Maxine Vaccine interviews two directors at Bona Pharma who are brightening the grey landscape of medical sales.

I’m soaking up the cosmetically enhanced atmosphere of Battersea’s Vauxhall Tavern when the leaders of Bona Pharma flounce subtly into view.

Managing Director Julian and Sales Director Sandy have brought style and verve to the strait-laced world of the pharma industry.

“We beat that Adele to the first name only thing,” Sandy assures me. “She copied our shoes as well.”

Reassuringly, they follow industry convention in one respect: they never get a round in. I order four happy hour cocktails (two for me, one each for them), and the Q&A begins.

Pf: “These are hard times for the pharmaceutical industry. The leading drug companies have all fallen over the patent cliff. How can they drag themselves up again?”

Julian: “Trolling reps everywhere, Sophie Hipgrave is your guide – follow her through the hazardous forest of fashion choices to the emerald city of fantabulosa.”

Sandy: “Most pharma is a work of performance art in the medium of naff. The industry needs to learn that pinstripe is not the only suit.” (Shudders.)

The duo have recently returned from an antipodean business trip. We debate the relative merits of their Bushwackers and my Brandy Alexander. Maybe some day we’ll design a head-to-head clinical trial.

Pf: “Is it fair to say that your marketing has ensured Bona Pharma has a strong rep in the outback?”

Julian: “Yes indeed. We miss him though.”

Pf: “Bona Pharma is known for its niche products. What success stories did 2012 bring you?”

Sandy: “We did well with our erectile dysfunction drug abonafil. But there was one customer who claimed it had worked a bit too well. The poor omi sued us for causing him to suffer from priapism. Though it had boosted his call rates no end.”

Julian: “Didn’t stand up in court.”

Pf: “Of course, the market is changing radically, even in the UK. How has Bona Pharma responded to the shift of healthcare into the community?”

Julian: “Well, I have a check-up once a week. He’s got an extended visa.”

Sandy: “Very extended at certain times. Never vada’d the like.”

Pf: “One question our readers will be keen to hear your answer to. How useful are recruitment companies to pharma?”

Sandy (sadly): “Elton John syndrome. Great voice, nante riah.”

Pf: “What one thing about pharma would you change?”

Julian: “Its name. Every farmer I’ve met has been into market penetration in quite the wrong way.”

Another round of happy hour cocktails – my expense account covers a multitude of gins – and then it’s time for the final question.

Pf: “In an era when Parliament is voting to legalise gay marriage, is there still any need for an underworld gay dialect designed to keep secrets and spread rumours?”

Sandy: “This is pharma, dear. Secrets and rumours are the world.”

Different statins vary in their potential to cause diabetes as a side-effect in certain patients, new research has shown.

Evidence presented at the World Congress on Prevention of Diabetes and its Complications (WCPD) in Madrid suggests that pitavastatin and pravastatin may pose less risk than other statins.

The Congress also noted that concern over diabetes risk has affected worldwide prescribing of statins in general.

Despite being the most-prescribed type of drug, statins – which have been shown to reduce blood cholesterol levels and this risk of cardiovascular events – have a range of medically significant side-effects.

Most notably, a meta-analysis of 13 trials with 91,000 participants has found that statin use is associated with 9% increase in risk of new-onset diabetes.

More recent studies suggest this effect varies strongly between drugs in the statin class, with atorvastatin increasing long-range blood glucose in intensive doses but with pitavastatin and pravastatin having no such impact.

The new J-PREDICT trial in Japan, due to conclude in 2015, is testing the effect of pitavastatin on risk of diabetes in 1,200 people with ‘pre-diabetes’ (impaired glucose tolerance).

Pitavastatin, the lead product of Japanese company Kowa, will be marketed (as Livazo) by Recordati in Europe, where it received MHRA approval in 2010.

Prof. Kausik Ray, Professor of Cardiovascular Disease Prevention at St George’s, University of London, said: “These insights demonstrate how the medical community is taking the diabetogenic risk of statins seriously and highlight the need for further research and guidance in how to treat patients with high cholesterol who are at risk of developing diabetes.”

