East Bay Times

When it comes to cancer drugs, greed can be good

The FDA just approved Keytruda as a “first-line,” go-to treatment for certain patients with lung cancer.  Doctors can now treat patients with Keytruda right off the bat, rather than first prescribing traditional chemotherapy. Merck share prices soared in expectation of a big return on the drug maker’s investment.

Yet this happy news for patients and investors comes on the heels of the clinical trial failure of another promising drug. In late-stage clinical trials, Opdivo — which is already approved for a subset of cancer patients — failed to demonstrate better results than chemotherapy for the patient population under study.

The FDA didn’t approve the medicine for wider use, a decision that wiped out $20 billion in market value for its manufacturer, Bristol-Myers Squibb.

The disparate fates of Keytruda and Opdivo illustrate the risks and rewards of biopharmaceutical research. Both Bristol-Myers Squibb and Merck invested staggering time and resources into developing their drugs. Both have demonstrated considerable benefits in cancer care. Both ventured into first line use. But only one bet ultimately paid off.

Without powerful incentives, no company would take on the multibillion-dollar challenge of drug development. Medical innovation depends on profitability. If Americans want cutting-edge drugs, they need a thriving pharmaceutical industry.

Developing a new drug and acquiring FDA approval is a painstakingly slow process. This year alone, Merck spent $2 billion on Keytruda-related research.  But it paid off — Merck has now developed a drug that successfully slows the progression of advanced lung cancer and reduces death rates by 50 percent among a subset of patients.

Opdivo has also achieved incredible results for a subset of patients. Bristol-Myers Squibb hoped it would work for a broader range of patients, and undertook extensive clinical trials to test that hypothesis. That gamble ultimately didn’t pay off. But that sort of risk-taking is exactly the behavior that drives medical innovation forward.

New medicines like Keytruda and Opdivo are able to target the genetic mutations specific to a particular class of tumors without wreaking havoc on the rest of the body.  Older therapies — like chemo or radiation — work on a large number of patients, but they also are painfully imprecise, destroying normal healthy cells alongside tumors.

Unfortunately, the very precision of the new therapies means that they aren’t the right option for all patients. We need to encourage more research and more clinical trials on a broad array of patients, to find which therapies work best for the many varieties of the monstrous, $122 billion per year killer we call “cancer.”

In recent decades, new therapies have delivered big gains in the fight against cancer. Medical innovation has multiplied the number of cancer survivors from 3 million in the 1970s to 14 million today.  For lung cancer patients, five-year survival rates have increased by over half, and 83 percent of that progress is thanks to new drugs.

But extending life is only part of the goal; improving quality of life also is important. The latest cancer drugs are much less toxic than chemotherapy.  They don’t come with debilitating side effects like fatigue, nausea, increased risk of infection, gastrointestinal problems, and hair loss.  Patients can take them orally in the comfort of their homes rather than traveling to clinics.

Such medical progress isn’t guaranteed. Politicians have campaigned hard for greater regulation of drug prices. Those measures, such as a ballot initiative in California to cap drug prices and another in Colorado to establish a single-payer health system, failed this election season. But the voices urging crackdowns on drug company “greed” won’t go away anytime soon.

Supporters of such regulation no doubt sincerely want to help patients. But to paraphrase Wall Street’s fictional Gordon Gekko, “greed” is good for patients. Because the risks of drug development are so huge, drug companies need a chance to recoup their investments in spades. Without the possibility of big rewards, investors simply won’t fund lifesaving and life-improving research.

For every Keytruda, there are many more promising medicines that disappoint in clinical trials and don’t gain the FDA’s stamp of approval. Discovering and delivering more breakthrough drugs to patients depends on the right incentive structures.

Sandip Shah is the founder and president of Market Access Solutions (MKTXS). He spent nearly three decades working at large pharmaceutical firms, where he developed pricing and reimbursement strategies. Vidya Ramesh is an associate director at MKTXS, with multiple years of experience in market access and pricing/ reimbursement.

The Hill

Drug Importation has widespread implications on access

en. Bernie Sanders just introduced a bill that would enable Americans to import medicines from our northern neighbor.

The bill’s proponents argue that importing drugs from Canada would compel U.S. companies to lower their own drug prices. Unfortunately, that argument falls apart under scrutiny. Importation would expose Americans to drugs that have not been as stringently regulated as the current status quo, and curb future medical innovation.

For starters, importation wouldn’t save Americans much money. The surgeon general’s office estimates savings of just 1 to 2 percent of total U.S. prescription drug spending.

Why such comparatively minor savings? One reason is that Canadian drug prices aren’t as low priced as they appear. Consider Crestor, a cholesterol medicine that Sanders said cost roughly five times more in America than it does in Canada.

The assessment compares U.S. list price to the actual price paid by the Canadian government-run health insurers. In America’s market-based pricing system, private insurers and pharmacy benefit managers negotiate steep discounts off drug list prices. In the case of Crestor, discounts take 60 percent off the list price.

Importing Canadian drugs wouldn’t considerably impact patient’s’ medical bills — co-pays and patient contributions toward drug costs are largely determined by insurers and pharmacy benefit managers — but it would have an extreme impact on their safety.

Canada only monitors the safety of drugs intended for Canadian consumption. Its government admits that it cannot guarantee that medicines shipped to the United States are safe.

That’s cause for alarm — especially considering that many drugs from “Canadian” pharmacies actually originate in countries with less stringent safety controls. Such drugs can be inaccurately labeled or transported at improper temperatures.

It’s happened before. A few years ago, Canada Drugs — a major Canadian online pharmacy — sent $78 million worth of counterfeit and improperly handled drugs to doctors in the United States.

