‘Game changing’ new lung cancer drug is available from today

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Vaccine trains the body to single out diseased cells that experts say will double survival rates

Lung cancer patients are to be offered a ‘game-changing’ treatment that trains the body to single out and attack diseased cells. It is being made available under a Government policy that enables life-saving treatments to be fast-tracked through the licensing process that usually takes years. Administered in a vaccine every two weeks, the drug nivolumab works by teaching the body’s immune system to attack cancerous cells.

Evidence shows the effect continues for several years after the treatment has stopped. Experts have hailed such immunotherapy as a ‘new era’ in the fight against cancer. Early trials have suggested it doubles survival rates. From today, doctors will be able to offer nivolumab free to patients with advanced lung cancer, for whom surgery is no longer an option. The costs will be footed by the manufacturer, Bristol-Myers Squibb. The therapy differs from ‘blanket’ treatments such as chemotherapy and radiotherapy which kill all cells including healthy ones.

This means there are fewer debilitating side effects such as fatigue, sickness, hair loss and infections caused by healthy cells being destroyed. Some skin cancer patients previously diagnosed as terminal have been able to return to work following immunotherapy. They only need to top up jabs every few months. Lung cancer is one of the deadliest forms of the illness. Only 5 per cent of patients are still alive ten years after diagnosis. It is also the second most common – after breast in women and prostate in men – with 43,000 new cases each year. Nivolumab is the third treatment made available through the Early Access To Medicines Scheme which bypasses red tape that can last up to a decade. Manufacturers submit data on new drugs to experts at the Medicines and Healthcare Products Regulatory Agency for assessment.

If the watchdog is satisfied the treatment can be beneficial without causing harm, it is made available to patients. Costs are covered by the manufacturer until the drug is formally licensed in the usual way. The scheme means patients are effectively guinea pigs testing out new drugs and possible side effects, but the Government hopes it will save hundreds of lives. George Freeman, Life Sciences Minister, said: ‘The positive scientific opinion of nivolumab offers real hope to those who need it most… I hope this is just one of many drugs that will be made available.’

A trial involving 272 patients found 42 per cent taking nivolumab were alive a year later, compared with just 24 per cent who had chemotherapy. Some of those on the drug are still living two years on. Dr Tom Newsom-Davis, consultant cancer specialist at Chelsea and Westminster Hospital, said: ‘Lung cancer is one of the most difficult to treat … early access to nivolumab is therefore very positive … patients have the potential to access a new medicine which has shown in clinical studies to offer significant extension of survival.’ Manufacturers say 10,000 UK patients could benefit from the jab. Last month experts said immunotherapy was a ‘game-changer’ and the biggest breakthrough since chemotherapy.

By Sophie Borland Health Correspondent

FDA provides safety update about Essure Birth Control Implant

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The FDA first announced their intention to provide a safety update about Essure late yesterday evening. Today’s much anticipated report comes on the heals of a private citizen petition that raised serious concerns about the Essure Birth Control Implant and resulted in the launch of an FDA investigation into the birth control device.

This afternoon the U.S. Food and Drug Administration (FDA) added a page to their website informing the public of increased risks associated with the Essure Permanent Birth Control Implant. The new page acknowledges the 5,093 adverse events that have been reported to the agency about Essure and provides new information about serious risks associated with the device including: pelvic pain, migration of Essure coils, perforation of the uterus or fallopian tubes, and rash and itching. The page also advises physicians to warn patients about complications that have resulted in women with nickel allergies who have received the Essure Birth Control Implant.

One section of the webpage recognizes reports of miscarriage and ectopic pregnancy following the non-surgical sterilization procedure, stating, “The FDA will continue to monitor the safety of Essure to make certain that its benefits of providing women with a non-incisional sterilization choice continue to outweigh its risks,” and “While scientific evidence shows that Essure is a highly effective means of sterilization when health care providers and patients follow the appropriate instructions for use, no form of birth control is 100% effective.”

