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Oncology directions

With increasingly expensive cancer drugs, what price should be paid for innovation?
Oncology directions

Summer in Chicago for the pharma industry this year meant one thing: showcasing the best it has to offer in the most competitive and arguably most pressing therapy area - oncology.

The huge American Society of Clinical Oncology conference is typically abuzz with companies chomping at the bit to show off their latest innovations and hoping for a bounce in share prices for treatments that have aced a late-stage clinical trial.

In 2015, the buzz was very much around cancer immunotherapies and came just after approvals for the first in a new class of programmed-cell death-1 (PD-1) and programmed cell-death ligands-1 (PD-L1s) treatments from Merck & Co and Bristol-Myers Squibb. These new medicines teach the body to find and destroy cancerous cells - a system usually turned off when a patient has cancer - and have the ability to treat a multitude of oncologic disorders, including melanoma and lung cancer. Roche and AstraZeneca are also looking to break into this PD-1 and PD-L1 market, which is expected to be worth around $30bn by 2020.

BMS is currently seen to be the leader in the race to take the greatest share of this market, and published data at ASCO for its PD-1 drug Opdivo (nivolumab) that showed it could help patients live longer who have the most common type of lung cancer, and who had already been treated. BMS' Fouad Namouni told reporters at the event: “This marks the end of the chemotherapy era in second-line treatment of lung cancer.” The firm also posted some similarly encouraging data for the drug in advanced liver cancer.

Meanwhile, BMS' main rival for PD-1 drug market share Merck & Co showed off some impressive data for its drug Keytruda (pembrolizumab). This treatment has a licence for melanoma in the US and is also seeking a lung cancer indication, but at ASCO it was looking to branch out further, and posted positive data on head and neck cancer. Among evaluable patients in the early-stage study the overall response rate to Keytruda was 24.8% - a clinically significant improvement over the 19.6% ORR reported at last year's ASCO by the firm.

Many cancer patients are facing severe financial strain, even bankruptcy in some cases

What price innovation?
These data are all positive news for a therapy area that admittedly gains a lot of attention from the industry, but where real breakthroughs are often limited. 
The main talk of ASCO this year, however, was not focused on new innovations, but on the often eye-watering price tags being asked of payers.

Opdivo, as an example, costs $150,000 a year in the US, or around $12,500 per month. It is also the seventh drug approved by the FDA in melanoma since 2011 - coming after a near thirty-year absence of any new treatments for a cancer that is seeing a rapid rise in cases. Opdivo was approved in melanoma on data that showed 32% of participants on the drug had their tumours shrink (known as an 'objective response rate' or ORR). This effect lasted for more than six months in around one-third of the participants who experienced tumour shrinkage. More recent phase III data also demonstrated superior overall survival (OS) in advanced melanoma - the golden standard in oncology trials - demonstrating a one-year survival rate of 73% for Opdivo, versus just 42% for the chemotherapy agent dacarbazine. This is certainly impressive - but doctors at the event argued that new medicines should be producing these types of response and survival rates over a medicine that was first approved in the 1970s.

There is also concern that oncology drugs are typically being priced at a premium because of the fear of the disease, and the hype generated by events such as ASCO. BMS is set to do well out of the drug: Opdivo has analysts estimating a fairly wide range of peak sales figures, but typically the average is that it will be bringing in revenue of around $6bn by 2020, making it one of the biggest-selling drugs in the world. And these price tags and blockbuster predictions are similar across the entire range of new oncology drugs, with Keytruda having the same price tag as its rival.

We aim to signal the drugs with a large magnitude of clinical benefit which should be endorsed across Europe

Drug scoring system
A group of medical experts from the European Society for Medical Oncology (ESMO) - the European version of ASCO - have been assessing the value of new medicines, and have set up a unique scoring system to look beyond pricing, and find what value each medicine has for the patient. The group presented its scoring system at the ASCO meeting and includes scores for more than 70 cancer drugs and has been published in the Annals of Oncology journal.

Prof Richard Sullivan from Kings College London, an ESMO group member, said they wanted pharma companies and those who fund drug discovery to focus on inventing meaningful drugs that help patients, rather than just making profits. He said: “Over the past decade, more and more medicines have been going on to the market with lower and lower levels of benefit.”

In reality, few medicines are being brought forward as being curative, with the majority being used in palliative or end-of-life care. A licence does not need to show that it can cure the disease or even have a major clinical effect - as long as it shows some efficacy and has a tolerable risk-benefit profile, a cancer drug will typically gain a licence. But the ESMO experts argue that this is being translated into prices that simply aren't related to a medicine's value.

The ESMO magnitude of clinical benefit scale scores drugs according to the results of the clinical trials they have been through, from one - providing the least benefit to patients - to five. Drugs that score between one and three are not doing well, Sullivan said. He explained: “Where they don't score above three, you have to ask: are they really delivering clinical benefit?”

