One of the most significant but perhaps least understood breakthroughs in healthcare in recent years is the advent of biosimilars.

Biosimilars are drugs that are highly similar to the biologic drugs on which biosimilars are based.

When a biopharmaceutical company’s patent or exclusivity protection for its biologic drug expires in the United States, biosimilars that have received U.S. Food and Drug Administration (FDA) approval can then enter the marketplace and compete with that existing drug.

Experts say that biosimilars, which go through a rigorous review by the FDA, provide the very same benefits for patients as the original drug and demonstrate no clinically meaningful difference from the existing biologic drug in terms of safety, purity, or potency.

In an exhaustive review of science literature evaluating patients who switched from biologic medicines to biosimilars, Hillel Cohen, executive director of scientific affairs at Sandoz Biopharmaceuticals (a Novartis company), and her fellow researchers looked at 90 biosimilar studies that enrolled 14,225 patients.

The results showed that safety concerns and efficacy were “unchanged” after patients made the switch.

“Biosimilars offer affordable options that increase access with no compromise in safety, efficacy, or quality,” Gillian Woollett, MA, DPhil, a senior vice president at Avalere Health and research scientist in immunology who’s worked for many years in the biotech industry, told Healthline.

Biosimilars haven’t yet had major impact in the U.S.

Sounds very promising. So why aren’t we hearing more about biosimilars?

Why haven’t they caught on in America like so many hoped?

There are several reasons. But perhaps the biggest is simply the public’s misunderstanding of what biosimilars are and what they do.

The first biosimilar approved in the United States was filgrastim-sndz (Zarxio) in early 2015 for the treatment of low white blood cell counts.

Filgrastim (Neupogen), the reference product, is manufactured by Amgen. Filgrastim-sndz, the biosimilar, is manufactured by Sandoz.

During the past three years, the FDA has approved 11 additional biosimilars.

But only three have actually been launched and marketed:

  • Sandoz’ filgrastim-sndz (Zarxio). It’s similar to Amgen’s filgrastim (Neupogen)
  • Pfizer and Celltrion’s infliximab-dyyb (Inflectra). It’s similar to infliximab (Remicade).
  • Samsung Bioepis and Merck’s infliximab-abda (Renflexis). It’s similar to Johnson & Johnson’s infliximab (Remicade).

According to Woollett, there are nearly 70 more biosimilars in the development pipeline. But if and when they’ll reach your doctor’s office is still anyone’s guess.

Woollett, who currently works on FDA regulatory strategy and policy, says that while the FDA alone cannot be blamed for the lack of availability and awareness of biosimilars, the federal agency can have a positive role in bringing biosimilars to the forefront of American healthcare.

“The FDA can make them available sooner using their vast experience with biotech and only asking for the data truly necessary to make review decisions,” Woollett said.

The FDA’s biosimilars action plan

This month, the FDA announced a new commitment to biosimilar awareness and acceptance.

FDA Commissioner Scott Gottlieb said the goal of the agency’s new Biosimilar Action Plan (BAP) is to increase public awareness and improve the review efficiency and predictability so that these products can reach patients and “help mitigate prices in the U.S. sooner rather than later.”

In an impassioned speech this month at the Brookings Institute, Gottlieb, a staunch supporter of drug deregulation, expressed his frustrations with the slow progress of biosimilars in the United States.

“These delays can come with enormous costs for patients and payers,” said Gottlieb, who added that biosimilars could save billions of dollars in healthcare costs in the United States.

“Biologics represent 70 percent of the growth in drug spending from 2010 to 2015. And they’re forecasted to be the fastest growing segment of drug spending in the coming years,” he said. “To make sure that the next generation of breakthroughs remains affordable, it requires vibrant competition from biosimilars.”

But is Gottlieb the right man to protect patient interests?

Some wonder if Gottlieb will adequately represent patients’ interests at the FDA, given his deep financial ties to pharma.

According to the OpenPayments database, Gottlieb received more than $400,000 in consulting and speaking fees from drug and medical device companies between 2013 and 2015.

That’s an extraordinary amount of money from the industry.

But Gottlieb’s support of biosimilars has a genuine, patient-friendly ring.

