Dutch medical trial using Viagra stopped after 11 babies die

A Dutch trial with the drug best known under the brand name Viagra, has been immediately halted after 11 babies of mothers using the medication died, one of the participating hospitals said on Tuesday.

When the trial was stopped on Monday, roughly half of 183 pregnant women participating were taking sildenafil, the Amsterdam University's Academic Medical Centre (AMC) said.

A similar Canadian study has been halted because of the Dutch findings, although the researchers say there have been no negative side effects reported in that study. 

A professor at the University of British Columbia confirmed 21 Canadians have been taking part in the trial. They were recruited in 2017 under Health Canada approval, with funding from the Canadian Institutes of Health Research.

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The Canadian trial's principal investigator, Dr. Ken Lim, said all three recruiting sites in Canada have been suspended.

"We are not aware of an increase in adverse outcomes," among the Canadian participants," Lim said in a statement.

"We contacted the one Canadian woman who was currently in the trial, directing her to stop taking the drug or placebo."

The Dutch study started in 2015 and involved 11 hospitals. It was designed to look at possible beneficial effects of increased blood flow to the placenta in mothers whose unborn babies were severely underdeveloped.

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Around 15 women who took the medication have not yet given birth.

"Previous studies have shown that sildenafil would have a positive effect on the growth of babies. The first results of the current study showed that there may be adverse effects for the baby after birth," the AMC said.

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Yet the results showed that 17 babies were born with lung conditions and 11 died. Among the roughly equal control group, just three babies had lung problems and none died.

Among the women taking sildenafil, 11 of the babies died due to "a possibly related lung condition" that caused high blood pressure in the lungs and may have resulted from reduced oxygen levels.

'We cannot take chances'

An interim analysis found that the chance of blood vessel disease in the lungs "appears to be greater and the chance of death after birth seems to have increased. The researchers found no positive effect for the children on other outcomes," the AMC said.

Stephen Evans, a professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said the small number of trials with pregnant women has limited our knowledge of medicines in pregnant women.

"There have been other studies in this area, both involving preliminary work using animals and using pregnant women, and there was no indication that the treatment was dangerous based on previous research," he said.

UBC's Lim said although there were no known negative reactions in Canada, "we cannot take any chances with the health of mothers and their infants," and researchers will look into previous studies on sildenafil.

"We are working co-operatively with our international research partners in the Netherlands, the United Kingdom, Australia and New Zealand to better understand the cause of the results in the Netherlands, and how they relate to results being reported by U.K. and other researchers, which did not indicate any evidence of harm," Lim stated.

Sildenafil was originally developed by Pfizer but is now off patent and available as a generic. Pfizer had no immediate comment.

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Boys should be given HPV jab, says vaccine committee. Here’s what happens next.

It’s nearly a decade since the human papillomavirus (HPV) vaccine was first introduced in the UK to help protect against the virus that causes most cases of cervical cancer. But until now, it has only been routinely offered to girls.Today, the Joint Committee for Vaccination and Immunisation (JCVI) recommended that adolescent boys should now also receive the vaccine.When and how this will happen is now down to the Government. But the recommendation comes from years of mounting evidence around likely health benefits and overall cost effectiveness.

HPV and cancer

HPV is a big family of viruses. There are more than 100 different types and some are more dangerous than others. While some low-risk types cause growths like warts or verrucas, there are thirteen high-risk types that are linked to cancer.HPV is very common, with 8 in 10 people infected at some point in their life. Usually our bodies clear the infection without it causing any problems. But in some cases a lasting infection can lead to cancer.This is because the virus damages the infected cells’ DNA and causes them to start dividing out of control, setting them on the road to cancer.Thanks to the vaccination programme, many people know that HPV causes cervical cancer – in fact it’s linked to all cases of the disease in the UK. But HPV is linked to other cancers too – including anal, penis and some types of mouth and throat cancer.

Why wasn’t the HPV vaccine always available for boys?