Swiss biotech company Actelion has seen its share value dip following concerns over a late-stage drug trial in which 120 out of 740 participants died.

The results of the SERAPHIN phase III trial of macitentan, a drug candidate to treat pulmonary arterial hypertension (PAH), have still to be analysed.

A reported comment by Actelion’s CEO Jean-Paul Clozel that the trial results were “very unlikely” to show that the drug extended life triggered a 9% drop in the company’s share value.

Until the encrypted trial results are decoded and published in the second quarter of this year, Actelion said, the reason for the deaths will not be known and the trial cannot be declared a success or a failure.

According to company spokesman Roland Haefeli, “PAH is a deadly disease, therefore it is to be expected that people die. We did expect and observe deaths. Until the code is broken, we do not know [the cause].”

An analyst commented that there had been “a misinterpretation around CEO comments” and that “nothing negative was said”.

The SERAPHIN trial aimed to show that macitentan significantly reduced both morbidity and mortality in patients with symptomatic PAH, so patient deaths were anticipated as marking the point where the trial would end.

The trial is crucial for Actelion, which relies on macitentan to restore its profile in the PAH market following competition to its existing Tracleer drug by Gilead’s rival Letairis (ambrisentan).

Sales of Tracleer fell by 7% in 2011, and Actelion posted a net financial loss of 146m francs after a profit of 390m francs in 2010.

The company has also started a pivotal study of macitentan in patients with ischaemic digital ulcers.

Final NICE guidance on the use of Daxas (roflumilast), Merck Sharp and Dohme’s drug for maintenance treatment of severe chronic obstructive pulmonary disorder (COPD), recommends setting up a clinical trial to test its clinical and cost-effectiveness.

The Appraisal Committee confirmed draft guidance, which was not challenged, on the potential use of Daxas as an add-on to double or triple bronchodilator drug therapy for adults with severe COPD and a history of frequent exacerbations.

It is estimated that 88,000 people with COPD would be eligible for long-term treatment with Daxas in the suggested indication by 2015; however, the lack of relevant direct clinical trial evidence for the drug’s value in this context led the NICE Appraisal Committee to demand more robust data.

Daxas, an oral medication, is a long-acting enzyme inhibitor that targets cells and mediators important whose inflammation is believed to cause COPD.

NICE recommends use of the drug on an ‘only in research’ basis to generate relevant data about its benefits as an add-on to triple therapy (long-acting muscarinic antagonists plus long-acting beta2 agonists plus inhaled corticosteroids) or dual therapy (the first two of these).

Professor Carole Longson, NICE Health Technology Evaluation Centre Director, said: “There are a lot of people with COPD, and those likely to be treated with roflumilast could receive treatment for a long time. This meant that a high degree of uncertainty about the clinical and cost-effectiveness was not acceptable to the Committee.

“For this reason, the Committee has recommended a clinical trial of roflumilast in the same combination in which it would be used in clinical practice.”

GSK’s HerpeVac vaccine against herpes simplex is likely to be discontinued following a major phase III clinical trial that showed it to be ineffective in protecting women against either infection or genital symptoms.

In a trial of over 8,000 women, HerpeVac was found to be partly effective against the HSV-1 strain of the herpes virus but ineffective against the HSV-2 strain, which is more dangerous and clinically indistinguishable.

The trial results contrast with earlier findings that the vaccine showed strong efficacy against both strands of the virus in women whose regular partners had the disease.

“I think this is the end of the vaccine,” said study co-author Dr. Peter Leone of the University of North Carolina. “It would be difficult to imagine marketing a vaccine that would only work against HSV-1.”

The phase III study, sponsored by GSK and the National Institute of Allergy and Infectious Disease, enrolled 8,323 women aged 18–30 who were seronegative for herpes simplex antibodies. They were given three doses of HerpeVac, or a hepatitis vaccine as control, over six months.

The vaccine was found to be 35% effective against infection with HSV-1 and 58% effective in preventing genital symptoms from it, but wholly ineffective against HSV-2. Overall, this meant that it prevented infection in 22% of cases and prevented genital disease in 20%.

