2010: Pharma’s year in review

pharmafile | December 23, 2010 | Feature | Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing |  2010, Avandia, China, European healthcare spending, GSK, Obama, year in review 

2010 saw a harsh new economic reality dominate decisions in the US and Europe, but pharma seized on opportunities in emerging markets to maintain growth.

US reforms: Reforms to the US healthcare system were passed in March despite bitter opposition from the Republican party.

The new plan represents the biggest reform of the US healthcare system since the 1960s, and will extend health insurance coverage to 32 million more Americans.

A crucial component of Obama’s victory was the support of the US pharmaceutical industry. The leadership of US industry body PhRMA had decided to support the push for change, in contrast to a similar bill in the 1990s which it had vehemently opposed.

A spokesman for PhRMA said: “We believe comprehensive healthcare reform will benefit patients and the future of America.”

The passing of the bill was a highlight of an otherwise very uncomfortable year for President Obama, whose approval rating is suffering because of high unemployment and continuing economic problems in the US.

The healthcare bill proved to be a focus for the anger of Republicans, and especially the libertarian Tea Party movement, which said the bill embodied the spendthrift ‘big government’ approach which it opposes.

The November mid-term elections saw the Republican party seize control of the House, but fell short of gaining control of the Senate.

Republican John Boehner, the new leader of the House has vowed to repeal the bill, saying it would “kill jobs in America, ruin the best healthcare system in the world, and bankrupt our country”.

Repealing the law is, however, likely to be more or less impossible, and is not seen as a priority by most voters.

A public opinion poll by AP-GfK shortly after the mid-term elections found just 39% supported Republican plans to repeal the law, with 58% advocating further reform or retaining the bill.

Earlier in the year, PhRMA’s Ken Johnson reiterated its support for reform: “Done in a smart way, healthcare reform will benefit patients, the economy and the future of our nation.”

No one in America now doubts the need for reform. The US currently spends $2 trillion a year on its healthcare. This represents a very considerable 16% of the country’s GDP and is far higher than any other developed nation – most European countries spend around 10-12%. Worse still, US healthcare costs are expected to hit 20% of GDP by 2017.

For the pharma industry, the features it had most feared have been excluded from the final reforms, and the sector secured generous deals in pricing and a guarantee of a 12-year market exclusivity for biologics.

Despite all of the talk about emerging markets, the US is still the world’s most important and valuable market for the sector, thereby making the reforms equally momentus for the industry.

The pharma industry agreed in 2009 that it would contribute to cost reductions by guaranteeing savings of $80 billion over the next decade, in part by offering rebates and making brand name drugs more affordable to people over 65 years of age.

Healthcare and Europe: Healthcare represents one of the largest areas of governmental spend so cuts have been expected, but some have been far harsher than originally forecast. Despite the sluggish growth in the region’s pharma market in recent years, Europe is still important for the industry, accounting for more than 30% of the sector’s global revenues in 2009.

The dire economic situation in Greece led the country to slash its medicines prices by up to 27% in May, and since then a number of countries have followed with similar, if not as drastic, cuts.

Spain is to introduce a 7% cut in the price of branded medicines, and a 25% cut in the price of generics.

On 25 November the French Parliament adopted the law on Social Security financing (LFSS) that will trigger €2.4 billion of savings, including €860 million on pharmaceuticals and medical devices.

This cost-containment measure aims to attain the national expenditure target growth of 2.9% in 2011.

Germany represents the biggest pharma market in the EU but its coalition government, headed by Christian Democrat Angela Merkel, has made efforts over the past to break the ‘pharma monopoly’ that sees the country pay some of the highest drug prices on the continent.

In November, the lower house of its Parliament voted to control the cost of new prescription medicines by cutting prices by more than €2 billion ($2.76 billion).

Drug companies will now have a one-year window in which to negotiate prices with health insurers after introducing new drugs, but if no agreement is reached the Health Ministry would set a maximum price, and the drugs would undergo a cost/benefit analysis by Germany’s HTA body IQWiG.

Previously the pharma industry in the country could charge any price for their drugs, but the new legislation is set to end this privilege.

The new limits come on top of temporary rebates and price freezes on drugs that the government imposed last summer.

Italy is to cut €24 billion from its healthcare spending, €1.35 billion of which will come from reduced pharmaceutical spending. Italy will also cut cancer drug prices next year as it adopts a ‘pay for performance’ approach to drug pricing.

This will see the country cutting the price of several cancer drugs in 2011, after deciding that new studies showed them to be ‘less effective’ than the manufacturers claimed.

Pharma view

GSK’s chief executive Andrew Witty predicts that his company’s European revenues will shrink by at least 3% for the next year or two, and could worsen. During his Q2 results in July, Witty said: “We’ve seen some price pressure in the first half. It will accelerate as we move through the second half and actually I think it will be more of a 2011 phenomenon, in terms of how it ramps up.”