Sanders’s bill tries to address this problem by only permitting imports from registered Canadian pharmacies that receive a stamp of approvalfrom the U.S. Department of Health and Human Services. But if demand from American consumers proves overwhelming, even legitimate Canadian pharmacies may be tempted to cut corners and source potentially counterfeit drugs from developing countries.

Canadian officials would also likely oppose widespread importation. In the early 2000s, many Americans began ordering medicines from Canadian pharmacies. This created a drug shortage in Canada. Canadian officials introduced restrictions to curb these sales — and they’d no doubt do so again.

Importation also threatens the future health of Americans.

The United States is a world leader in drug development because our free-market pricing system rewards innovation. Of the 252 drugs approved by the FDA from 1998 to 2007, 117 were developed in the United States, according to a report from a former federal health official. The second-place country, Japan, developed 23 drugs. Canada and Australia combined created just seven medicines.

Most other nations, including Canada, artificially limit the price of medicines. If the United States were to permit widespread importation, it would effectively import price controls. The resulting reduction in revenues could compel firms to cut back on new research projects.

That would result in fewer new drugs — and more unnecessary deaths. New treatments are responsible for 86 percent of the decline in cancer deaths in recent decades.

Undercutting research firms could have dire economic consequences too. Pharmaceutical firms directly support over 850,000 U.S. jobs and generate $1.2 trillion in economic activity.

Americans need to consider the broader ramifications of a short-term decision to artificially lower drug prices. Importation risks forfeiting future cures and compromises the safety of the drug supply. Canada doesn’t hold the solution to our healthcare challenges.

Sandip Shah is the founder and president of Market Access Solutions. He spent nearly three decades working at large pharmaceutical firms, where he developed pricing and reimbursement strategies. Vidya Ramesh is an associate director at Market Access Solutions, with multiple years of experience in market access and pricing/reimbursement.

The views expressed by contributors are their own and are not the views of The Hill.


Gottlieb promises to accelerate drug approvals; surrogate endpoints can help

President Trump’s FDA appointee Scott Gottlieb wants to speed up the drug approval process to give patients quicker access to life-saving drugs.

Luckily for him, President Obama gave him the tools he’ll need to do so. In the waning days of his presidency, President Obama signed into law the bipartisan 21st Century Cures Act. The legislation permits the FDA to approve more drugs based on “surrogate endpoints.” This move will speed up the drug approval process and improve millions of Americans’ chances of beating cancer.

Scott Gottlieb has long favored quicker drug approvals as a way to save lives. In 2012, he claimed the FDA’s “hunger for extreme certainty about how drugs work” has done more harm than good. In other words, by demanding years of exhaustive clinical trials, the FDA prevents safe, effective drugs from entering the marketplace.

Surrogate endpoints are the answer Gottlieb is searching for. Surrogate endpoints sound complex, but the idea is relatively straightforward. Traditionally, FDA regulators don’t approve a drug until a pharmaceutical company shows that the medicine achieves the “clinical endpoint” — a metric such as increased three-year survival rates.

Hard endpoints, like overall survival, are considered the gold standard for measuring the efficacy of a cancer drug. But measuring overall survival endpoints takes years and requires large sample sizes of clinical trial patients. That’s often infeasible for medicines that treat rare, deadly cancers that kill in months.

So instead, the FDA is sometimes willing to approve drugs based on surrogate endpoints — how long the patient lives without the tumor spreading, for instance. Regulators believe that if a drug effectively delays the tumor, it also improves life expectancy. That probable cause-and-effect relationship is enough for the FDA to grant expedited approval to the drug and get it into dying patients’ hands.

Substituting surrogate endpoints for clinical endpoints shaves three and a half years off the drug development and approval process, according to FDA data. That accelerated timeframe can mean the difference between life and death for patients. By approving treatments for serious diseases right away, the FDA gives patients a fighting chance to beat their diseases.

Take Stage IV breast cancer. The prognosis is grim: four out of five women won’t live five years past their diagnoses.

But thanks to surrogate endpoints, one treatment, Afinitor, is making a difference. More than half of advanced breast cancer patients taking Afinitor in conjunction with another drug saw their tumors shrink or disappear, nearly twice as many as those taking the companion drug alone.

Overall, the treatment doubles the time patients live without the cancer worsening — a surrogate endpoint called progression-free survival.

Some medicines approved based on surrogate endpoints improve patients’ quality of life even for the rarest of diseases. Chronic lymphocytic leukemia is a rare type of cancer that afflicts 19,000 Americans each year.

Patients are seeing dramatic improvement with a drug called Imbruvica, which was approved based on surrogate endpoints. More than eight in ten patients saw their tumors shrink or stop growing, compared to 35 percent of patients treated with the current leading chemotherapy.

Because of the FDA’s already considerable reliance on surrogate endpoints, the United States leads the world in healthcare innovation. From 2003 to 2010, the FDA took just six months, on average, to approve new cancer treatments.[9] The European Medicines Agency — which waited until this past June to propose a significant use of surrogate endpoints— took nearly twice as long.

Across the Atlantic, patients don’t only wait longer for treatments; some medicines are unavailable altogether. The United Kingdom’s National Health Service, which provides most Britons’ healthcare, is reluctant to pay for drugs approved based on surrogate endpoints. In 2015, the NHS stopped covering 25 cancer drugs, including Afinitor. Most of those targeted rare or advanced cancers.

Medicare, by contrast, covers 80 percent of FDA-approved drugs.

Since it started approving drugs based on surrogate endpoints in 1992,  the FDA has shown it values innovation and is willing to cut through unnecessary red tape to quickly deliver breakthrough treatments to patients. The new legislation gives Gottlieb and his team authority to make even greater use of these surrogate endpoints. That’s sure to give cancer patients more time with loved ones and a new lease on life.