Many new drugs offer more hype than hope
RISING PROFITABILITY OF CANCER MEDICINE MAY BE WHY PROGRESS ON TREATMENTS CAN SEEM PAINFULLY SLOW
The issue: Many new cancer drugs are prohibitively expensive but offer patients more hype than hope. Possible solutions: Regulators should require more patient benefit before approving cancer drugs, and tie their prices to how much they improve treatment.
For a group of desperately ill Canadians, the news release seemed to offer genuine hope.
A drug just approved by Health Canada, it said, provided “an important new option” — a form of personalized medicine for the mostly younger, non-smoking patients stricken by a surprising sub-type of lung cancer.
Only one element was missing from the 2015 release: any suggestion that Zykadia would actually make those people tangibly better.
While an early stage study found the medicine shrunk tumours in about half of patients, there is no evidence — a footnote to the announcement conceded — it helps them live longer or improves their quality of life.
Still, manufacturer Novartis charged a small fortune for the drug: about $122,000 a year.
It is just one among an unprecedented wave of specialized cancer medications that have arrived in recent years, often heralded as potential turning points in the long slog to defeat the disease — with costs to match.
WE’VE REALLY SQUANDERED A LOT OF RESOURCES.
While some of the new cancer drugs have transformed lives, others seem to offer more hype than hope. All come at a steep price that is challenging government drug plans, workplace insurers and patients.
A National Post analysis of the 17 cancer drugs, including Zykadia, to come on the market in 2015 and 2016, reveals that only three had evidence of improved “overall survival” — that is, they extended lives — when approved by Health Canada.
Trial results since approval show survival benefits for four others — from 1.4 to six months on average — but for over half, it remains a question mark whether they will give very sick patients any more time than existing treatments.
Their list prices range from $4,700 to $33,000 a month.
“It is becoming increasingly difficult to disregard the costs of these new therapies — side-effect costs, costs to quality of life and financial costs … especially when the benefits are very, very small,” said Dr. Chris Booth, an oncology professor and researcher at Queen’s University in Kingston, Ontario. “The vast majority … are associated with extremely modest advances.”
The Pan-Canadian Oncology Drug Review, a government-funded body that gauges the cost-effectiveness of treatments, recommended against provinces covering six of those 17 medications.
Decisions are pending on four drugs; for the others, a positive rating was conditional on the list price being lowered.
The new drugs’ mixed reviews are, in a way, a microcosm of the massively funded war on cancer itself, an illustration of why the disease still ranks as Canada’s biggest killer after 50 years and hundreds of billions of dollars in worldwide research.
The rising profitability of cancer medicine may actually be at the heart of why progress can seem painfully slow — and we need a new war on cancer.
One prominent American oncologist suggests the high prices the drugs command are an incentive for companies to play it safe, invent new “me-too” medications that mimic other, successful products and move the needle forward only marginally.
The result has been, in effect, misuse of large chunks of the massive investment devoted to cancer research: billions of dollars spent developing treatments the world could do without, as riskier projects with the potential to pay far higher dividends go wanting, argues Dr. Tito Fojo.
“I just look back over the last 15 years and (feel) we’ve really squandered a lot of resources pursuing meaningless targets,” said Fojo, a Columbia University oncology professor.
Such concerns have led to calls for regulators like Health Canada and the U.S. Food and Drug Administration to raise the bar — require more substantial benefits before approving a cancer drug — and for value-based pricing. That means linking the cost of a drug to its scientifically proven value.
The industry and some patient groups, however, caution against such a hardnosed approach to medications that they say can benefit certain sub-sets of patients, even when the overall clinical-trial results may not look impressive.
“Lack of evidence doesn’t mean there’s lack of benefit, and sometimes with a patient you don’t know until you’ve tried,” said Deb Maskens, a kidney cancer patient and founder of the advocacy group CanCertainty. “There is nothing so powerful as seeing a patient who should be dead, who’s had a complete remission.”
Indeed, people with cancer are surviving longer; the proportion of Canadians still alive five years after being diagnosed has edged up to 63 per cent from 56 per cent between the early 1990s and late 2000s. The Canadian Cancer Society credits the improvement partly to better treatments, but also to more screening that allows cancers to be spotted earlier.
In fact, cancer used to be something of an afterthought for the pharmaceutical industry, whose profits stemmed largely from drugs treating chronic conditions like hypertension and high cholesterol — pills taken by millions of people for years at a time.
The turning point, said Fojo, came with the arrival in the early 1990s of Taxol, which worked against several advanced cancers. It quickly became a top seller and, as one of the most expensive drugs on the market, twigged industry to the disease’s profit potential.
The R&D that followed has been bearing fruit. There have been some major success stories: Herceptin for treating an aggressive form of breast cancer; Gleevac for adult leukemia; the socalled BRAF-inhibitors for melanoma; and the muchheralded immunotherapy drugs showing promise with a variety of cancers.
