Pharmaceutical News

FDA approves Chelsea Therapeutics drug for low blood pressure

Chelsea Therapeutics International Ltd’s drug Northera, which treats a rare form of low blood pressure associated with neurological disorders such as Parkinson’s disease, has won U.S. approval, the Food and Drug Administration said on Tuesday.

The company’s shares rose 34 percent to $6.63 in after-market trading.

The drug’s label will carry a boxed warning, the most serious possible, of the risk of supine hypertension, or increased blood pressure while lying down, a danger that can cause stroke.

In January, an advisory panel to the FDA recommended approval but also suggested the company conduct a follow-up study to prove durable benefit. Panelists said gaps in clinical data made it hard to determine whether Northera, which appears effective after a week’s treatment, is effective over the long term.

The FDA followed the recommendation and approved the drug on an “accelerated” basis. This allows for approval a drug to treat a serious disease based on an intermediate measure while the company conducts more trials.

In the meantime, the FDA said, “it is essential that patients be reminded that they must sleep with their head and upper body elevated. Supine blood pressure should be monitored prior to and during treatment and more frequently when increasing doses.”

Chelsea first filed for approval of Northera in 2011. The FDA rejected the drug in 2012 and asked for additional data. The company is also testing the drug, known generically as droxidopa, in mid-stage studies to treat fibromyalgia and intradialytic hypotension.

Source: yahoo news

 

Lilly lung cancer drug improves survival in late-stage trial

An experimental cancer drug developed by Eli Lilly and Co, touted by some to be the company’s next blockbuster, significantly improved survival rates in lung cancer patients, sending the company’s shares up 3 percent in early trading.

Lilly needs new drugs to offset declining sales of its older drugs as they lose patent protection.

Ramucirumab, designed to treat multiple cancers, has the potential to generate annual sales of $1.5 billion by 2020, according to some analysts.

The drug has already been shown be successful in treating stomach cancer, and Lilly is waiting for approval from the U.S. Food and Drug Administration to market it for that disease.

The latest results could help allay some concerns about the drug after it failed to delay the progression of breast cancer in a late-stage trial last year.

The late-stage lung cancer trial compared a combination of ramucirumab and a common chemotherapy drug, docetaxel, with a combination of a placebo and docetaxel in treating patients with non-small cell lung cancer.

The trial, known as Revel, showed that ramucirumab significantly improved overall survival rates as well as improving survival rates without the cancer worsening.

Lilly did not provide details of the trial results, which it said would be presented at a scientific meeting.

The company said on Wednesday that it planned to submit the first application for marketing approval later this year.

Data from two other studies to test the drug’s effectiveness to treat liver and colorectal cancer are expected later this year, Lilly said.

BMO Capital Markets analyst Alex Arfaei expressed caution about the latest results.

“We believe Revel needs to show at least (a) 2-3 month improvement in overall survival to be considered clinically meaningful,” he said in a note.

Ramucirumab, which Lilly acquired through its $6.5 billion purchase of ImClone Systems Inc in 2008, works by blocking development of blood vessels that feed tumors – a process known as angiogenesis.

Source: Fox news

Promising class of antibiotics discovered for drug-resistant TB

St Jude Children’s Research Hospital scientists have discovered a promising new class of antibiotics that could aid efforts to overcome drug-resistance in tuberculosis (TB). The drugs increased survival of mice infected with TB and were effective against drug-resistant strains of TB. St Jude led the international research effort, results of which appear in the journal Nature Medicine.

The antibiotics, called spectinamides, were created by changing the chemical structure of an existing antibiotic, spectinomycin, which does not work against TB.

In multiple trials of mice with both active and chronic TB infections, researchers report that one version of the new drug—an analogue known as 1599—was as good as or better than current TB drugs at reducing levels of the bacteria in the lungs of mice. In addition, 1599 caused no serious side effects.

“This study demonstrates how classic antibiotics derived from natural products can be redesigned to create semi-synthetic compounds to overcome drug resistance,” said corresponding author Richard Lee, a member of the St Jude Department of Chemical Biology and Therapeutics. “I hope the result will be drugs that are more effective against tuberculosis and offer a faster route to a cure with fewer side effects.”

TB remains a leading cause of global illness and death. The latest data from the World Health Organization estimates that TB kills 1.3 million persons annually and sickens 8.6 million worldwide. Current treatment requires months of multi-drug therapy to eradicate the slow-growing bacterium, which can lie dormant for years without causing symptoms and results in hard to treat chronic or latent infections. The rise of multi-drug resistant TB, including strains reportedly resistant to all available medications, has further complicated treatment.