The FDA announced today that there will be a public meeting of their Obstetrics and Gynecology Devices Panel later this year on September 24, 2015, to discuss the safety and efficacy of the device.

Source: Arentz Law Group

China rejects patent linked to Gilead hepatitis C drug

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China has rejected a Gilead Sciences Inc patent application related to its costly hepatitis C drug, a U.S. advocacy group said, adding the move may lead to other countries to consider rejecting patents for the controversial treatment.

Gilead has drawn fire for the cost of its top-selling drug Sovaldi, priced at $1,000 per pill in the United States or $84,000 for a typical 12-week course and its patents have been challenged in the U.S., India and Europe.

The application China has rejected was for a so-called prodrug, the inactive form of the drug which then converts into the chemically active compound once in the body, the New York-based Initiative for Medicines, Access & Knowledge (I-MAK) said.

Gilead, however, holds the China patent to the base compound in the drug, also known by its generic name sofosbuvir and China’s rejection of the prodrug patent does not open the way for copycat drugs to be made in the world’s No. 2 drug market.

China-based officials for Gilead were not immediately available for comment. Emails and calls to Gilead’s U.S. offices outside office hours went unanswered.

Officials at China’s State Intellectual Property Office did not confirm the decision when contacted by Reuters, but a notice posted on the body’s website said Gilead’s application for “nucleoside phosphramidates”, a kind of prodrug, had recently been rejected.

China’s move follows a decision by India’s patent office in January to reject Gilead’s patent application for Sovaldi, finding it was not inventive enough. Gilead is appealing the ruling.

Under pressure to cut prices, the California-based firm agreed last year to make the drug available for lower prices in 91 developing countries.

I-MAK has brought legal challenges against Gilead’s patents or patent applications in five countries not covered by the agreement: China, Argentina, Brazil, Russia and Ukraine.

Charities in Europe have also challenged Gilead’s patent over its prices.

The World Health Organization says as many as 150 million people worldwide live with chronic hepatitis C infection, most of them in low and middle-income countries. It recently added Sovaldi to its essential medicines list and urged lower prices, especially in middle income countries.

By Brendan Pierson and Adam Jourdan, Reuters

(Editing by David Gregorio and Edwina Gibbs), Reuters

Merck seeks FDA approval for grazoprevir / elbasvir to treat HCV GT1, 4 or 6

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Merck is seeking approval from the US Food and Drug Administration (FDA) for its grazoprevir / elbasvir (100mg/50mg), an investigational once-daily, single tablet combination therapy to treat adult patients with chronic hepatitis C genotypes (GT) 1, 4 or 6 infection.

The company has submitted a new drug application (NDA) to the FDA for the drug and is planning to submit additional licence applications in the European Union and other markets by the end of this year.

Grazoprevir / elbasvir is an investigational and once-daily single tablet regimen that includes grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A replication complex inhibitor).

Under the firm’s broad clinical trials programme, grazoprevir / elbasvir is being studied in multiple HCV genotypes and in patients with difficult-to-treat conditions such as HIV / HCV co-infection, advanced chronic kidney disease, inherited blood disorders, and liver cirrhosis, as well as those on opiate substitution therapy.

Merck Research Laboratories clinical development senior vice-president Dr Roy Baynes said: “Merck’s submission is based on evidence from our wide-ranging clinical programme assessing the efficacy and tolerability profile of grazoprevir/elbasvir in populations with chronic hepatitis C.

“This submission to the US FDA is an important milestone as we seek to provide patients with a new treatment option for this serious infection.”

The NDA was submitted based on data from the pivotal C-EDGE clinical trials programme and C-Surfer and C-Salvage trials, which assessed grazoprevir / elbasvir (100mg / 50mg), with or without ribavirin, in patients with chronic hepatitis C infection.

Earlier, the firm received FDA breakthrough therapy designation for grazoprevir/elbasvir to treat patients infected with chronic HCV GT1 with end stage renal disease on haemodialysis, and for patients infected with chronic HCV GT4.