AVANDIA FUELS CALLS FOR GREATER DATA DISCLOSURE

In September GSK’s diabetes drug Avandia was  withdrawn from the market in Europe because of high levels of heart attack, heart failure and stroke in patients.

In the US, the FDA took a contrasting approach, by stopping short of a complete withdrawal of the product. The US authority’s decision permits cardiologists to use the drug in patients where it is considered the best option, despite the acknowledged raised risks.

A new analysis of all the available data by the UK’s regulator the MHRA concluded that Avandia’s benefits no longer outweighed its risks to patients, resulting in advice to withdraw the drug, which the EMA has now followed.

The decision to order its withdrawal was the culmination of a long period of doubt about Avandia’s side effects, concerns growing after a meta analysis was published in May 2007.

Many critics said regulators have been too slow to act, and were not vigilant enough in monitoring Avandia’s safety profile.

In particular, an investigation by BBC programme Panorama in early September this year revealed that the MHRA had made its recommendation to withdraw Avandia in June, but that the EMA had not yet acted on the advice.

It is not clear why the EMA delayed its decision.  The Agency commented that: “Emerging evidence points strongly to a modest increased risk for rosiglitazone [Avandia].”

The EMA pointed out that because diabetes itself raises the risk of heart attacks and strokes, it has been difficult to clearly establish whether Avandia had been “causative, contributory or coincidental in these cardiovascular disorders”.

Patients currently taking Avandia are advised to consult their doctor about alternative treatment, but should not stop treatment before seeing their doctor.

The EMA indicated that Takeda’s Actos (pioglitazone) a medicine in the same class, was not linked to the same levels of risk as Avandia.

GSK defends record

GlaxoSmithKline maintains that the drug should still be on the market in Europe. Speaking to Pharmafocus in October, GSK’s UK medical director Dr Pim Kon said meta-analyses may have shown a ‘signal’ of cardiovascular side effects four years ago, but she disputed the EMA’s interpretation of the data.

“We still believe Avandia is valuable to patients and has a positive benefit/risk ratio to type II diabetics,” she said.

Dr Kon was also clear GSK would not have acted any differently in retrospect, despite facing mounting criticism over its behaviour, including from the BBC’s Panorama programme and the British Medical Journal last month.

“We have acted responsibly and with integrity and I don’t see how we could have acted any differently,” she said.

The pivotal analysis of the data saw concerns grow after a meta was published in the New England Journal of Medicine in May 2007.

Conducted by independent cardiologist Dr Steve Nissen, this meta-analysis of GSK’s available data showed a link between Avandia and both heart attacks and an increased risk of fatal cardiovascular events.

But GSK maintains a discrepancy between Nissen’s data and GSK’s own RECORD trial data meant the meta-analysis was not a true representation of the data.

“GSK looked at the data as a whole – the discrepancy exists in the interpretation of the data because we have looked at it differently,” Dr Kon said.

She admitted that this was ‘confusing for the public’ as clinical data is difficult to interpret and many trials for Avandia trials have been undertaken with different endpoints.

A meta-analysis of 42 separate trials was submitted to the FDA in August 2006 and, when pushed on the matter, Dr Kon said this data showed there may have been “some signal of cardiovascular events”, but she added that in July 2007 an FDA committee said the drug had a positive benefit/risk ratio. Responding to the accusation that the company had tried to bury negative data from Avandia’s RECORD study (which began in 2001 and was published in 2009), Kon dismissed this saying GSK “acted responsibly”.

However, several emails between GSK executives in 2001 showed the company was willing to drop from the RECORD trials, two negative studies showing a link between use of Avandia and cardiovascular events, as they would put the drug in a ‘negative light’.

Asked whether GSK has an internal policy to stop the distortion or ‘cherry picking’ of data, Kon said: “GSK is fully committed to transparency, but we cannot say 100% that it couldn’t happen. We are going in the right direction and I believe completely that we are a highly ethical company.” Kon also noted that GSK publishes all of its clinical data for the public to see. However, this is something it was required to do after withholding important safety data on its antidepressant Seroxat back in 2008.

Pfizer data

In a separate development, researchers from Germany’s cost-effectiveness body IQWiG unearthed what was termed a ‘mountain’ of unpublished data from trials of Pfizer’s reboxetine that show that the antidepressant may be harmful.

They found published studies overestimated reboxetine’s benefit by 115% when compared to placebo and 23% when compared with other antidepressants, and that they also underestimated harm. Their findings were published in the British Medical Journal where they damningly concluded that: “Reboxetine is, overall, an ineffective and potentially harmful antidepressant.”

The researchers found that 74% of the data from patients in trials for the antidepressant had gone unpublished until this week.