This new class of antibiotics works against TB by disrupting the function of a part of the cell known as the ribosome, which is responsible for protein synthesis. To do that, the spectinamides bind to a particular site on ribosomes that is not shared by other TB drugs. That allows the drug to be used in combination with other medications.

For this study, researchers used an approach called structure-based design to re-engineer how spectinomycin binds to the ribosome. To guide their design efforts, scientists used a 3-D model that provided an atomic-level view of spectinomycin bound to the tuberculosis ribosome. The study reinforces the potential of structure-based design as a tool for designing other new agents to block mechanisms TB and other bacteria use to resist current antibiotics, Lee said.

The research reports on the first 20 of the more than 120 spectinomycin derivatives that have resulted from the effort. The list includes 1599 and two other analogues tested against TB in mice.

The three analogues not only bound the ribosome tightly, but they were more successful at avoiding a TB resistance mechanism called efflux. The TB bacteria use efflux pumps as a strategy to remove drugs and other threats from the cell before they can work against the bacteria. Efflux pumps, however, did not protect TB against spectinamides.

The drugs were also effective against multi-drug-resistant strains of TB growing in the laboratory. The strains had been isolated from patients with the disease.

Researchers also found no evidence that 1599 or the two other analogues tested interfered with normal functioning of human cells. Preliminary safety testing on cells grown in the laboratory showed the drugs were not toxic to mammalian cells because they only inhibit the bacterial ribosomes and not mammalian ribosomes.

Work is underway now in mice combining 1599 with new or existing TB drugs. The goal is to identify multi-drug therapy to try in a clinical trial of patients with drug-resistant TB.

Source: India medical Times

Oral insulin capsule trial a success, company says

Israel’s Oramed, which is racing Novo Nordisk of Denmark to develop the world’s first insulin pill, moved a step closer to its goal on Thursday by announcing successful results from a small mid-stage test.

The oral drug delivery specialist said its insulin capsule had met all primary and secondary endpoints in a Phase IIa clinical trial and it now plans to launch a larger mid-stage study in the third quarter.

Shares in the Nasdaq-listed company opened 10 percent higher at $28.50 on the news. The stock has surged from around $4 since the end of 2012 on rising hopes for its insulin pill.

The concept of oral insulin as a way to relieve diabetics of several daily injections has been around since the 1930s, but making it a reality is extremely difficult because insulin is destroyed by enzymes in the digestive system.

Oramed believes that it has now found a solution to allow enough insulin to survive the onslaught of digestive juices to still do some good.

At least 90 percent of the more than 382 million diabetes sufferers worldwide are in the type 2 category, according to the International Diabetes Foundation, which expects the number of diabetes patients to near 600 million by 2035.

Consensus analyst forecasts suggest that the overall diabetes drug market, worth $37 billion a year at present, will reach more than $57 billion by 2018, according to Thomson Reuters Pharma.

Oral insulin could make it easier for sufferers to start early treatment, slow progression of the disease and delay the need for injections, Oramed said. Unlike injections, the ingested form passes first into the liver, which regulates the secretion of insulin into the bloodstream.

The new year-long Phase IIb study in the United States will study 150 type 2 diabetes patients and mainly test for the drug’s effectiveness, Chief Executive Nadav Kidron told Reuters after the company issued results of the Phase IIa trial.

During the Phase IIa trial, conducted under a new U.S. Food and Drug Administration (FDA) drug protocol, 30 patients with type 2 diabetes entered an in-patient setting for one week.

“The FDA wanted us to show one thing – that it was safe so they will let us do a IIb trial,” Kidron said.

While Oramed was not checking for efficacy, Kidron said the IIa trial revealed that it was effective, though the sample size was too small for FDA purposes.

Oramed will also need to conduct a final large-scale Phase III trial before the drug is licensed for sale, so the capsule is still years away from hitting the market.

The company is, however, ahead of Novo Nordisk, which has yet to start Phase II testing.

Oramed is hoping to partner with large pharmaceutical firms for development and sales of the drug. But Kidron said that only preliminary discussions have taken place so far.

The company also plans to initiate a Phase IIa FDA study for type 1 diabetes in the near term.

The global expense for diabetes is about $500 billion and an oral version could bring a large drop in costs.

Oramed noted that the pill would not eliminate the eventual need for injections but could delay the shift to needles by many years.

Source: Yahoo news

Anti-VEGF drugs making a difference in vision, longterm care

eye

A treatment introduced less than 10 years ago has already made a difference in the number of Americans losing their vision and being admitted to nursing homes, according to a new study.