Two earlier studies had shown HerpeVac to be 73% and 74% effective in preventing genital disease from HSV-2 in seronegative women with seropositive long-term partners. It has been speculated that these women had already developed a certain level of immunity.

Dr Leone commented that the vaccine would probably have a limited public health benefit, and so will not be put on the market.

Michael Huggins, former North America President of bone implant specialist Synthes, has received a nine-month sentence for his role in an unauthorised clinical trial of bone cement that caused three human deaths.

Three other former Synthes executives, convicted of involvement in the same criminal activity, are awaiting sentence.

The US Justice Department had prosecuted the four executives in a drive to hold individuals to account for corporate crimes.

The executives had senior roles in Synthes’ Norian unit, which manufactured osteobiological implants. Norian was purchased by US company Kensey Nash earlier this year for $22 million.

Between 2002 and 2004, the Justice Department said, Norian carried out unauthorised clinical trials of Synthes’ Norian XR bone cement in surgeries to treat vertebral compression fractures (VCF), despite a warning against such use on the product label.

Initial studies had shown that the bone cement reacted chemically with human blood in vitro, producing clots – and that when used in a pig, the cement caused blood clots in the lungs.

Synthes continued to test the product on humans until it had caused three deaths, and even then the company misled the FDA, the Justice Department said.

In April 2011, Johnson & Johnson purchased Synthes for approximately $21.3 billion to merge it with its own troubled DePuy orthopaedic device business.

The FDA has approved Abbott’s next-generation Xience Prime drug eluting stent to treat patients with complex coronary artery disease.

The Xience Prime Everolimus Eluting Coronary Stent System is based on the company’s cobalt-chromium stent technology and is designed to enhance deliverability, flexibility, and more accurate stent placement in patients with symptomatic heart disease due to de novo native coronary artery lesions.

The approval was based on results from the SPIRIT PRIME clinical trial, a prospective, multi-centre, open-label trial involving 500 patients with coronary artery disease at more than 60 centres in the US and Australia. Clinical results show that the trial met its primary endpoint of low rates of target lesion failure (TLF) at one year.

Dr Marco Costa, principal investigator of the SPIRIT PRIME trial, said: “Drug-eluting stent technology continues to advance, leading to improved outcomes for patients with coronary artery disease.”

He said that the medical device “will improve our ability to access challenging, complex lesions, and thereby improve care for our patients”.

Robert Hance, Senior Vice President at Abbott Vascular, said that the FDA’s approval “expands the range of treatment options that we can offer physicians for the benefit of their patients with coronary artery disease”.

Xience Prime received CE Mark Approval in 2009.

Abbott recently split into two companies, one concentrating on research-based pharmaceuticals and the other (Abbott) on medical products.

The CHMP has recommended Astellas Pharma and Optimer Pharmaceuticals’ Dificlir (fidaxomicin) to treat adults with colon disease.

The drug specifically targets the bacteria causing the infection in the colon whilst avoiding ‘friendly’ bacteria in the gut of patients with the disease, which is also known as Clostridium difficile-associated diarrhoea (CDAD).

Ken Jones, President and CEO of Astellas Pharma Europe, said: “European patients with this potentially fatal disease can take encouragement from the positive CHMP opinion for Dificlir that a new medication for clostridium difficile infection may soon be available.”

Dificlir’s active substance is fidaxomicin, which belongs to the macrocyclic class of antibacterials and inhibits RNA synthesis by bacterial RNA polymerase.

Dr Xavier Luria, Head of Safety and Efficacy at the EMA, said: “This is a promising step forward in the Agency's drive for addressing patients' needs in infectious diseases.”

The positive opinion is based on Phase III clinical research data comparing fidaxomicin with oral vancomycin on patients in the US and Canada. Results of the studies showed that clinical cure was achieved at the end of ten days of treatment with both treatments. Furthermore, fidaxomicin had a significantly lower rate of recurrence of CDI compared to vancomycin.

Dificlir, known as Dificid in the US, was approved by the FDA in May for the treatment of CDAD in adults.

The European Commission will deliver its final decision within three months.

