Issue No. 32: The U.S. Is Developing Innovative Medicines in Abundance, to FightCancer and More

Oscar Wilde once defined a cynic as “a man who knows the price of everything and the value of nothing.” The same might be said for some who comment on the price of medicines. They often forget the value: the lives enhanced and saved.

The year 2017 was “an extraordinary year in the history of medicine,” wroteBernard Munos, a senior fellow at FasterCures, a center of the Milken Institute. “It was the year when scientists beat cancer, and U.S regulators approved the first therapy to fix a faulty gene.” He continued:

It was the year when scientists beat cancer, and U.S. regulators approved the first therapy to fix a faulty gene. It was also a year that kept us enthralled with a quickening drumbeat of breathtaking news detailing spectacular advances – trials seemingly curing patients of hemophilia A and sickle cell anemia, and breakthroughs raising similar hopes for Huntington’s disease, Lou Gehrig’s disease, and even HIV.

Those aren’t the only breakthroughs last year. The FDA approved a new treatment for a specific form of Batten disease, a rare disease that can cause progressive neurological impairments and more treatments are under development by several companies.

Munos writes, “What is remarkable about these successes is that they are not just lucky breaks, but the products of new technologies that are ushering us into a new therapeutic space of vastly expanded possibilities,”

It appears that 2018 will continue the innovation hot streak. So far this year, the Food & Drug Administration (FDA) has approved 21 new drugs, and the pace seems to be accelerating – 12 were approved in the two-month span from mid-May to mid-July. In 2017, some 46 drugs were approved by the FDA’s Center for Drug Evaluation and Research (CDER), the most in over 20 years. Theaverage over the past 10 years has been 31 drug approvals.

A Striking Variety: From Smallpox to
Melanoma to Migraines

What first strikes you in examining the latest list of new drugs is the variety. The most recently approved was TPOXX, the first drug to treat smallpox. Thanks to widespread vaccination, in 1980 the World Health Organization declared smallpox, which is highly contagious and sometimes fatal, eradicated. But, said an FDA press release, “there have been longstanding concerns that smallpox could be used as a bioweapon.” Now we can treat it.

On June 27, the FDA approved two drugs – Braftovi and Mektovi – to treat unresectable or metastatic melanoma. (An unresectable cancerous tumor is one that cannot be removed through surgery; an “metastatic” indicates a cancer that spreads from one part of the body to another. Melanoma generally refers to skin cancer, the fifth most deadly form of the disease and often fatal if it metastasizes.)

Other drugs approved this year treat urinary tract infections, severe forms of epilepsy, moderate to severe rheumatoid arthritis, migraine headaches, opioid withdrawal symptoms, a rare form of rickets, plaque psoriasis, HIV patients with limited treatment options, cystic fibrosis, prostate cancer, and cancer of the gastrointestinal tract and pancreas.

Progress Against Cancer

Progress against cancer in recent years has been remarkable. In a report on new drug approvals, the FDA’s Janet Woodcock, who heads the CDER, wrote:

2017 was also another strong year for making new cancer therapies available to patients in need. Among others, we approved new therapies for certain patients with acute lymphoblastic leukemia; Merkel cell carcinoma; certain forms of relapsed or refractory acute myeloid leukemia; certain forms of lymphoma; recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer; and specific forms of liver, breast, and colorectal cancer. We also approved the first cancer treatment based on a genetic feature of a cancer rather than the location of the body where the tumor originated.

The American Cancer Society reports that since peaking in 1991 cancer death rates have declined 26% (through 2015), indicating that 2.3 million cancer deaths have been avoided. “This decline translates to nearly 2.4 million deaths averted during this time period.” Drug treatments are not the only reason for the dramatic decline. Americans are smoking less, and cancer is being discovered earlier, but pharmaceutical advances are the most important factor, accounting for 73% of survival gains.