Two Duke University economists looked at Medicare beneficiaries with so-called “wet” macular degeneration and found those diagnosed after the introduction of anti-VEGF drugs were less likely to go blind and less likely to move into long-term care.

“At last we have found a way of managing this horrible and very common disease among the oldest of the old,” said Frank Sloan, who led the new study.

Age-related macular degeneration (AMD) is the number one cause of blindness in the U.S. affecting older adults, usually after age 65. Most AMD patients have the dry form of the disease, but about 10 percent have wet AMD, which progresses more quickly than the dry form.

Past treatments weren’t very effective at managing wet AMD, but retinal surgeons began using injections of vascular endothelial growth factor inhibitors, known as anti-VEGF, in the mid 2000s.

Previous clinical research has indicated that anti-VEGF treatments are effective for wet AMD, but Sloan said those types of studies don’t let you see longer-term outcomes or how well the therapy works in a real-world setting.

The researchers used Medicare claims information from 1994 to 2011 to examine the vision outcomes and long-term care facility admissions of wet AMD patients who were treated with older methods or with the new anti-VEGF drugs.

The two most commonly used drugs, ranibizumab (Lucentis) and bevacizumab (Avastin), were introduced for eye therapy in 2006.

The researchers discovered that the use of anti-VEGF therapy reduced vision loss by 41 percent and the onset of severe vision loss and blindness by 46 percent, compared to earlier forms of treatment.

They also found that patients who received anti-VEGF were 19 percent less likely to be admitted to long-term care facilities during a two-year follow-up period compared to those treated before the drugs came into use.

The findings were published in JAMA Ophthalmology.

The new treatments may be changing the way some doctors think about wet AMD.

“We used to say it was better to have the dry form because it tended to be milder and slowly progressive as opposed to the wet AMD, which has a rapid onset and much more severe vision loss,” Dr. Michael Stewart told Reuters Health.

Stewart, who chairs the ophthalmology department at the Mayo Clinic in Jacksonville, Florida, was not involved in the new study.

Stewart said results like these actually call into question whether or not that old statement is still true because the anti-VEGF drugs are so effective.

“By and large, we are maintaining good vision in most people that we treat,” Stewart said.

Stewart also says the new drugs have revolutionized the way retinal surgeons approach these patients.

He says that early diagnosis with quick initiation of treatment is the best way of preserving vision. The typical course of treatment is to give an injection of the drug in to the eye, about one time per month, but treatment can be tapered to the patients’ needs.

“Patients and family – and most of us, actually – think of a needle in the eye as one of the worst medical procedures we can imagine,” Stewart said, “but the reality is patients tolerate them very, very well and very few patients actually forgo the treatment because of either imagined or real pain, discomfort and anxiety.”

Source: Reuters

FDA: Aleve may be safer on heart than other drugs

Federal health officials say the pain reliever in Aleve may be safer on the heart than other popular anti-inflammatory drugs taken by millions of Americans.

A Food and Drug Administration review posted online Tuesday said naproxen — the key ingredient in Aleve and dozens of other generic pain pills — may have a lower risk of heart attack and stroke than rival medications like ibuprofen, sold as Advil and Motrin. FDA staffers recommend relabeling naproxen to emphasize its safety.

The safety review was prompted by a huge analysis published last year that looked at 350,000 patients taking various pain relievers. The findings suggest naproxen does not carry the same heart risks as other medications in the class known as nonsteroidal anti-inflammatory drugs, or NSAIDs.

The agency released its memo ahead of a public meeting next month where outside experts will discuss the new data and whether naproxen should be relabeled. The agency is not required to follow the group’s advice, though it often does.

If ultimately implemented, the labeling changes could reshape the multibillion-dollar market for drugs used to treat headaches, muscle pain and arthritis.

The change could make Aleve and other naproxen drugs the first choice for patients with a higher risk for heart problems, according to Ira Loss, a pharmaceutical analyst with Washington Analysis. But he added that all NSAIDs will continue to carry warnings about internal bleeding and ulceration, a serious side effect that is blamed for more than 200,000 hospital visits every year.

Source: nbc news

Think twice before giving your child paracetamol!

A new study has found that paracetamol can interfere with the brain development of children, and can even be dangerous for unborn kids.

Researchers at Uppsala University examined paracetamol, one of the most commonly used drugs for pain and fever in children, by giving small doses of it to ten-day-old mice. They later carried out tests on the behavioral habits of the mice in adulthood.

They found that the mice could be hyperactive in adulthood, could display behavioural disturbances, and could have lower memory capability compared to the mice that weren’t given the dose, the Local reported.