Most of the drugs in lung cancer score four, but Roche's lung cancer drug Tarceva (erlotinib) scored just one. Out of 14 drugs for bowel cancer, three score four - but the rest all score less. For advanced breast cancer, Novartis's newly acquired breast cancer drug Tyverb (lapatinib) scores five, but there are four drugs that score three or less, including Eisai's breast cancer medicine Halaven (eribulin). In melanoma, eight out of nine drugs score four, showing a mixed picture across the entire therapy area.

Sullivan and his colleagues hope the drug regulatory bodies will use this scoring system as a way to think about their decisions to approve the low benefit drugs - although regulators are not currently expected to take cost into consideration when approving or rejecting a licence for a medicine. ESMO said it also wanted the best drugs to get an approval rating that means they will be high priority for use in all countries.

Rolf Stahel, the president of ESMO, said: “As the international organisation committed to the interest of the oncology community at large, we are concerned about some anti-cancer medicines approved by the European medicines agency not being available or affordable to patients when prescribed.

“We aim to signal the drugs with a large magnitude of clinical benefit which should be endorsed across Europe for rapid patient access, especially when these medicines are recommended through evidence-based standards set forth in the internationally recognised ESMO clinical practice guidelines.”

Cancer and bankruptcy 
At the same meeting another system was introduced - this time to directly assess drug prices. Known as the 'value framework', this system calculates a score - called the 'net health benefit' - and is based on clinical trial data.

Drugs for advanced cancer are given a score from 0 to 130. Up to 80 of the points are based on a drug's effectiveness in prolonging lives, delaying the worsening of cancer or shrinking tumours. Then up to 20 points can be added or subtracted based on side effects. And up to 30 bonus points can be granted if the drug relieves cancer symptoms or allows a patient to go without treatment for a period of time. The costs of the drug are listed separately, rather than incorporated into the final score for a drug.

This is a different system - and one step shorter - from what a number of health technology assessors already do, such as England's NICE, which uses a complicated quality-adjusted life years formula (QALY) to assess value. It also decides whether a drug should be funded by the state-run NHS, whereas the US has an insurance-based system - although state help is available via Medicare and Medicaid for the elderly and the poor.

Dr Richard Schilsky, chief medical officer of the oncology society that helped create this value framework, said the price of new cancer drugs now averaged about $10,000 a month in the US - with some reaching $30,000 a month. “Many cancer patients are facing severe financial strain, even bankruptcy in some cases,” he said.

As an example, Roche's multi-licensed oncology drug Avastin (bevacizumab), when added to chemotherapy, had a net health benefit of 16 out of 130 possible points using the system, when used as an initial treatment for advanced lung cancer. Its monthly cost was $11,907, compared to $182 for the chemotherapy alone. And it was even worse for Lilly as its chemotherapy agent Alimta (pemetrexed) for the same use as Avastin, had a net heath benefit of zero, with a cost exceeding $9,000 a month. This was compared to about $800 a month for the drugs it was compared to in the clinical trial.

The framework of assessing medicines is currently just a proposed methodology that is open for public comment, and not a new set of rules governing how doctor's and payers should value medicines.

Before, the information [on drug value] wasn't there. It allows the patient and the doctor to at least talk through the issues

Rising prices
In the US, both the industry and many politicians in the Senate and Congress have long opposed any cost restrictions on cancer drugs.

When new health rules now known as 'Obamacare' were being debated by the country's lawmakers, before eventually becoming law in 2010, those opposing the rules (who were predominately from the Republican Party) named any attempt to create a US health technology assessment (HTA) body as 'death panels'. The notion of an American HTA system was quickly dropped.

But, as prices for new oncology biologics have risen above inflation nearly every year for two decades, doctors - and now even patients - are starting to question just why these new treatments are so expensive.

Dr Lee Newcomer, senior VP for oncology at US health insurer UnitedHealthcare - and a member of the task force that developed the framework - explained: “Before, the information [on drug value] wasn't there. It allows the patient and the doctor to at least talk through the issues.”

UnitedHealthcare is mounting a similar effort of its own, Dr Newcomer said as it now requires oncologists to get prior approval from the insurance company for every cancer drug they administer. The company will then track what happens to patients and eventually provide information to doctors about how well each drug works.
Randy Burkholder, VP for policy and research at the US drug lobby group the Pharmaceutical Research and Manufacturers of America (PhrMA), said in a statement to PME that drugs represented only 20% of cancer treatment costs.

He added that the larger clinical trials that the oncology society used to make its value calculations “might not be as relevant” as treatment becomes increasingly personalised, based on genetic analysis of a patient's tumour.

Value
Both of the new methodologies are just ideas and not set to be implemented; but what is striking is that they were being put forward at the world's largest cancer conference where innovation and science have always taken the centre stage.

The US is a laissez-faire market and has always fought off attempts at governmental control over pricing on nearly all products, but especially on healthcare and medicines - this may also help explain why it has some of the most expensive cancer drugs in the world, with many nearly double the price paid for in Europe.

Certainly drugs are expensive to make - around $1.5bn per medicine on average - but payers are now simply unable to afford prices which are rising above inflation year-on-year. So the industry will need to start communicating value far better in the coming years, or face stricter barriers to market access - even in countries like the US. 

Article by
Ben Adams

is PMGroup editor

21st August 2015

From: Research

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