaxel Injection is the first non-alcohol formulation approved in the U.S. Further differentiating it from some of the currently marketed docetaxel formulations is that Teikoku's Docetaxel Injection:

• Requires no prior dilution with a diluent and is ready to add to the infusion solution; and
• Is available in three presentations: 20mg/ml in single-dose vials, and 80 mg/4 mL or 160 mg/8 mL in multiple-dose vials.............

FDA approves non-alcoholic Docetaxel Injection

Teva Pharmaceuticals and Eagle Pharmaceuticals Announce FDA Approval of Bendeka (bendamustine hydrochloride) Injection

Teva Pharmaceutical Industries Ltd. (NYSE:TEVA) and Eagle Pharmaceuticals, Inc. (Nasdaq:EGRX) today announce that the U.S. Food and Drug Administration (FDA) has approved Bendeka, (bendamustine hydrochloride) injection, a liquid, low-volume (50 mL) and short-time 10-minute infusion formulation of bendamustine. Bendeka is approved for the treatment of patients with chronic lymphocytic leukemia (CLL) and for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Efficacy in CLL relative to first-line therapies other than chlorambucil has not been established. “We are thrilled that the FDA has approved Bendeka and are excited for what we believe will be a promising launch with Teva. Importantly, we believe that patients with CLL or indolent B-cell NHL that has progressed will benefit from the multiple administration options this product offers,” said Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

“Teva looks forward to commercializing this new bendamustine product, which we believe represents an important benefit to both patients and healthcare providers,” said Paul Rittman, Senior Vice President and General Manager, Teva Oncology. “We are pleased to add Bendeka to Teva’s Oncology portfolio, and bendamustine franchise, furthering our commitment to enhancing treatment options for patients affected by cancer.”

Bendeka was granted Orphan Drug Designations for both CLL and indolent B-cell NHL.

Under the February 2015 exclusive license agreement for Bendeka, Teva is responsible for all U.S. commercial activities for the product including promotion and distribution. Teva expects to make Bendeka commercially available to prescribers during the first quarter of 2016.

Teva Pharmaceuticals and Eagle Pharmaceuticals Announce FDA Approval of Bendeka (bendamustine hydrochloride) Injection

FDA Approves Bridion (sugammadex) to Reverse Effects of Neuromuscular Blocking Drugs

"Bridion provides a new treatment option that may help patients recover sooner from medications used for intubation or ventilation during surgery,” said Sharon Hertz, The U.S. Food and Drug Administration today approved Bridion (sugammadex) injection to reverse the effects of neuromuscular blockade induced by rocuronium bromide and vecuronium bromide, which are used during certain types of surgery in adults.

Rocuronium bromide and vecuronium bromide are neuromuscular blocking drugs that cause temporary paralysis by interfering with the transmission of nerve impulses to the muscle and are used to paralyze the vocal cords when patients require an artificial airway or breathing tube for surgery, a process called tracheal intubation. They can also be used to prevent patients from moving during surgery while they are receiving general anesthesia. Neuromuscular blocking drugs are also sometimes used to prevent the body from breathing automatically when a patient has to be placed on a ventilator.

M.D., director of the Division of Anesthesia, Analgesia and Addiction Products in the FDA’s Center for Drug Evaluation and Research. “This drug enables medical personnel to reverse the effects of neuromuscular blocking drugs and restore spontaneous breathing after surgery.

FDA Approves Bridion (sugammadex) to Reverse Effects of Neuromuscular Blocking Drugs

FDA Approves Uptravi (selexipag) for Pulmonary Arterial Hypertension

On December 21, the U.S. Food and Drug Administration approved Uptravi (selexipag) tablets to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive, and debilitating rare lung disease that can lead to death or the need for transplantation. “Uptravi offers an additional treatment option for patients with pulmonary arterial hypertension,” said Ellis Unger, M.D., director of the Office of Drug Evaluation I in the FDA’s Center for Drug Evaluation and Research. “The FDA supports continued efforts to provide new treatment options for rare diseases.”

PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath, among other more serious complications.

Uptravi belongs to a class of drugs called oral IP prostacyclin receptor agonists. The drug acts by relaxing muscles in the walls of blood vessels to dilate (open) blood vessels and decrease the elevated pressure in the vessels supplying blood to the lungs.

Uptravi’s safety and efficacy were established in a long-term clinical trial of 1,156 participants with PAH. Uptravi was shown to be effective in reducing hospitalization for PAH and reducing the risks of disease progression compared to placebo. Participants were exposed to Uptravi in this trial for a median duration of 1.4 years.