Mandatory publication of pharma trials

The researchers used reboxetine as an example of a bigger problem within the industry. In their final remark in the BMJ, they said that all published evidence is affected by publication bias, “underlining the urgent need for mandatory publication of trial data”.

A ‘regulatory gap’ still exists in the EU whereby pharma companies are not legally required to make public all trial data. There is a centralised trial register in Europe, the EudraCT, but it is only available to be viewed by regulators and pharma, not the public.

MORE KEY PHARMA EVENTS FROM 2010:

February – ReNeuron, UBC ties up with PatientsLikeMe and generics companies’ vision

ReNeuron was been given the go-ahead to begin clinical trials of the first ever stem cell therapy for patients disabled by stroke.

The UK company gained final approval from the Gene Therapy Advisory Committee (GTAC) to conduct the a trial of its therapy ReN001, the first of its kind anywhere in the world.

Pre-clinical studies of ReN001 in rats have shown the therapy helped to reverse some stroke disability. Stroke is the third biggest killer in the UK after heart disease and cancer.

UCB broke new ground for a pharma company exploiting the internet and social networking to connect with patients.

The company launched an online community for US epilepsy patients to record ‘real-world’ experiences of the condition.

In addition to providing disease information the company hopes its partnership with PatientsLikeMe will also improve drug safety and ultimately lead to advances in epilepsy treatments.

UCB has ambitious plans for the partnership and has outlined a number of research projects in the pipeline, including one that takes aim at the spectre of adverse events – long the cause of pharma caution on any form of social networking.

The company will run a drug safety programme within the community that will capture adverse events associated with UCB epilepsy products and then report them to the FDA.

One month later it was joined on the community by Novartis, who began working with PatientsLikeMe on a section for people who have received organ transplants. Novartis’ transplant community will allow patients to monitor and share their progress and address common post-transplant issues, such as concerns about organ rejection or adherence to medication.

Novartis chief executive Joe Jimenez said: “We need to be closer to patients to understand their experience and their needs. An online experience allows patients to open up and share in a more personal and frank way.

“Our commitment to supporting this transplant community will shape the way we do our work, and ultimately help improve transplant patient outcomes now and in the future.”

Generic drug companies have set out their vision of a more ‘clear’ and ‘open’ market in Europe.

 Greg Perry, director general of the European Generic Medicines Association (EGA) is promoting the organisation’s ‘Vision 2015’ for easier access to market, just as the European Commission is looking into possible reforms.

Outgoing Competition Commissioner Neelie Kroes is pursuing investigations into the industry involving suspected illegal maneouvres by pharma companies to block the entry of generics.

March: NICE on Multaq

NICE gave preliminary approval of Sanofi-Aventis’ Multaq for the management of patients with atrial fibrillation.

The decision reversed an earlier initial ruling in December 2009, which said the drug was too expensive to recommend for NHS use.

NICE was persuaded that Multaq (dronedarone) is an advance over existing second-line anti-arrhythmic drugs such as amiodarone, sotalol and class 1c drugs.

In particular, the cost and clinical-effectiveness body said amiodarone and other anti-arrhythmic drugs (AADs) carried with them the risk of raised mortality in patients, something not seen in Multaq’s data. Sanofi-Aventis has deliberately held back the launch of the drug in the UK until the ruling was published, such is its importance to uptake in the health service.

April: Pfizer discloses US doctor payments

Pfizer disclosed in full its payments to US doctors to conduct clinical trials and to promote and educate their peers about its products.

The company was obliged to make the disclosures as part of a landmark US government case against the company for marketing violations, for which it was fined $2.3 billion in August 2009.

The data shows Pfizer paid $35 million to around 4,500 healthcare professionals over the six-month period of July-December 2009.

Approximately 1,500 experienced healthcare professionals were paid an average of $5,000 to provide “input and advice to ensure the company addresses the real needs of clinicians and patients”.

A further 2,800 healthcare professionals were paid an average of $3,400 to educate their peers about health conditions and promote Pfizer products.

Pfizer is the first company to disclose report payments made for conducting phase I – IV clinical trials in addition to releasing statements for speaking and consulting.

In 2009 Lilly published more general figures showing it paid an average of $1,000 to 3,400 healthcare professionals for ‘their services’ to Lilly in the first quarter of last year, and GlaxoSmithKline published its total spend on speaking and consulting fees paid to US healthcare professionals that totaled $14.6 million.

The new US health reform stipulates that all pharma companies must submit how much they pay doctors for their consultation as well as speaking arrangements, meals and all other perks.

May: Novo Nordisk’s Greek drama

Danish diabetes specialist Novo Nordisk threatened to withdraw its modern insulin products from Greece in protest at the country’s 25% price cut in drug prices.