Researchers said that the exposure to and presence of paracetamol during a critical period of brain development can induce long-lasting effects on cognitive function and alter the adult response to paracetamol in mice.

They added that parents should be careful in administering the drug. (Read: Why you don’t need medicine every time you have slight fever)

Researcher Henrik Viberg told the Upsala Nya Tidning newspaper that this shows that there are reasons to restrict the use of paracetamol at the end of pregnancy and to hold back from giving the medicine to infants.

The study was published in the online Toxicological Sciences journal.

So when should I take antipyretics like Paracetamol?

Fever up to 38 degree (102° F) might be considered as a safe, beneficial level that should not be interfered with antipyretics every time. Antipyretics should be used only when the temperature of the body is raised high enough to cause discomfort. In general, body temperature between 102° F and 104°F may cause uneasiness, so it’s better to bring it up to or below 102° F. Fever that rises above 104° F is definitely harmful and should be reduced with quick action. (Read: Apollo Hospitals launches fever clinic to tackle recurring, unknown fevers)

Adverse effects

The use of antipyretics to reduce fever is still controversial. Since all the available anitipyretics are pretty effective in managing fever, safety should be the main criteria while taking them. Common side-effects of frequent use of antipyretics include nausea, vomiting, stomach ache, breathing difficulties and headache. (Read: Painkillers or analgesics: Side-effects and precautions)

Most adverse effects due to antipyretics are a result of overdose (due to ignorance and negligence). Most of them have been cited in western literature and therefore may differ from Indian population. Overdose of paracetamol use has shown to cause liver toxicity and may also have an effect on circadian rhythm in healthy individuals. Ibuprofen is may lead to digestive disorders and, rarely, gastrointestinal bleeding. Kidney insufficiency and gastritis are also known adverse effects of antipyretics. (Read: Ibuprofen — why you shouldn’t pop these pills indiscriminately)

To summarize, antipyretics should not be used to bring down fever completely. The use of antipyretics should be limited just for symptomatic relief and to ensure that it is not raised to a dangerous level. Most of the times people also use antipyretics when there is minimal fever or to prevent fever from recurring. However, there is no evidence suggesting that antipyretics prevent fever from recurring. Also, half of times the dosage taken is incorrect. With this the chances of toxicity and adverse effects increase. Therefore, it is better to check the labels before taking an antipyretic drug and think about the long term complications you might have to face.

source: newsr

New drug may stop spread of breast cancer

Researchers have identified a new compound that completely halts the spread of metastatic breast cancer in mice.

The vast majority of deaths from cancer result from its progressive spread to vital organs such as the brain and lungs – a process known as metastasis.

In a recent series of studies researchers identified a previously unknown critical role for a potential cancer causing gene, Bcl3, in metastatic breast cancer.

“We showed that suppressing this gene reduced the spread of cancer by more than 80 per cent,” said Dr Richard Clarkson from Cardiff University’s European Cancer Stem Cell Research Institute.

“Our next goal was to then find a way to suppress Bcl3 pharmacologically. Despite great improvements in therapy of early stage breast cancer, the current therapeutic options for patients with late stage metastatic disease are limited.

“There is therefore a clear unmet clinical need to identify new drugs to reverse or at least to slow down disease progression,” he added.

Clarkson and his team joined up with researchers Dr Andrea Brancale and Dr Andrew Westwell from the Cardiff University School of Pharmacy and Pharmaceutical Sciences, to develop small chemical inhibitors of the Bcl3 gene.

Computer aided modelling of how the Bcl3 gene functions inside the cell allowed the group to identify a pocket on the surface of Bcl3 essential for its function.
By screening a virtual compound library for chemicals that could fit inside this pocket, using state-of-the-art computer software, they identified a drug candidate that potently inhibits Bcl3.

The compound was then trialled on mice with metastatic disease. The resulting effect was that the drug completely inhibited the development of the mice’s metastatic tumours.
Researchers are now working to conduct clinical trials of the compound. The aim is to develop a therapeutic agent capable of blocking metastatic disease in breast cancer and a variety of tumour types.

Source: Business Standard

A pill ‘melts away’ common form of leukaemia

Use of a twice-daily pill could turn a deadly blood cancer into a highly treatable disease, according to scientists at Weill Cornell Medical College who led a multinational research team.

Their findings on the therapy for chronic lymphocytic leukaemia (CLL), reported in the New England Journal of Medicine, suggest that patients may be able to avoid having to take debilitating chemotherapy.

CLL is the most common form of leukaemia, a cancer of the white blood cells. Some 16,000 Americans are diagnosed with CLL annually, and about 5,000 die of it each year.

