Pharmaceutical Industry

PHARMAC CONSULTS ON ITS DECISION NOT TO FUND SOLIRIS

PHARMAC is seeking feedback on its proposal to decline a funding application for eculizumab, also known as Soliris. (1) As noted in the February issue of the AWHC newsletter, Soliris which is manufactured by Alexion Pharmaceuticals, is the world’s most expensive drug – the cost of treating one PNH patient for a year is over $600,000.

PNH (paroxysmal nocturnal haemo-globinuria) is an extremely rare blood and immune system disorder. It is an acquired disease characterised by the destruction of red blood cells, blood clots, impaired bone marrow function and a risk of developing leukaemia. The median survival after diagnosis is 10 years; however some patients can survive for decades with only minor symptoms. There is currently no known cure for PNH.

Current treatment in New Zealand for PNH aims to relieve symptoms rather than cure the condition, and includes blood transfusion to treat anaemia, immune suppression with steroids to suppress ongoing red blood cell destruction and anticoalgulation with warfarin to prevent or treat blood clots. (1)

Soliris/eculizumab is given via an intravenous infusion administered to patients fortnightly in a hospital setting. It is not a cure but it relieves the symptoms associated with PNH and it needs to be used for the rest of the patient’s life.

PHARMAC received an application from Alexion Pharmaceuticals to fund Soliris in November 2011. Clinical advisors considered the application at the Pharmacology and Therapeutics Advisory Committee (PTAC) in February 2012, at the Haemotolgy Subcommittee  in August 2012, and at February and March 2013 PTAC meetings. The minutes of these meetings are available on PHARMAC’s website.

PHARMAC’s consultation document explains that the reason it is proposing to decline funding is because the price requested by the drug company is extreme.  

The New Zealand patient group that was established a year ago, and Dr Humphrey Pullon, a consultant haematologist in Hamilton, appeared on Morning Report on 22 May arguing that PHARMAC had overestimated the numbers of patients (12–20 patients instead of 8–10 patients) who would be considered for treatment with this drug and that the price that Alexion Pharmaceuticals had offered the drug to PHARMAC was the lowest in the world. (2)

Alexion Pharmaceuticals has funded both the Australian and New Zealand campaigns for drug. An email sent to Dr Humphrey Pullon several months ago asking about his ties to the drug company has not been replied to.   

References
1. http://www.pharmac.health.nz/news/item/proposal-to-decline-a-funding-application-for-eculizumab
2. http://www.radionz.co.nz/national/programmes/morningreport/audio/2555923/pharmac-under-fire-by-patients,-doctor,-over-drug-decision.asx

May 2013



“GIVE US THE $600,000 MIRACLE DRUG”

At the end of January 2013 the front page of the NZ Herald featured a by now familiar story of a small group of patients that were desperately lobbying for a very expensive drug. (1) In this case it was the world’s most expensive drug – costing $500,000 a year per patient. (2)

The drug in this story is eculizumab, otherwise known as Soliris, and it is used to treat patients with PNH (paroxysmal nocturnal haemoglobinuria) which is an extremely rare blood and immune system disorder. The Herald article stated that in New Zealand “up to 20 people are thought to have PNH” with eight of them considered candidates for Soliris.

PNH
PNH is an acquired rather than genetic disease characterised by the destruction of red blood cells, blood clots, impaired bone marrow function, and a 3-5% risk of developing leukaemia. The red blood cells become prone to destruction by parts of the person’s own immune system due to the lack of a special protein which normally protects the red blood cells from being destroyed by the immune system. It is closely related to aplastic anaemia, and up to 30% of newly diagnosed cases of PNH evolve from aplastic anaemia. The median survival after diagnosis is 10 years; however some patients can survive for decades with only minor symptoms. (3)  

The drug company
Soliris is manufactured by Alexion Pharmaceuticals which has given its new drug to three of the eight New Zealand patients with PNH under a compassionate access scheme. It is not clear why the drug company has chosen to fund only three of the eight.