FDA Approves Uptravi (selexipag) for Pulmonary Arterial Hypertension

FDA Approves Alecensa (alectinib) for ALK-Positive Non-Small Cell Lung Cancer

The U.S. Food and Drug Administration today approved Alecensa (alectinib) to treat people with advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) whose disease has worsened after, or who could not tolerate treatment with, another therapy called Xalkori (crizotinib).

Lung cancer is the leading cause of cancer death in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. An ALK (anaplastic lymphoma kinase) gene mutation can occur in several different types of cancer cells, including lung cancer cells. ALK gene mutations are present in about 5 percent of patients with NSCLC. In metastatic cancer, the disease spreads to new parts of the body. In ALK-positive NSCLC metastatic patients, the brain is a common place for the disease to spread.

“Today’s approval provides a new therapy for a group of patients who would have few treatment options once their disease no longer responds to treatment with Xalkori,” said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand.”

Alecensa is an oral medication that blocks the activity of the ALK protein, which may prevent NSCLC cells from growing and spreading.

The safety and efficacy of Alecensa were studied in two single-arm clinical trials of patients with metastatic ALK-positive

FDA Approves Alecensa (alectinib) for ALK-Positive Non-Small Cell Lung Cancer

FDA Approves Zurampic (lesinurad) to Treat High Blood Uric Acid Levels Associated with Gout

The U.S. Food and Drug Administration today approved Zurampic (lesinurad) to treat high levels of uric acid in the blood (hyperuricemia) associated with gout, when used in combination with a xanthine oxidase inhibitor (XOI), a type of drug approved to reduce the production of uric acid in the body. Gout is a painful form of arthritis caused by the buildup of too much uric acid in the body, and usually appears first as redness, soreness, and swelling in the big toe. Uric acid in the blood is produced by the breakdown of substances called purines, which are found in all the body’s tissues. Uric acid usually dissolves in the blood then passes through the kidneys and out of the body in urine. Uric acid can build up in the blood, a condition called hyperuricemia. This occurs when the body increases the amount of uric acid it makes, the kidneys do not get rid of enough uric acid, or a person eats too many foods high in purines. Most people with hyperuricemia do not develop gout, but if uric acid forms crystals in the body, gout can develop.

"Controlling hyperuricemia is critical to the long-term treatment of gout," said Badrul Chowdhury, M.D., director of the Division of Pulmonary, Allergy and Rheumatology Products in the FDA’s Center for Drug Evaluation and Research. "Zurampic provides a new treatment option for the millions of people who may develop gout over their lifetimes."

Zurampic works by helping the kidney excrete uric acid. It does this by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney.

The safety and efficacy for Zurampic were evaluated in three randomized, placebo-controlled studies in combination with a XOI involving 1,537 participants for up to 12 months. Participants treated with Zurampic in combination with a XOI experienced reduced serum uric acid levels compared to placebo.

FDA Approves Zurampic (lesinurad) to Treat High Blood Uric Acid Levels Associated with Gout

New type of hydrogen bond discovered

An entirely new class of hydrogen bond that forms between a boron–hydrogen group and the aromatic, π-electron system of a benzene ring has been discovered. The non-classical B–H…π bond can be seen in the gas phase locking together diborane and benzene with a strength comparable to the hydrogen bonds that hold water dimers together

New type of hydrogen bond discovered 

EMA CHMP considers AcelRx's ARX-04 for acute pain treatment for centralized review

AcelRx Pharmaceuticals, Inc. (Nasdaq: ACRX), a specialty pharmaceutical company focused on the development and commercialization of innovative therapies for the intended treatment of acute pain, reported that the Committee for Medicinal Products for Human Use (CHMP) at the European Medicines Agency (EMA) has confirmed that a Marketing Authorization Application (MAA) for ARX-04 may be submitted in the European Union (EU) under the Agency's centralized procedure. ARX-04 (sufentanil sublingual tablet, 30 mcg) is being developed for the treatment of moderate-to-severe acute pain in adult patients administered by a healthcare professional in a medically supervised setting.

ARX-04 is a non-invasive, fast-onset sufentanil product candidate under investigation.

"We appreciate the CHMP's consideration of ARX-04 for regulatory review under the centralized process, which we expect will make our planned MAA filing with the EMA much more efficient," commented Dr. Pamela Palmer, co-founder and chief medical officer of AcelRx. "The EMA's centralized procedure is typically limited to products the EMA believes constitute significant therapeutic, scientific or technical innovations, characteristics we believe ARX-04 possesses."

For eligible drugs, the centralized procedure permits the submission of a single marketing application to the EMA that, if approved, allows the drug to be marketed in all 27 EU member states, as well as in the three European Economic Area (EEA) countries: Iceland, Liechtenstein and Norway.