Source: Pharmaceutical-Technology.com (Kable, a trading division of Kable Intelligence Limited.)

More Mandates for FDA

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New proposals from Congress to spur innovation will strain resources needed for regulatory approval.

With a bipartisan “21st Century Cures” bill moving through Congress, and negotiations beginning on how the next round of user fees will shape FDA policies and priorities (see sidebar), there’s great optimism in Washington that these efforts will yield real improvements in biomedical discovery and drug development to speed new therapies to patients. FDA officials, though, are nervous about finding resources to implement new mandates while maintaining an efficient review process.

Despite broad support for the “Cures” bill negotiated by leaders of the House Energy & Commerce (E&C) Committee, there may be a long wait for Senate action. E&C chairman Fred Upton (R-Mich) is looking for final House approval this summer, but members of the Senate Health, Education, Labor and Pensions (HELP) Committee are crafting their own innovation legislation and don’t expect a bill until fall.

The House measure gained Democratic support by offering a hefty budget increase for the National Institutes of Health (NIH) and under pressure, agreed later to add a sizeable funding increase for FDA. The measure proposes to boost NIH funding by $5 billion over three years (to hit $35 billion in 2018) and provides another $10 billion over five years to support a new NIH Innovation Fund.

FDA is authorized less than $100 million a year to support clinical trial modernization and evidence development. More important, added language exempts FDA user fees from budget sequestration and proposes “pay for” options. But despite a groundswell in support for greater government funding for biomedical research, there’s no indication that Congressional appropriators will provide any new money for NIH or FDA.

Meanwhile, Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), fears that a law requiring new programs and multiple guidances will undermine her ability to meet review and approval commitments. This latest E&C proposal has “significant resource implications for FDA,” Woodcock stated at an April E&C health subcommittee hearing. CDER’s new drug review process is now “going at full speed, and we’d like to keep it that way,” she commented, warning that timely sponsor meetings important for accelerating innovative development programs “would be the first to go” if the agency gets further stretched on resources.

FDA’s first priority is to implement statutory requirements set by Congress, she explained. Next comes meeting user fee goals negotiated with industry. The extensive resources needed to advise on clinical programs and to collaborate on biomarkers might have to be scaled back.

Help on hiring

What FDA sorely needs, says Woodcock and others, is to cut some of the red tape and obstacles to recruiting and retaining experts able to address complex scientific and regulatory issues. Too-low salaries prompt experienced staffers to leave for more rewarding jobs in industry and academia, and complex government employment practices make it hard to attract top talent. Woodcock told the Senate HELP Committee that staff turnover “is a huge problem for us” and that FDA has “a desperate time” bringing in neurologists due to low salaries.

Jeffrey Shuren, director of the Center for Devices and Radiological Health (CDRH), similarly described FDA as the “training ground for industry,” as young professionals leave after a few years for industry jobs offering salaries two or three times what they make at FDA, and where the work load is more manageable. When medical reviewers depart right in the middle of processing an application, Shuren added, that ultimately hurts patients as well as regulated companies.

The “Cures” legislation would help FDA by raising some pay rates and making it slightly easier to employ certain specialists. Woodcock also would like new hires from biopharma companies to be able to place securities in blind trusts instead of having to sell them to come to FDA. And she sought more “direct hire authority” to speed up the employment process for certain health professionals able to “go toe-to-toe with industry scientists.”

Seeking agreement

To gain Democratic support for the Cures initiative, Republicans agreed to the NIH budget increase and dropped some controversial provisions, such as extended exclusivity on certain new medical products. But there is agreement to reauthorize the priority review voucher program for rare pediatric diseases, which is set to expire, as well as an initiative to spur development of new antibiotics, utilizing a modified approval pathway for therapies targeted to limited populations. The legislation encourages more sharing of research and clinical data by removing barriers to national interoperability of e-health records. And there’s support for telemedicine, for faster coverage decisions on new vaccines, and for a breakthrough program for medical devices.