Towards the end of the NZ Herald article it was revealed that there was a New Zealand support group for patients with PNH and they had begun this lobbying campaign which was being funded by Alexion. A follow-up editorial in the Herald on Sunday reported that the support group had been given an “unrestricted educational grant” from Alexion and the campaign was being orchestrated by Viva, a Sydney PR firm that represents Alexion Pharmaceuticals. (4)

The editorial referred to the fact that “Alexion is a NASDAQ-listed firm that last year projected a net revenue of $1.35 billion from sales of Soliris around the world.” (4) $1.35 billion from just one drug! It’s enough to make the Ministry of Health’s eyes water. Alexion Pharmaceuticals' website states that "the Company is also developing a portfolio of four innovative drug candidates beyond eculizumab for the treatment of additional severe and ultra-rare disorders."

The editorial continued: Alexion is “not just a world leader in the medical laboratory; it’s a world leader in arm-twisting governments to fund its extortionately-priced drug.” The pressure is being applied by slick campaigns that appear to be run by patient groups, but are in fact being run by Alexion’s PR firms in Australia and Canada.

The New Zealand patient group which was established less than a year ago has a very professional website that features a video of Dr Humphrey Pullon, a consultant haematologist in Hamilton, alerting us to “the developing public scandal that is seriously ill PNH patients being denied access to a life-saving treatment.” (5) His promotion of Soliris is even accompanied by a soundtrack. There is also an online “PNH petition for life” for us all to sign or download.

According to the Herald on Sunday, “these campaigns are effective: 24,000 Australians signed a petition supporting the nation’s 70 PNH sufferers, forcing the federal government to begin funding the drug in 2011. The Canadian government also capitulated – though that nation’s provinces banded together to knock down Alexion’s prices. They were aided in their hardball negotiations by the discovery that Alexion was supplying Soliris to the US at half the price it was quoting to the rest of the world.” (4)

A visit to the Wikipedia website on Soliris in the course of researching this article revealed that the site had recently been updated to include the fact that New Zealand is the only country in the OECD that does not fund Soliris. Its reference is the TV3 news item on 24 January that repeated what was in the NZ Herald article that morning. This “important” fact also features on the NZ PNH support group’s website.

A link on another PNH support group’s website to an article on long-term treatment with Soliris published in 2011 in Blood, the weekly publication of the American Society of Hematology, showed that all the researchers had financial ties to Alexion Pharmaceuticals. (6)

Another dangerous drug
The drug.com website states that “Soliris affects your immune system, and using this medication may increase your risk of serious infection such as meningitis. You must be vaccinated against meningococcal infection at least 2 weeks before you start treatment with Soliris. If you have been vaccinated in the past, you may need a booster dose.” (7)

Alexion Pharmaceuticals’ own website states that the US product label for Soliris includes a boxed warning advising that “life-threatening and fatal meningococcal infections have occured in patients treated with Soliris. Meningococcal infection may become rapidly life-threatening or fatal if not recognised and treated early.” (8)

Of course this fact isn’t included on the New Zealand patient group website. Nor is the fact that there are no vaccines for some strains of meningococcal infections, and that some like the MeNZB vaccine only last for a couple of years, if that. What is on the website is the claim that “Our only hope for survival rests in the hands of PHARMAC.”

Actually, it doesn’t. It rests in the hands of Alexion Pharmaceuticals which can certainly afford to lower the price of its obscenely over-priced drug. The PNH Support Association of NZ should be lobbying Alexion Pharmaceuticals, not NZ taxpayers.

References
1. http://www.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=10861091
2. http://www.forbes.com/2010/02/19/expensive-drugs-cost-business-healthcare-rare-diseases.html
3.http://www.hopkinsmedicine.org/kimmel_cancer_center/types_cancer/paroxysmal_nocturnal_hemoglobinuria_PNH.html
4. http://www.nzherald.co.nz/health/news/article.cfm?c_id=204&objectid=10861630
5. http://www.pnhsanz.org.nz/index.html
6. Richard Kelly et al. “Long-term treatment with eculizumab in paroxysmal nocturnal hemoglobinuria: sustained efficacy and improved survival.” Blood. 23 June 2011 Volume 117, Number 25.
7. http://www.drugs.com/soliris.html
8. http://www.alxn.com/SolirisAndPNH/AboutPNH/AboutPNH.aspx


For the latest on the battle for the truth about Tamiflu go to - 

http://www.newsweek.com/2014/11/21/medical-science-has-data-problem-284066.html


THE BATTLE FOR THE TRUTH ABOUT TAMIFLU
In an unprecedented move the British Medical Journal (BMJ) has begun an online open data campaign in an effort to achieve independent scrutiny of data from clinical trials. The major target of its first initiative is Roche, the pharmaceutical company that manufactures the antiviral drug oseltamivir, more commonly known as Tamiflu. On its website the BMJ states that “working with others, we seek to highlight problems caused by lack of access to data, and we welcome any suggestions on how to take things further.” (1)

Around 2008/2009 New Zealand was one of many countries around the world that began spending millions of dollars on stockpiling Tamiflu which Roche claimed was the drug of choice for the treatment and prevention of influenza A and B viruses. When the H1N1 (swine flu) pandemic began in mid 2009, demand for Tamiflu skyrocketed.