The HPV vaccine protects against 4 types of HPV. Two are linked to cancer: HPV 16 and 18, which together cause around 7 in 10 cervical cancer cases in the UK. The vaccine also protects against HPV 6 and 11, which cause most genital warts.The vaccine has been available to girls in the UK since 2008. It was initially only recommended for girls as the strongest evidence of health benefits and cost effectiveness was for cervical cancer and genital warts.Since the vaccine was introduced, we’re starting to see HPV infections in people who have been vaccinated falling. This suggests the vaccine is preventing HPV infection and, in the future, this should prevent cervical cancers.But HPV is linked to cancers in men as well as women.Men who have sex with women will get some protection from the current vaccination programme if their partner is vaccinated. The same can’t be said for adult men who have sex with men .In 2015, the JCVI, which advises UK health departments on vaccines, recommended extending vaccination to adult men who have sex with men. This group of men are at a higher risk of anal cancer. Up to the age of 45, these men can request HPV vaccination at sexual health clinics.But up until today, the programme hadn’t been recommended for boys, as the JCVI weren’t convinced it would be cost-effective.Today’s decision brings the UK in line with other countries including the US and Australia, which already offer the vaccination to boys.

Who will be offered the vaccine?

The JCVI has recommended the vaccine for boys aged 11-13, similar to the vaccination programme for girls. HPV vaccination is most effective in people who haven’t ever had an HPV infection. And as HPV is mostly transmitted through close sexual contact, vaccination is offered at a young age when people are unlikely to have had any sexual experiences.Men above the vaccination age who don’t have sex with men won’t be offered the vaccine. But it’s important to remember that most people clear HPV infections without them causing any symptoms or problems. And for most cancers linked to HPV there are also other ways to reduce your risk through things like not smoking or drinking less alcohol.

What happens now?

The recommendation for a gender neutral vaccination programme for adolescents has been years in the making. The next step is for the Government to formally accept the recommendation and extend the programme to boys.Until it does, we won’t know the details of when and how the programme will be rolled out. Once they have accepted the recommendation, the Government must publish a plan and timetable for the roll-out.This will need to be accompanied by more details on the programme itself. When the vaccine was first offered to girls in the UK, a ‘catch-up’ programme was introduced for girls up to the age of 18, and we want the Government to do the same for boys.Finally, the programme will do nothing if people aren’t aware it’s happening. We want to see a national awareness campaign to clearly communicate about the vaccine and its potential benefits, as well as new information for parents and boys.By offering the vaccine to everyone aged 11-13, the number of cases of HPV, along with the cancers they cause, could be dramatically reduced in the future.

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FDA Approves Krintafel (tafenoquine) for the Radical Cure of Plasmodium vivax Malaria

 GSK and Medicines for Malaria Venture (MMV) today announced that the United States Food and Drug Administration (FDA) has approved, under Priority Review, single-dose Krintafel (tafenoquine) for the radical cure (prevention of relapse) of Plasmodium vivax (P. vivax) malaria in patients aged 16 years and older who are receiving appropriate antimalarial therapy for acute P. vivax infection.Dr. Hal Barron, Chief Scientific Officer and President of Research and Development, GSK, said: “Today’s approval of Krintafel, the first new treatment for Plasmodium vivax malaria in over 60 years, is a significant milestone for people living with this type of relapsing malaria. Together with our partner, Medicines for Malaria Venture, we believe Krintafel will be an important medicine for patients with malaria and contribute to the ongoing effort to eradicate this disease.”

Dr. David Reddy, Chief Executive Officer of MMV said: “The US FDA’s approval of Krintafel is a major milestone and a significant contribution towards global efforts to eradicate malaria. The world has waited decades for a new medicine to counter P. vivax malaria relapse. Today, we can say the wait is over. Moreover, as the first ever single-dose for this indication, Krintafel will help improve patient compliance. We are proud to have worked side-by-side with GSK for more than a decade to reach this point. Our focus is now on working to ensure the medicine reaches the vulnerable patients that need it most.”

The approval was based on efficacy and safety data from a comprehensive global clinical development P. vivax radical cure programme designed in agreement with the FDA. Thirteen studies in healthy volunteers and patients directly supported the programme. The primary evidence for the clinical efficacy and safety of the 300mg single-dose, to which more than 800 subjects were exposed, was provided by three randomised, double-blind studies: DETECTIVE Part 1 and Part 2 (TAF112582) and GATHER (TAF116564). The results of the two phase III studies were announced in June 2017. The submission included data analysed from a total of thirty-three studies involving more than 4,000 trial subjects exposed to the 300mg single-dose and other doses of tafenoquine.With the approval of Krintafel, the FDA awarded GSK a tropical disease priority review voucher. The tropical disease priority review voucher programme is designed to encourage development of new drugs and biological products for prevention and treatment of certain neglected tropical diseases affecting millions of people throughout the world.The new drug application (NDA) was submitted by GSK to the FDA in November 2017 and a regulatory submission was also made to the Australian Therapeutics Good Administration (TGA) in December 2017. A decision from the TGA is awaited. Approvals by FDA and TGA will be informative to other regulatory agencies for their own approval process in malaria-endemic countries where tafenoquine will be provided as a not-for-profit medicine to maximise access to those who need it most.