Under the heading of achieving a “faster, safer and more personalized” research system, the “Cures” bill backs greater use of central, or “lead,” institutional review boards (IRBs) to oversee multi-site studies, authorizes greater use of “clinical experience” reports to help support FDA approval of certain new indications, and gives FDA flexibility to approve “qualified indications” based on clinical data summaries, as opposed to full case reports.

Payers as well as pharma companies support flexibility in presenting healthcare economic information to formulary committees and insurers, a change likely to increase industry investment in economic analysis, according to a report by Avalere Health. And a “medical education” provision would revise the “Sunshine” disclosure program to make it easier for marketers to distribute journal articles and medical textbooks to physicians and to support certain continuing medical education events.

Even though FDA already is doing much to accelerate biomarker qualification, the process could benefit from Congressional backing, says former FDA commissioner Andrew von Eschenbach. He emphasized at a recent Alliance for Health Reform briefing that biomarker assessment is key to furthering precision medicine and predicted that Congress will pass “transformational legislation” this year; just how big the bill will be, he added, is “a work in progress.”

By Jill Wechsler, PharmaExec.com

Cabazitaxel – carboplatin combination chemotherapy holds promise as treatment for advanced prostate cancer

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For more than a decade, oncologists using cytotoxic chemotherapy to treat patients with advanced metastatic castration-resistant prostate cancer (mCRPC) have relied on the sequential use of single agent taxanes such as docetaxel and cabazitaxel.

For example, docetaxel is commonly used as the “first-line” therapy, while cabazitaxel is used as the “second-line” therapy. A role for combination therapy using two or more chemotherapy agents at the same time has not been well studied.  However, results of a clinical trial presented at the American Society of Clinical Oncology meeting by researchers at The University of Texas MD Anderson Cancer Centre may change the perspective on a role for combination chemotherapy in advanced disease.

The study compared the effectiveness of cabazitaxel alone versus cabazitaxel combined with carboplatin – a type of platinum chemotherapy – in patients with mCRPC. To date, 160 men have been randomised to treatment with either the single or dual chemotherapy drug regimen. Each patient received up to 10 cycles of chemotherapy.

To monitor the effects of treatment, MD Anderson researchers tracked several variables including Progression Free Survival (PFS), as well as changes in blood levels of prostate-specific antigen (PSA) and bone-specific alkaline phosphatase (BAP, a marker of prostate cancer in bone cells). In addition, safety and toxicity were monitored for both patient groups.

Cabazitaxel – carboplatin combo demonstrated significantly longer Progression Free Survival versus single agent chemotherapy

Analysis and comparison of the data demonstrated that median PFS was significantly longer for patients receiving combination versus single agent chemotherapy (6.7 months vs 4.4 months, respectively). Furthermore, reductions in both PSA and BAP were greater for the combination therapy group. PSA reductions greater than 50% occurred 60% of the time with combined chemotherapy vs. 44% with the single drug. PSA reductions greater than 90% occurred 28% of the time with two chemotherapy drugs vs. 20% with one. In addition, BAP reductions greater than 50% for combination vs. single drug were 63% and 25% respectively.

Side effects, such as fatigue, anemia and neutropenia were comparable for both the single-drug regimen and two-drug regimen. In addition, there were no significant toxicity events.

“We believe cabazitaxel – carboplatin combination chemotherapy may become the clinical standard for advanced prostate cancer once additional safety, efficacy and overall survival data is generated,” explained Paul Corn, M.D., Ph.D., an associate professor of genitourinary medical oncology at MD Anderson. “Dr Ana Aparicio’s lab is currently developing tumour-specific biomarkers to identity patients with an aggressive variant of prostate cancer most likely to benefit from this approach.”

The study was funded by Sanofi.

By Victoria White, Europeanpharmaceuticalreview.com

Type 2 diabetes drugs linked to deadly ketoacidosis

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A new class of drugs, SGLT2 inhibitors, used to treat type 2 diabetes have been linked to diabetic ketoacidosis which can be deadly if left untreated.