How effective is Tamiflu?
The US Department of Health and Human Services said it would save lives and reduce hospital admissions. The European Medicines Agency said it would reduce complications. The Australian and New Zealand health agencies agreed. (2) But where is the evidence to support these claims?

This is where the Cochrane Collaboration comes into the picture. The Cochrane Collaboration is a vast independent non-profit international collaboration of academics that produces hundreds of systematic reviews on medicines every year. Given the enormous sums of money that were now being spent on Tamiflu, the UK and Australian governments asked the Cochrane Respiratory Diseases Group to update its earlier reviews on Tamiflu.

The previous review published in 2008 had found some evidence that Tamiflu did indeed reduce the rate of complications associated with the flu virus. However, an online comment posted by a Japanese paediatrician called Keiji Hayashi alerted Tom Jefferson, the head of the Cochrane Respiratory Group that he had made a mistake. According to Ben Goldacre, the author of “Bad Pharma,” this comment triggered “a revolution in our understanding of how evidence-based medicine should work.” (2)

Basically what Keiji Hayashi pointed out was that Tom Jefferson’s positive findings were based on data from one paper, an industry-funded meta-analysis which summarised the findings of 10 earlier trials of which only two have ever been published in the scientific literature. The two trials that were published were funded by Roche, authored by Roche employees and Roche-paid “external” experts. The results of eight key trials of Tamiflu were never fully published, and a brief summary concluded that there was insufficient data to show it reduced complications. This means the data is not reliable enough.

Realising that Keiji Hayashi was quite right, Tom Jefferson contacted Roche and asked for the missing data. This was the beginning of what has so far been a three-year battle and which led to the BMJ’s open data campaign.

In an open letter to Roche about the Tamiflu trial data, BMJ editor, Fiona Godlee wrote “The Cochrane reviewers now know that there are at least 123 trials of oseltamivir [Tamiflu]  and that most (60%) of the patient data from Roche’s phase 3 completed treatment trials remain unpublished. We have concerns on a number of fronts: the likely overstating of effectiveness and the apparent under-reporting of potentially serious adverse effects.” (3)

After three frustrating years of trying to get access to the data, Tom Jefferson and his colleagues have given the BMJ their entire email correspondence with Roche, and shared their correspondence with the World Health Organisation (WHO) and the US Centers for Disease Control and Prevention. (1)

WHO’s independence questioned
Questions were raised in 2010 about the role of WHO and the secrecy surrounding the identities of the 16 emergency committee members formed to advise it on the H1N1 pandemic. Articles published in the BMJ in June 2010 raised concerns about whether the pharmaceutical industry had insiders on the WHO emergency committee. (4)

In February 2012 Tom Jefferson emailed WHO, asking WHO scientists how its review process had led to it including Tamiflu in its March 2011 “essential medicines” list.  Had it asked the manufacturers of neuraminidase inhibitors such as Tamiflu and Relenza for the unpublished trial data? And what had they made of Cochrane’s conclusion “that there is no evidence that oseltamivir can limit the spread of influenza.”

WHO told Tom Jefferson that it had commissioned several evidence reviews, including one on Tamiflu that would shortly appear in a peer reviewed medical journal. It promised to alert him when the review appeared. (5)  

Tom Jefferson was even less impressed with the response he received from the Center for Disease Control. Even the US Food and Drug Administration described Tamiflu’s effects as modest.

“Despite this, WHO and CDC have been extensively promoting the drug. WHO has made Tamiflu one of the essential drugs, so it sits next door to aspirin, penicillin, cortisone,” he said. 

Ben Goldacre says in his new book, “Drug companies around the world have produced some of the most amazing innovations of the past fifty years, saving lives on an epic scale. But that does not allow them to hide data, mislead doctors, and harm patients.” (2)

In New Zealand we have Medsafe. But the only information on Tamiflu on Medsafe’s website is produced by Roche which claims that Tamiflu can prevent you from catching the flu. (6) There is actually no evidence that Tamiflu is any better than an aspirin.