“The treatment today for CLL can be worse than the disease, leading to a great deal of side effects and death. This study, and others we have conducted on idelalisib, demonstrates that we may no longer need to use chemotherapy in CLL,” says the lead investigator, Dr Richard R Furman, the Richard A Stratton Associate Professor in Haematology and Oncology at Weill Cornell Medical College and a haematologist/oncologist at New York-Presbyterian/Weill Cornell Medical Centre. “Even if this cancer remains incurable, it now can be treated as if it was a chronic disease with a pill, in the same way that high blood pressure is treated.”

CLL is a cancer of B cells, which normally produce antibodies to fight infections. In CLL, B cells grow out of control, accumulating in all of a patient’s organs. Patients are typically treated with a combination of chemotherapeutic drugs, to which they commonly respond. Unfortunately, patients ultimately relapse and require repeated cycles of chemotherapy. With each relapse, the remissions become shorter until the patient either no longer responds, or is forced to stop taking the drugs because of their side effects, which are a result of the medications’ inability to differentiate between healthy cells and cancer cells.

In this randomized, double-blinded study, researchers from 19 medical centres in five countries tested a combination of two targeted drugs – medications that attack cancer without damaging healthy cells. They compared rituximab and idelalisib against rituximab and a placebo pill in 220 CLL patients who could not receive chemotherapy.

They found that those who received the combination of idelalisib and rituximab went longer without their disease worsening than those who received only rituximab, which has been the standard of care. Six months into the study, cancers in 93 per cent of participants in the combination therapy group had not worsened, compared to 46 per cent of those in the rituximab plus placebo group.

What’s more, just 13 per cent of patients treated with rituximab alone responded to the therapy, compared to 81 per cent of the participants in the idelalisib treatment group. A higher percentage of patients who received both drugs – some 92 per cent – were still alive a year after the study began, compared to 80 per cent of those who only received rituximab. About the same percentage of patients in each group suffered side effects from the treatments.

The contrast was so significant that an independent data-monitoring committee halted the study early, in October 2013, so that all of the study participants could receive idelalisib.

“We saw incredible responses in patients who used idelalisib. Their cancer quickly melted away,” says Dr Furman, who is also director of Weill Cornell’s CLL Research Centre and an associate professor of medicine. “These types of responses were even seen in patients who didn’t respond to chemotherapy.”

Chemotherapy-resistant patients are typically the most difficult patients to treat. “It is remarkable how quickly idelalisib worked in this heavily treated group of patients, many of whom were resistant to chemotherapy. We saw responses within a week,” Dr Furman says.

Previous studies led by Weill Cornell Medical College have shown equally significant results in newly diagnosed CLL patients and in those who could tolerate chemotherapy.

“Having a treatment like idelalisib, which is highly effective and well tolerated, and thus can generate responses in patients that are unable to tolerate treatment and unlikely to respond, indicates the potential for idelalisib in all patients,” Dr Furman says.

Idelalisib is the second targeted drug that Dr Furman has tested that shows strong activity against CLL. He also studied ibrutinib in a phase 2 clinical trial reported last July in the New England Journal of Medicine. Both drugs, known as tyrosine kinase inhibitors, work on different targets within the same molecular pathway.

Ibrutinib was approved for use in mantle cell lymphoma (another B cell lymphoma) in November by the US Food and Drug Administration. Because it targets B cells, Dr Furman is using the drug as a first-line treatment for all of his CLL patients — even those who are newly diagnosed. “I am now able to avoid all use of chemotherapy in these patients, which has long been my goal,” he says.

Dr Furman believes idelalisib and ibrutinib will become the treatments of choice for all B cell lymphomas. “These drugs will change the lives of many patients,” he says. “Given the long-term toxicities of chemotherapy, leading to bone marrow failure, infections, and death, moving this therapy up front in the treatment algorithm and providing it to all patients is the next step.”

The study was funded by Gilead, for which Dr Furman has served as an advisor.

Source: India Medical Times

GSK’s diabetes drug set for European approval

GlaxoSmithKline said on Friday European regulators had given the green light to its once-weekly diabetes drug albiglutide, which it is marketing as Eperzan.

Albiglutide belongs to the same class of injectable GLP-1 drugs as Victoza, from Novo Nordisk, and Byetta and Bydureon, from Bristol-Myers Squibb and AstraZeneca.

A positive recommendation for a drug by the European Medicines Agency is generally followed by a marketing authorization by the European Commission. GSK said a final decision was anticipated later this quarter.

Last year regulators in the United States pushed back an approval decision on the drug until April 15.

Source: Reuters