A certain class of type 2 diabetes drugs can lead to a life-threatening condition called ketoacidosis, the U.S. Food and Drug Administration warns.

These prescription drugs are called sodium-glucose cotransporter-2 (SGLT2) inhibitors and include canagliflozin, dapagliflozin and empagliflozin. They work by prompting the kidneys to remove sugar in the blood through urine.

The drugs are sold under the brand names:Invokana (canagliflozin), Invokamet (canagliflozin and metformin), Farxiga (dapagliflozin), Xigduo XR (dapagliflozin and metformin extended-release), Jardiance (empagliflozin), Glyxambi (empagliflozin and linagliptin).

Between March 2013 and June 2014, the FDA received 20 reports of the drugs triggering ketoacidosis, in which levels of blood acids called ketones are too high. If untreated, ketoacidosis can lead to a diabetic coma or even death, according to the American Diabetes Association.

All 20 patients had to go to an emergency department or were hospitalised, the FDA said.

Ketoacidosis typically affects people with type 1 diabetes, but all of these cases involved people with type 2 diabetes and the condition manifested itself slightly differently than in people with type 1 diabetes, the FDA said in a news release.

The agency said it’s investigating the issue to see if changes are needed in the prescribing information for . The drugs are approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes.

Patients taking SGLT2 inhibitors should monitor themselves for any signs of ketoacidosis and seek immediate medical attention if they develop symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness, the FDA said.

Testing for ketones

Ketones can be detected with a simple urine test using a test strip, similar to a blood testing strip, and you should ask your health care provider about when and how to test for ketones, according to the diabetes association.

Patients shouldn’t stop or change their diabetes medications without first talking with their doctor. If ketoacidosis is confirmed in a patient, doctors should take the patient off SGLT2 inhibitor, take appropriate action to correct the condition and monitor sugar levels, the FDA advised.

Taken from Health24 / HealthDay

Synthetic Drugs: Evidence That They Can Cause Cancer

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Almost weekly, a new synthetic psychoactive drug comes onto the market somewhere in Europe that can be ordered legally and easily, for example as an incense blend, via the Internet.

Synthetic cannabinoids are difficult to identify chemically and the possible unwanted toxic effects that can occur following their consumption have so far barely been investigated. As part of the international EU project “SPICE II Plus”, which is now coming to an end, scientists from the MedUni Vienna’s Institute for Cancer Research have now also found evidence that synthetic substances damage the DNA of human cells and can therefore possibly have cancer-causing effects.

Synthetic cannabinoids, similar to tetrahydrocannabinol (the psychoactive ingredient of marijuana), bind to cannabinoid receptors in the human brain, triggering similar neurophysiological effects. These synthetic cannabinoids are marketed in incense mixtures as “legal highs” via the Internet and are “flooding the market”, as Siegfried Knasmüller from the Institute for Cancer Research at the MedUni Vienna warns.

“The substances are directly active, in other words they are not activated via enzymes that metabolise foreign substances”, explains Knasmüller. “The respiratory organs and the digestive tract especially are subjected to increased concentrations of these drugs. Our investigations on human cell lines in the laboratory have shown that synthetic cannabinoids, in the high concentrations found in cells in the oral cavity or in the lungs, for example, are likely to trigger damage to the DNA that may have significant consequences for the consumers of such substances. They damage chromosomes, and this is directly associated with cancer.”

Effects on consumers cannot be quantified

Synthetic cannabinoids bind very differently and some have an effect even in very small quantities. Consumers have absolutely no information about the varying levels of effect, since they are unaware of the detailed composition of synthetically manufactured drugs. Even with “known” products, the type and quantity of ingredients added change constantly. The risk of an unwanted overdose is correspondingly great. As a result, there have been repeated cases of damage to users’ health or poisoning, and in some cases users have even died.

Between 2005 and 2012, the European Union’s early warning system registered just under 240 new psychoactive substances that were disguised as incense blends, bath salts or plant fertiliser, and around 140 of them contained synthetic cannabinoids.