CDI is a serious illness resulting from infection of the internal lining of the colon by C. difficile bacteria. The bacteria produce toxins that cause inflammation of the colon, diarrhoea and, in some cases, death.

UK-based Astellas Pharma Europe manufactures and distributes pharmaceuticals globally with the intention to improve lives through the introduction of innovative and reliable pharmaceutical products.

Optimer Pharmaceuticals, is a biopharmaceutical company focused on developing and commercialising hospital specialty products to treat serious infections and address unmet medical needs.

Eli Lilly has received a positive opinion from the CHMP for Alimta as continuation maintenance therapy of advanced nonsquamous non-small cell lung cancer (NSCLC).

The recommendation is for the pemetrexed injection to be used as part of maintenance therapy, a relatively new concept in lung cancer treatment to commence immediately after patients have completed first-line treatment, in an effort to sustain disease control.

Dr Allen Melemed, Senior Medical Director of Alimta at Lilly Oncology, said: “Lung cancer is one of the most difficult cancers to treat and new therapy options are much needed.”

The CHMP’s recommendation will be reviewed by the European Commission, which will decide whether to approve the treatment for indication in Europe.

Dr Melemed commented: “If approved, Alimta would be the first tailored treatment option based on efficacy that can potentially extend lives beginning in first-line treatment and continuing through maintenance in advanced nonsquamous non-small cell lung cancer.”

No chemotherapy is currently approved as ‘continuation maintenance’ treatment. Currently approved lung cancer maintenance therapies use different medicines in the first-line and maintenance phases of treatment.

The CHMP's opinion was based on clinical research results from Paramount, a randomised, double-blind Phase III study involving patients with advanced nonsquamous NSCLC. Participants received initial therapy with four cycles of Alimta plus cisplatin. Patients whose disease did not progress continued to the maintenance phase, where survival was assessed in patients who received Alimta plus best supportive care (BSC), compared with those who received a placebo plus BSC.

Alimta is already approved in the first-line, maintenance and second-line settings in the EU and US for the indication. The treatment was originally recommended by NICE in September 2009 to treat the cancer on the NHS in the UK, but reversed its decision in December 2009, citing data uncertainties. NICE came to a final recommendation in June 2010.

Lung cancer is the most common form of cancer in the world, causing 1.3 million cancer deaths each year. NSCLC contributes to 85-90% of all lung cancers.

The first antibiotic inhaler device has been launched in the UK to treat chronic lung infections in adults and older children with cystic fibrosis (CF).

The TOBI Podhaler (pictured) from Novartis is a hand-held inhaler that delivers a new dry powder form of tobramycin to fight chronic Pseudomonas aeruginosa (Pa) lung infections, a common cause of death in people with CF.

The new device is estimated to save almost half an hour treatment time per day in people with CF over the age of 6, increasing their independence and quality of life.

CF affects 9,000 people in the UK. A life-threatening condition, it makes the lungs vulnerable to chronic infections.

Clinical studies have shown that treatment with tobramycin inhalation powder reduces treatment time by 72% compared with the nebulised drug.

Professor Stuart Elborn, Professor of Respiratory Medicine at Queen’s University, Belfast, commented: “People with CF have to endure a lengthy regimen of treatments and physiotherapy every day, so the time saved using tobramycin inhalation powder is significant.”

The new tobramycin inhalation powder has been produced using Novartis’ patented PulmoSphere technology. In trials, it was successfully inhaled in 5–6 minutes, whereas the nebuliser solution takes 20 minutes. For a twice-daily regimen, this saves approximately 28 minutes per day.

The dry powder inhaler is also less vulnerable to bacterial growth than the nebuliser, and needs no battery.

“We are proud to be launching TOBI Podhaler: a product that clearly demonstrates how we are applying innovative technology to better meet the needs of people with CF, helping them to lead independent and active lives,” said Dr Tim Cave, Medical Director of Novartis Pharmaceuticals UK.

Based in Basel, Switzerland, Novartis supplies a diversified portfolio of healthcare products including pharmaceuticals, diagnostics and drug delivery devices.