In his speech, Gottlieb said the FDA’s four key strategies for biosimilars are to:

  1. Improve the efficiency of the biosimilar and interchangeable product development and approval process.
  2. Maximize scientific and regulatory clarity for the biosimilar product development community.
  3. Develop effective communications to improve understanding of biosimilars among patients, providers, and payers.
  4. Support market competition by reducing gaming of FDA requirements or other attempts to unfairly delay market competition to follow-on products.

Biosimilars will offer more treatment options

Dr. Leah Christl, the FDA’s associate director for therapeutic biologics in the office of new drugs in the FDA’s center for drug evaluation and research, says the agency’s commitment to increasing awareness of biosimilars is all about the patients.

“With the cost of prescription drugs an ongoing concern in healthcare, the emergence of biosimilars offers more treatment options for patients, as well as much-awaited market competition that can potentially reduce costs for patients with serious medical conditions,” Christl said. “The agency is taking steps to more efficiently manage our review and licensure pathways to facilitate biosimilar competition.”

Christl says the FDA is educating clinicians, payers, and patients about biosimilar products and the rigorous evaluation they must go through.

Christl also notes that the FDA is modernizing regulatory policies to accommodate new scientific tools that can “better enable comparison between biosimilars and reference products that may reduce the need for clinical trials.”

Christl, who says that all information about biosimilar products can be found at the FDA website, told Healthline that the FDA is continuing to develop additional informational materials for patients, healthcare providers, and other stakeholders.

“We want healthcare providers to understand that the FDA undertakes a comprehensive evaluation to ensure that biosimilar and interchangeable products meet the respective rigorous standards for approval,” Christl said. “We also want to emphasize that healthcare providers and patients can expect that there will be no clinically meaningful differences between taking a reference product and a biosimilar when these products are used as intended.”

Biosimilars and cancer

While biosimilars have potential to treat all kinds of diseases, they could have a particularly profound impact on cancer.

Christl notes that many of today’s most innovative oncology treatments are biologics. These treatments come at a high and disproportionately increasing cost.

“While overall spending in the U.S. on prescription drugs increased about 5.2 percent in 2015, spending on oncology medicines increased about 18 percent,” she explained.

In 2005, biologics accounted for 32 percent of the $9.5 billion Medicare Part B drug program’s spending total. By 2014, this expanding category accounted for 62 percent of the program’s $18.5 billion total.

In September 2017, bevacizumab-awwb (Mvasi) became the first biosimilar anticancer drug to be approved in the United States.

Mvasi, which is similar to bevacizumab (Avastin), was approved to treat various types of advanced lung, brain, kidney, colorectal, and cervical cancers that Avastin is also approved to treat.

Three months later, the FDA approved trastuzumab-dkst (Ogivri) as a biosimilar to trastuzumab (Herceptin) for the treatment of breast or metastatic stomach cancer.

While both the FDA has approved both these treatments, neither is in the clinic.

According to a research letter published in July 2016 in JAMA Oncology, orally administered cancer therapies approved in 2000 cost an average of $1,869 per month, compared to $11,325 for those approved in 2014.

A May 2016 Health Affairs piece noted that the cost of treating cancer has risen to “unprecedented heights, putting tremendous financial pressure on patients, payers, and society.”

The article points out that from 2007 through 2013, “inflation-adjusted per patient monthly drug prices increased 5 percent each year,” and said there is currently “little competitive pressure in the oral anticancer drug market.”

“Biosimilars for oncologic use have the potential to bring welcome change to a field in much need of meaningful market competition and enhanced access to potentially life-saving therapies,” Christl said.

For some experts, biosimilar advancement is personal

Mark McCamish, PhD, president and CEO of Forty Seven Inc., is an international expert in biosimilars and biologics who’s worked as a senior executive at such pharmaceutical companies as Abbott, Amgen and Novartis-Sandoz.

McCamish told Healthline he’s passionate about educating the public about this lesser-known category of medicines.

“Several of my family members could have benefited from biosimilars had they been approved earlier,” said McCamish, who, while at Sandoz, was a key member of the team that helped filgrastim-sndz become the first biosimilar to be approved in the United States.