About Krintafel (tafenoquine)

Krintafel is an 8-aminoquinoline derivative with activity against all stages of the P. vivax lifecycle, including hypnozoites. It was first synthesised by scientists at the Walter Reed Army Institute of Research in 1978. GSK’s legacy in the research and development of tafenoquine as a potential medicine for malaria commenced over 20 years ago. In 2008, GSK entered into a collaboration with the not-for-profit drug research partnership, MMV, to develop tafenoquine as an anti-relapse medicine for patients infected with P. vivax. The tafenoquine clinical programme is part of GSK’s global health programme aimed at improving healthcare for vulnerable populations.

Important Safety Information

CONTRAINDICATIONS

Krintafel should not be administered to:

• patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency or have not been tested for G6PD deficiency
• patients who are breastfeeding a child known to have G6PD deficiency or one that has not been tested for G6PD deficiency
• patients who are allergic to tafenoquine or any of the ingredients in Krintafel or who have had an allergic reaction to similar medicines containing 8-aminoquinolines.

WARNINGS AND PRECAUTIONS

Hemolytic Anemia Breakdown of red blood cells (hemolytic anemia) may occur in a patient who has G6PD deficiency. G6PD testing must be performed before prescribing Krintafel. Treatment with Krintafel is contraindicated in patients with G6PD deficiency or unknown G6PD.

G6PD Deficiency in Pregnancy or Lactation The use of Krintafel during pregnancy may cause hemolytic anemia in a G6PD-deficient fetus. Krintafel is not recommended during pregnancy. Females of reproductive potential should avoid pregnancy or use effective contraception for 3 months after the dose of Krintafel.

A G6PD-deficient infant may be at risk for hemolytic anemia from exposure to Krintafel through breast milk. Infant G6PD status should be checked before breastfeeding begins. Krintafel is contraindicated in breastfeeding women when the infant is found to be G6PD deficient or the G6PD status of the infant is unknown. A woman with a G6PD-deficient infant or if the G6PD status of the infant is not known should not breastfeed for 3 months after the dose of Krintafel.

Methemoglobinemia Asymptomatic elevations in methemoglobin have been observed in the clinical trials of Krintafel. Physicians should carefully monitor individuals with nicotinamide adenine dinucleotide (NADH)-dependent methemoglobin reductase deficiency and advise patients to seek medical attention if signs of methemoglobinemia occur.

Psychiatric Effects Serious psychiatric adverse reactions have been observed in patients with a previous history of psychiatric conditions at doses higher than the approved dose. The benefit of treatment with Krintafel must be weighed against the potential risk for psychiatric adverse reactions in patients with a history of psychiatric illness. Due to the long half-life of Krintafel (15 days), any signs or symptoms of psychiatric adverse reactions that may occur could be delayed in onset and/or duration.

Hypersensitivity Reactions Serious hypersensitivity reactions (e.g., angioedema) have been observed with administration of Krintafel. Due to the long half-life of Krintafel (15 days), any signs or symptoms of hypersensitivity adverse reactions that may occur could be delayed in onset and/or duration. Physicians should advise patients to seek medical attention if signs of hypersensitivity occur.

ADVERSE REACTIONS

The most common adverse reactions (≥5%) observed for Krintafel in clinical trials were dizziness, nausea, vomiting, headache, and decreased hemoglobin.

DRUG INTERACTIONS

Physicians should avoid coadministration of Krintafel with drugs that are substrates of organic cation transporter-2 (OCT2) or multidrug and toxin extrusion (MATE) transporters (for example, dofetilide, metformin).

To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

GSK - a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com

Medicines for Malaria Venture (MMV) - MMV is a leading product development partnership (PDP) in the field of antimalarial drug research and development. Its mission is to reduce the burden of malaria in disease-endemic countries by discovering, developing and facilitating delivery of new, effective and affordable antimalarial drugs.

Since its foundation in 1999, MMV and partners have built the largest portfolio of antimalarial R&D and access projects ever assembled, and brought forward seven new medicines that are already saving lives. MMV's success is based on its extensive partnership network of around 160 active pharmaceutical, academic and endemic-country partners in more than 55 countries.

MMV's vision is a world in which innovative medicines will cure and protect the vulnerable and under-served populations at risk of malaria, and help to ultimately eradicate this terrible disease.

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2017.

Source: GSK

Posted: July 2018

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