There have been dramatic increases in five-year survival rates for cancers where treatments using a new and unique mechanism for treating the disease have been developed, including for prostate, lung, breast, and colorectal cancer. As a result, according to the American Cancer Society (ACS) the number of cancer survivors has risen from 9.8 million in 2001 to 15.5 million in 2016 and is forecast to reach 20.3 million by 2026.

Still, says ACS, “A total of 1,735,350 new cancer cases and 609,640 deaths from cancer are projected to occur in the US in 2018.” PhRMA, the association of biopharmaceutical companies, reported in May that 1,120 medicines and vaccines for cancer are currently in development by U.S. firms. All of those drugs “are in clinical trials or awaiting review” by the FDA. The average cost of developing a medicine that gains market approval in the U.S., according to the Tufts Center for the Study of Drug Development, is more than $2.5 billion, and some of the 1,120 cancer drugs will not be approved, but the sheer quantity and quality of research and development in cancer is staggering.

Some 132 drugs are in development for lung cancer, the leading cause of cancer death in the U.S., accounting for about one-fourth of the cancer mortality expected in 2018. Another 108 are being developed for breast cancer, the leading cancer diagnosed in women, with 266,000 new cases expected in 2018. Other drugs in the pipeline include: 137 for leukemia, 135 for lymphoma, and 90 for brain tumors.

Many of these new drugs deploy immunotherapy (which helped render Jimmy Carter free of melanoma that has spread to his brain) and personalized treatments. For example, CAR-T therapy genetically alters and boosts special immune cells to eliminate the disease. Says the PhRMA report:

A patient’s blood is filtered to remove T-cells, which are then altered in the lab by inserting a gene that codes for a receptor that targets a protein unique to cancer cells…. In 2017, the first CAR-T treatment was approved for certain pediatric and young adult patients with a form of acute lymphoblastic leukemia.

Last year, 16 of the 46 novel drug treatments approved by the FDA were personalized medicines, and 9 of those 16 were for cancer. Diagnostic tests are used to determine which treatments will work for which patient at the right time. In 2017, the FDA approved the first personalized gene therapies, two for blood cancers plus a personalized biosimilar medicine for HER2-positive breast cancer and the first approval for a medical based on a biomarker, no matter where the tumor is located.

Dramatic Decline in Heart Disease Death Rates

Declines in the death rate from heart disease in the U.S. is even more dramatic: a drop of 34% in deaths attributable to coronary heart disease from 2005 to 2015. The age-adjusted stroke rate declined 22% over the same period. Again, behind the improving statistics is a combination of advances in prevention, diagnosis, and treatment. Drugs have been essential, including the use of the anticoagulant warfarin to thin blood and reduce the risk of a stroke, medicines to lower blood pressure, and cholesterol-lowering statins.

There are now 200 medicines under development for cardiovascular diseases, including 42 for heart failure and 23 for stroke, according to PhRMA. One medicine in clinical trials has the potential to reduce heart attack or stroke by inhibiting the bromodomain and extra-terminal protein, or BET. Another uses gene therapy to target a tissue repair and regeneration pathway. PhRMA also reports on a novel treatment being tested for the potential to reverse brain damage from a stroke:

The treatment, a combination of a human activated protein (a protein that plays a role in regulating anticoagulation) and human stem cells, is administered to patients within a few hours of having an ischemic stroke. The transplanted combination stem cells mature into brain cells, helping to reverse brain damage.

Potential Breakthrough Drug on Alzheimer’s,
Plus 84 More

Heart disease costs an estimated $300 billion a year – about the same amount as dementias like Alzheimer’s Disease, according to the Alzheimer’s Impact Movement, and roughly the same amount that Americans, including government and private insurers, spent on all prescription drugs in 2015. Imagine not just the personal and family benefits but also the economic gains that a medicine that could reduce Alzheimer’s by half would achieve.

While deaths from heart disease have been falling, deaths from Alzheimer’s have nearly doubled since 2000. Billions of dollars have been poured into research, but progress toward a cure, or stopping the advance of the disease, has been slow.