“Some of these drugs are changing lives,” said Dr. Maureen Trudeau, head of medical oncology at Toronto’s Sunnybrook Health Sciences Centre. She cites Opdivo, a new melanoma treatment, which keeps 30 per cent more patients alive after a year than previous therapy. “It’s incredible.”
Yet the list of drugs Health Canada has approved in 2015 and 2016 suggests that, despite high pricetags and hyped press releases, many fall well short of being wonder cures.
The gold-standard for testing medicines is the double-blind clinical trial, where a new drug is compared with a placebo or existing treatment. But 13 of the recent cancer medicines were approved based on early phase trials, at least seven with no comparison group at all, and what are called “surrogate endpoints.”
Surrogate endpoints are ways of measuring, in theory, a drug’s benefit before determining if it actually makes lives longer or of better quality. Those surrogates include progressionfree survival (PFS), which actually says nothing about how long patients live, but means the tumour or blood cancer does not advance over a given period of time.
Similar to PFS is response rate, the percentage of patients whose tumour was shrunk by the drug.
Health Canada, in line with U.S. and European regulators, says it accepts such relatively preliminary results because they are, in fact, a harbinger of extended life — and actual survival improvements are hard to measure in short trials.
Plus, the pressure is on to get promising new cancer treatments to market quickly, and gauging whether they actually prolong people’s lives can take too much time.
There is a fundamental flaw with the approach, Booth and other experts argue: Except in rare instances, neither progression-free survival nor response rate accurately predicts whether a drug will stave off patient deaths, said the Queen’s professor.
Trial data released after approval of the recent 17 cancer drugs did show survival gains for some. A study found the BRAF-inhibitor medicine Cotellic extended median overall survival by six months for advanced melanoma patients compared with a placebo — considered a triumph in oncology.
For patients, improvements of even a couple of months can mean seeing a child graduate, or simply living to fight another day, said Louise Binder of the Canadian Cancer Survivor Network.
“We shouldn’t pooh-pooh drugs that may not be home runs but do keep us in the game,” she said. “It may keep me alive long enough for something really amazing to come along. Am I entitled to that? Am I not entitled to that? Is it false hope? I don’t think so.”
But news certainly has not been rosy for all the 17 drugs since they won government approval.
Opdivo, at $8,200 a month, is considered a major breakthrough for melanoma. But a trial released back in August found it was no more effective than existing chemotherapy for lung-cancer patients, causing manufacturer Bristol-Myers’ stock to plunge.
Blincyto, costing a massive $33,000 every 28 days, was found to extend median survival for some late-stage adult leukemia patients by 3.7 months. But an alert from Health Canada last July — six months after it was approved — warned there is mounting evidence it can also trigger potentially fatal inflammation of the pancreas.
A trial suggested Zydelig improved overall survival slightly for advanced leukemia sufferers, but additional studies over a year ago found a high rate of death and other serious side-effects in early stage patients, leading to another Health Canada warning and one analyst to say the drug was “dead in the water.” It costs a relatively economical $4,700 a month.
Indeed, most of the drugs come with a long list of toxic side-effects. Companies argue it’s wrong, however, to dismiss drugs simply because of toxicity or the seemingly incremental progress some represent, and say the hefty prices reflect not just their benefits, but massive investment.
Novartis cites evidence that developing a single medicine costs as much as $2.6 billion.
Elaine Campbell, until recently a spokeswoman for Innovative Medicines Canada, the brand-name drug trade association, said a narrowly focused cancer drug can be brought to market for “a few hundred million.” But the task is not easy, as regulators require they be tested and approved on terminal patients who have few other options.
“It’s so, so hard to show overall survival of patients who have failed multiple courses of therapy along the route and are literally weeks or days away from death,” said Campbell. Such drugs “have made it to market in the face of an almost daunting lack of survival.”
Still, some of the pricing policies are difficult to fathom.
Novartis, for instance, charges $7,000 a month for its drug Afinitor, whether the dose is the recommended 10 milligrams, 5 mg or 2.5 mg.
“It is reprehensible in my mind,” said Trudeau, the Sunnybrook oncologist.
Whatever the reason for their hefty prices, the new wave of cancer drugs is putting stress on public and private health plan funders, with much more to come. There’s an estimated 1,800 cancer drugs in the development pipeline.
And a growing percentage — expected to reach 60 per cent by 2020 — are oral pills or injectables that patients take at home. That means that in many provinces, those sick people must pick up the cost themselves somehow, while treatment offered in hospitals is always covered under medicare.
The provinces have joined together to try to negotiate down the price of cancer drugs they cover.
But the workplace drug plans that millions of Canadians depend on must pay the list price, and face increasing pressure from the costs, said Michael Biskey, president of Express Scripts Canada, which manages some of those plans.
Maskens said many plans have placed lifetime or annual caps on the drug costs they’ll reimburse.
Yet the fact many payers — especially in the U.S. — are still willing to pay those prices encourages companies to just follow the lead of rivals, said Fojo. Next week: Part 3: The Future