The drug, which addresses low white blood cell counts, helps people with cancer who are going through chemotherapy, among other conditions.

McCamish says biosimilar use in America has the potential to reduce the cost of pharmaceuticals overall, as biologic drugs are a major driver of pharmaceutical costs for payers.

“Reducing the costs of current biologics would likely increase access to these highly effective therapies, particularly earlier in the disease process, thus delaying or preventing some of the complications of chronic diseases,” he said.

In addition, McCamish says reducing the costs of current drugs allows for newer therapies with unique benefits to be more easily incorporated into clinical practice.

“For cancer patients, there are financial toxicities that dramatically increase a patient’s risk of going bankrupt,” he said. “Biologic treatments are becoming much more routine in the treatment of cancer patients, therefore, future use of biosimilars in the treatment of these patients can reduce the financial toxicities they experience.”

The anti-biosimilars movement

One of the reasons why biosimilars haven’t caught on in the United States is the anti-biosimilars movement waged by some pharmaceutical and biotech companies and their associated industry organizations.

“The anti-biosimilar campaigning was extremely well-funded, complex, robust, persistent, and involved attempts to influence physicians, patients, regulatory authorities, and payers,” McCamish said.

“Simple half-truths were extensively used, such as suggesting that biosimilars aren’t identical to their reference product, when they had full knowledge that there is inherent variability in biologic drug manufacturing such that their original reference product is not identical to itself from batch-to-batch manufacturing,” he said.

McCamish says the people involved in the anti-biosimilar effort were aware that simply suggesting that a biosimilar isn’t identical would trigger unfounded fears.

However, he notes it’s encouraging that the FDA’s Gottlieb is trying to help improve public health by trying to stimulate adoption and uptake of biosimilars in the United States.

He believes education is key for the future success of biosimilars in America.

“A physician or patient would not be able to tell whether they are administering the originator product or the biosimilar,” he said. “The products are approved to produce equivalent clinical outcome.”

A complex issue

But McCamish acknowledges that the biosimilars issue is complex and challenging.

“The terminology is not easy to explain,” he said. “Just take the term ‘biosimilar.’ Physicians and patients hear that it is only ‘similar’ and not ‘identical,’ so why should they use something only similar?”

McCamish says this is an unfortunate residual of regulatory terminology.

“It is impossible to use the term ‘identical’ since biologic manufacturing produces molecules with very slight differences, even in a single batch. That is, even the original drug has inherent small differences in the same vial,” he said.

“Therefore, the FDA could not use the term ‘generic’ or ‘biogeneric’ or ‘bioidentical,’ since this communicates that one biologic can be identical to another.”

McCamish would like healthcare personnel and patients to know that biosimilars are as close to the originator as the originator is to itself, considering manufacturing variability.

“There is inherent and acceptable biologic variability in manufacturing biologics,” he said. “Even the antibodies that we create in our own bodies in response to an infection are not identical molecules. There are slight variabilities that are well-understood and expected.”

Biosimilars vs. generic drugs

Another issue that biosimilar experts point to as a deterrent is the fact that biosimilars are often mistaken for generic drugs.

But they’re not the same.

Generics are generally small molecule-based, whereas biologics are typically large, complex molecules or mixtures of molecules that may be composed of living material.

As such, biosimilars aren’t exact copies of their reference products.

A generic drug, by contrast, has the same active substances and pharmaceutical form as its parent drug.

Biosimilars could save more than money

McCamish says that when patients and doctors in the United States embrace biosimilars, it won’t only save patients and payers money. It will potentially save lives.

“It’s becoming increasingly common to use a combination of biological agents in the treatment of cancer patients,” he said. “Using one biosimilar in combination with a newly approved biologic drug can reduce the costs of combination therapy, thus potentially providing additional life-saving therapies.”

The FDA’s Christl agrees.

“Biological products have revolutionized treatments for many serious and life-threatening conditions, but it can be financially difficult for patients when the right treatment for their condition or disease is a high-cost biological product,” she said. “Biosimilars have great potential for both patients and the entire healthcare system.”