Between 1988 and 2014, some “123 potential medicines for Alzheimer’s were halted in clinical trials, while just four medicines were approved.” None of the approved drugs can prevent Alzheimer’s from getting worse.

Then on July 5, the U.S. firm Biogen and the Japanese company Eisaiannounced “positive topline results from the Phase II study with BAN2401, an anti-amyloid beta protofibril antibody, in 856 patients with early Alzheimer's disease.” The study showed that the drug slowed the progression of the disease and “amyloid accumulated in the brain.” (Amyloid is a protein whose build-up is associated with Alzheimer’s.)

The Biogen-Eisai medicine still has a Phase III hurdle to surmount before FDA approval, but as of last year there were another 84 medicines for Alzheimer’s under development. Effective treatment is urgently needed. Alzheimer’s early costs could reach $1.1 trillion by 2050 and, experts say, “could single-handedly bankrupt Medicare in a matter of decades.” But if a new treatment were introduced in 2025 that delays the onset of Alzheimer’s by just five years, it “would reduce the number of individuals affected by the disease by 5.7 million by mid-century and save all payers, including Medicare, Medicaid and families, more than $220 billion within the first five years,” according to a study titled “Changing the Direction of Alzheimer’s Disease.”

A Robust Pipeline

No one can tell for certain which drugs will be approved when, but a monthly update by Prime Therapeutics, a large pharmaceutical benefit manager (PBM), in June listed 27 medicines for which the FDA is likely to make a decision before the end of the year. Again, the variety is striking. There are drugs for schizophrenia, dry-eye disease, malaria, acne, ADHD, pneumonia, HIV, postpartum depression, and many more. Another PBM, Optum Rx, has compiled a list of dozens of medicines in the current pipeline, including treatments for anorexia, Parkinson’s, breast and lung cancer, autism, liver cancer, leukemia, asthama, tuberculosis, and more.

Generics and Biosimilars, Plus Comparison
With Europe

Meanwhile, the FDA last year approved 1,027 generic drugs, 214 more than the record set the year before. Generics help keep a lid on overall drug spending, and, under Commissioner Scott Gottlieb, the FDA is instituting reforms to spur generic competition.

Gottlieb on July 18 announced a “Biosimilars Action Plan,” which, he said in a speech, “is aimed at promoting competition and affordability across the market for biologics and biosimilar products.” Biosimilars are treatments based on biological products, which in turn are composed of proteins, nucleic acids, or living entities such as cells and tissues. Biological products are among the most advanced and innovative treatments, and, because of their complexity, among the most expensive. They represented, as Gottlieb noted, 70% of the increase in drug spending between 2010 and 2015.

Savings from the introduction of biosimilars “range from $54 billion from 2017 to 2026 according to a study by RAND, to as much as $250 billion from 2014 to 2024,…according to a survey by Express Scripts,” said Gottlieb. But the pathway to market for biosimilars has been difficult. Fewer than one-third of FDA-approved biosimilars are actually available in the market. (We’ll discuss the Biosimilars Action Plan in our next letter.)

The FDA has approved a total of just 11 biosimilars, but the pace is quickening; five were approved in 2017 and two so far in 2018. The U.S. lags far behind Europe, which approved 16 biosimilars in 2017 alone.

Europe, however, lags far behind in developing innovative new medicines. A study published in March in JAMA by Irene Papanicolas, Liana Woskie, and Ashish Jha of the Harvard T.H. Chan School of Public Health, found, “With respect to a measure of innovation, the United States and Switzerland had the highest number of new chemical entities at 111 and 26, respectively.” Nor is it an accident that, of the 11 countries studied, the U.S. had the highest pharmaceutical spending per capital, with Switzerland second.

Drug companies operate on a simple model: their current medicines generate profits that are then plowed into research and development for new medicines. Reduce the revenues and the profits, and it stands to reason that you will reduce R&D and access to the flow of new medicines, which, after all, are where the value and mercy lie.
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