References
1. http://www.bmj.com/tamiflu
2. Ben Goldacre. “Bad Pharma.” Fourth Estate. 2012.
3. http://www.bmj.com/tamiflu/roche/rr/611576#alternate
4. http://www.womenshealthcouncil.org.nz/Features/Hot+Topics/Swine+Flu+-+H1N1.html
5. David Payne. “Tamiflu: the battle for secret drug data.” British Medical Journal. 2012;345:e7303
6. http://www.medsafe.govt.nz/consumers/cmi/t/tamiflusus6.pdf



THE MYTH OF RESEARCH & DEVELOPMENT COSTS
Numerous books, a growing torrent of papers in medical journals as well as occasional media reports have all attempted to alert governments, health departments and the general public to the growing health crisis caused by the way in which the pharmaceutical industry operates.

In August and September 2012 the British Medical Journal (BMJ) featured two articles that revealed how drug companies put profits before the development of new drugs, choosing instead to tinker with existing drugs and produce minor variations that offer few advantages but result in a steady stream of profits. In the process they have also produced an epidemic of serious adverse reactions that have added to national healthcare costs. (1) (2)

In a paper entitled “Pharmaceutical research and development: what do we get for all that money?” published on 7 August 2012, Professors Donald Light and Joel Lexchin reveal how the drug companies exaggerate research and development costs in order to lobby for more protection from free market competition. An independent analysis found that only 1.3% of revenues are devoted to discovering new molecules compared with an estimated 25% spent on promoting their drugs, giving a ratio of basic research to marketing of 1:19. 

While the pharmaceutical industry continues to churn out numerous articles claiming that the costs of research and development are unsustainable for the small number of new drugs that are approved, figures show that the reported costs rose by $34.2 billion between 1995 and 2010, but revenues increased six times faster – by $200.4 billion. The authors of the paper reveal how the hidden business model for pharmaceutical research, sales and profits depends on turning out scores of minor variations on existing drugs, some of which become market blockbusters.     

Canada’s experience
An analysis of Canada’s pharmaceutical expenditure found that 80% of the increase in its drug budget is spent on new, patented medicines that did not offer substantial improvements on less expensive alternatives available before 1990. (3) The major contributors to the increase in costs are the newer hypertension, gastrointestinal, and cholesterol drugs, including atorvastatin, the fifth statin on the Canadian market. 

Along with this, independent reviews have concluded that about 85-90% of all new drugs over the past 50 years have provided few benefits and considerable harms. One study found that 29% of the new biological drugs approved by the European Medicines Agency (EMA) received safety warnings within the first 10 years on the market, and therapeutically similar drugs by definition have no advantages to offset their unknown risk of increased harm. (4)

Another paper by Corinna Sorenson and colleagues appeared in the BMJ in September 2012. “Evidence of comparative efficacy should have a formal role in European drug approvals” argued that drug manufacturers should have to show how their new drugs compare to existing medicines before the EMA approves them. (2)

The lack of early comparative efficacy evidence can result in the widespread use of potentially less efficacious and unsafe drugs. An example of this is the diabetes drug rosiglitazone. The relative effectiveness of rosiglitazone as compared to the existing drug treatment for diabetes emerged only after years of widespread use, with rosiglitazone being shown to increase the risk of heart attacks and cardiovascular death. (2)

By requiring the drug companies to prove that their new drug offers a therapeutic advantage over older, less costly medicines before they are approved, the authors claim that clinicians, patients and other healthcare decision-makers will be able to determine whether a new drug is superior, equivalent, or inferior to the existing alternatives.

It will also reduce the toll of morbidity and mortality in patients who currently are being used as guinea pigs in what are in essence unofficial and unacknowledged drug trials.

References
1. http://www.bmj.com/content/345/bmj.e4348.pdf%2Bhtml
2. http://www.bmj.com/content/343/bmj.d4849.pdf%2Bhtml
3. SG Morgan et al. “”Breakthrough” drugs and growth in expenditure on prescription drugs in Canada.” British Medical Journal 2005;331:815-6.
4. TJ Giezen et al. “Safety-related regulatory actions for biologicals approved in the United States and the European Union.” Journal of American Medical Association 2008;300:1887-96.