Novo Nordisk’s chief executive Lars Rebien Sorenson said at the time that Greece’s actions would have a “rub-off effect on the European price level,” and argued that it also has an effect on other markets outside Europe where the Greek prices are used as a reference price in negotiations with governments.

Just one week after the war of words broke out between Novo and Greece, the Danish pharma firm decided to allow its insulin products back into Greece after the government agreed to a reduced 10% price cut.

Greece’s hospitals have built up substantial debts with both pharma and medical devices companies over the last few years.

A total of €1.2 billion was paid back to companies in December 2009, but a €5.6 billion in arrears will be paid off over the next few years through a government bond system.

These actions could produce a dangerous new precedent whereby pharma companies effectively hold countries to ransom by pulling their products if they believe the cost-containment measures are too harsh.

Andrew Witty, GlaxoSmithKline chief executive and president of EFPIA, was asked by Pharmafocus if it was right for pharma companies to copy Novo’s methods in Greece as a bargaining tool.

“If I can take my hat off as EFPIA president for a moment, I think it’s terribly poor that the industry displays actions and behaviours which aren’t empathetic to the challenges of our payers,” he said. “I think we’ve got to find ways of staying at that table and being constructive – walking away is not necessarily the right step.”

At the EFPIA meeting Witty noted that governments are the industry’s paymasters and, in the current economic climate, industry will need to find ways of working with them to strike a balance between drug development costs and access to medicines.

Working against each other will not “be helpful to the debate over pricing”, he added.

September: Pfizer slims down its pipeline

Pfizer reduced the number of drugs in its product pipeline as part of a broad refocusing of its R&D efforts.

Projects in phase I were set to bear the brunt of the cuts, accounting for 15 programmes out of a total of 31 that have either been halted completely or cut back as the company takes a hard look at which drugs will help it manage a number of looming patent expiries.

Pfizer said its updated pipeline would focus on ‘value and unmet medical need’ as it continues to integrate drugs developed by Wyeth, which Pfizer acquired last year.

The company’s new pipeline includes 26 programmes in phase III and nine programmes in registration, as well as 27 biologics and four vaccines across all phases of development, but phase I projects were reduced to 118.

October: China drives global pharma growth and GSK pleads guilty

The global pharma market is forecast to reach $880 billion by 2011, driven by growth in the Chinese market. Analysts at IMS Health predict pharma sales in China, now the world’s third largest market, will increase by over a quarter to more than $50 billion next year. Meanwhile, the 17 ‘pharmerging’ countries – IMS’ term for Brazil, Turkey, Russia, China, India, Mexico, South Korea, Venezuela, Poland, Argentina, Vietnam, South Africa, Thailand, Indonesia, Egypt, Pakistan, and the Ukraine – are forecast to grow at a more than respectable 15-17% during 2011, to end at $170-180 billion.

GlaxoSmithKline agreed to plead guilty to distributing adulterated drugs made at its now-closed facility in Cidra, Puerto Rico, and pay a $750 million fine.

The case brought by the US Department of Justice also saw details disclosed regarding a record whistleblower payment to Cheryl Eckard, a former quality assurance manager at GSK who will receive $96 million from the settlement.

According to the lawfirm representing Eckard, this is the first time that the US False Claims Act has been used to “hold drugmakers accountable for violations of government manufacturing standards”, and could set a precedent for other similar actions.

Eckard was dismissed in 2003 after raising concerns with the company’s management about manufacturing violations at the Cidra facility.

She notified the FDA of the situation and filed a lawsuit in 2004. GSK will pay $150 million to settle the criminal charges and $600 million for the civil claims, which relate to a number of cases of adulterated drugs manufactured at the Cidra plant between 2001 and 2005, according to a DoJ statement.

Brands cited in the case included anti-nausea medication Kytril (granisetron), the topical antibiotic Bactroban (mupirocin), Paxil CR (paroxetine) for depression and diabetes treatment Avandamet (rosiglitazone and metformin).

GSK failed to ensure that Kytril and Bactroban finished products were free of contamination from micro-organisms, it is alleged, while Paxil CR tablets made at the facility split and may not have had any therapeutic effect. In addition, Avandamet tablets may have had too little or too much active ingredient, says the DoJ.

Commenting on the case, US Attorney Carmen Ortiz, said: “As this investigation demonstrates, we will not tolerate corporate attempts to profit at the expense of the ill and needy in our society – or those who cut corners that result in potentially dangerous consequences to consumers.”

GSK senior vice president and head of global litigation, Perre Villareal, said the company “regrets that we operated the Cidra facility in a manner that was inconsistent with current Good Manufacturing Practice (cGMP) requirements.

“GSK worked hard to resolve fully the manufacturing issues at the Cidra facility prior to its closure in 2009 and we are committed to continuous improvement in our manufacturing processes,” he added.