ARX-04 is currently being studied in an open-label Phase 3 study (SAP302) in adult patients who present in the emergency room with acute moderate-to-severe pain associated with trauma or injury, and an additional Phase 3 study (SAP303) is planned in postoperative patients with acute moderate-to-severe pain. An earlier Phase 3 trial (SAP301) in patients with acute moderate-to-severe pain following ambulatory abdominal surgery demonstrated that patients administered ARX-04 experienced significantly greater pain relief compared to those receiving placebo, as measured by the time-weighted summed pain intensity difference over the first 12 hours of treatment (SPID12) (p<0.001). AcelRx expects to file marketing applications to both the EMA and the U.S. Food and Drug Administration (FDA) for ARX-04.

EMA CHMP considers AcelRx's ARX-04 for acute pain treatment for centralized review

Opicapone simplifies levodopa-related motor fluctuation treatment

Once-daily opicapone is effective for the treatment of end-of-dose motor fluctuations in patients receiving levodopa for Parkinson’s disease, phase III study findings show.

The results indicate that at a dose of 50 mg/day the drug, a potent third-generation catechol-O-methyltransferase (COMT) inhibitor, was superior to placebo and non-inferior to entacapone (200 mg with each levodopa dose) in reducing the absolute time patients spent in the off state.

The magnitude of effect with opicapone was greater that than of entacapone, with a 26.2 minute greater reduction in the time spent in the off state after 14–15 weeks of treatment and a 60.8 minute greater reduction compared with placebo.

Opicapone 50 mg “is, therefore, the only once-daily COMT inhibitor to provide a mean reduction in time in the off state that is clinically relevant,” say Patrício Soares-da-Silva (BIAL, Coronado, Portugal) and team.

The average changes from baseline in time spent in the off state over a 24-hour period were 116.8 minutes in 115 patients taking opicapone 50 mg/day, 96.3 minutes in 120 patients taking entacapone and 56.0 minutes in the placebo group.

Opicapone 25 mg and 5 mg were also tested in 116 and 119 patients, respectively, but the effects of these doses on the time patients spent in the off state did not differ significantly from that of placebo.

The researchers note in The Lancet Neurology that, in addition to greater reductions in the time patients spent in the off state, opicapone 50 mg was associated with greater increases in the percentage of time patients spent in the on state without troublesome dyskinesia, with a 5.4% difference compared with placebo and a 1.2% difference compared with entacapone.

Improvements in global symptoms were seen in significantly more patients taking opicapone 50 mg than in those taking entacapone, and while numerical improvements in motor symptom scores were seen in all groups, differences between active treatment and placebo groups were not significant.

Opicapone simplifies levodopa-related motor fluctuation treatment

Selexipag holds promise for treatment of pulmonary hypertension

Living with pulmonary arterial hypertension is challenging, but the chore of treating the rare heart disease may change following promising clinical trial data to be published in the Dec. 24 issue of the New England Journal of Medicine.

Data from the largest study ever of pulmonary hypertension shows the oral medication Selexipag led to a 40 percent reduction in hospitalizations and worsening symptoms among patients with pulmonary hypertension.

Selexipag targets a well-known disease pathway that opens blood vessels to the lungs and improves heart function and is easier to use than PH treatments delivered with infusions or injections.

"For more than two decades we've targeted the prostacyclin pathway to induce vasodilation in these blood vessels in the lung," says senior study author Vallerie McLaughlin, M.D., director of the University of Michigan Pulmonary Hypertension Program.

"But because of the cumbersome nature of treatment, patients would often wait until late stages to begin therapy. Having an oral medication to attack the disease pathway will be a major advancement because less ill patients will be willing to begin this therapy," McLaughlin says.

Selexipag demonstrated effectiveness while its most frequent adverse events were headache, diarrhea, nausea, muscle pain and joint pain. The side effects were considered consistent with prostacyclin therapy.

The medication is not commercially available. Following the phase 3 clinical trial, the U.S. Food and Drug Administration is evaluating the drug.

Pulmonary hypertension, which is high blood pressure in the loop of blood vessels connecting the heart and lungs, can make everyday activities exhausting. It often leads to life-threatening heart failure as the heart works harder to pump blood to the lungs.

The greatest number of cases is reported in women between ages 21 and 40 who most often experience fatigue and shortness of breath.

While a rare disease, research of causes and treatment of pulmonary hypertension is growing. The GRIPHON study is a standout because of its size and scope, enrolling 1,156 patients with pulmonary hypertension from 181 centers from 39 countries in North and South America, Europe, Asia-Pacific and Africa.

Selexipag holds promise for treatment of pulmonary hypertension