Source: Medical University of Vienna 

Sun Pharma and Technion form oncology research pact

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Mumbai-based Sun Pharmaceuticals Industries is teaming up with the Israel Institute of Technology Technion to develop new oncology drugs.

This agreement aims at the development of a joint project, based on new findings by Nobel Prize laureate Professor Aaron Ciechanover, Dr Gila Maor and Professor Ofer Binah – that can potentially lead to the development of novel anti-cancer drugs.

“We are very excited about this new endeavour between Sun Pharma, with the Technion. We are confident that this collaboration will help us move rapidly forward with our research” note Ciechanover and Binah. “We explored several collaboration alternatives, but Sun Pharma’s market leadership and its long term commitment have made this collaboration a very high priority for us.”

Whilst no financial details have been unveiled, the news leads to an unusual pairing between Sun Pharma as the world’s fifth largest speciality generic pharma company and India’s top drug firm – with the oldest university in Israel’s Technion, that was founded back in 1912.

Sun Pharma just recently closed its mega merger deal with fellow Indian giant Ranbaxy and began the integration of the two businesses. The firm says the combined force will now allow it to expand its R&D capabilities, increase its presence in emerging markets, and ‘strengthen its M&A bandwidth’.

Both Sun and Ranbaxy have provoked the ire of regulators over the past year with escalating manufacturing woes, as well as claims of insider dealing that almost brought the merger to an end. The deal was signed off by the US Federal Trade Commission in February.

This latest move sees the company aiming towards fruitful ties however, as its senior VP of business development Kirti Ganorkar notes: “This collaboration is part of the various initiatives that Sun Pharma is taking to enhance its specialty pipeline. Mutually beneficial partnerships with independent research institutes, especially world renowned institutes, such as the Technion, is our preferred route to bring to the market, innovative products for unmet medical needs.”

By Brett Wells, Pharmafile online

AZ and Takeda diabetes drugs get FDA safety update

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An FDA advisory committee has said that the labels of two type 2 diabetes drugs should be changed to warn of the risk of heart problems.

The panel discussed trial results suggesting that both AstraZeneca’s Onglyza (saxagliptin) and Takeda’s Nesina (alogliptin) – from the DPP-4 inhibitor class of diabetes treatments – could increase risk of hospitalisation due to heart failure.

Both drugs were found to have an increased risk of lower than 30% – the level defined as unacceptable by the trials – and were voted to have an acceptable safety profile. However, the panel recommended that the treatments’ labels should now include data from these trials to inform patients of the potential risk.

“Patients with diabetes are at an increased risk of cardiac related comorbidities such as heart disease and stroke, as well as hospitalised heart failure and cardiac death,” says Professor William White, on behalf of the steering committee and investigators for Nesina’s trial.

“Today’s advisory committee recommendation provides important information about Nesina that may be useful for prescribing physicians as they consider appropriate treatment options for patients with type 2 diabetes.”

The safety of diabetes drugs has been an area of increasing concern for the FDA, and in 2008 it requested pharma firms to conduct trials to assess the risk of cardiovascular problems in treatments such as these.

Results from Onglyza‘s SAVOR trial were analysed earlier this week, and suggested a 27% increase in hospitalisation due to heart failure in patients taking the drug. The committee voted 13 to one, with one abstention, that this was an acceptable risk.

There were also concerns that that the medicine may ‘significantly’ increase all-cause mortality, although analysis of the results from the FDA found no clear reason for the higher number of deaths compared to patients taking placebos.

In a statement AstraZeneca says it will conduct further investigations to better understand the hospitalisations arising out of the SAVOR results.

The FDA is not obliged to follow the advisory committee’s recommendations, but is likely to do so.

The US regulator is awaiting results from a similar study into Merck’s Januvia (sitagliptin) – another DPP-4 inhibitor – which are expected in June. These could show whether cardiovascular risks are a problem with the entire drug class or just individual treatments.

By George Underwood – Pharmafile online