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Biologic Generic Drugs Are as Safe and Effective, says Review

August 1, 2016
New generic versions of biologics are gaining FDA approval, and a new review suggests the drugs have similar efficacy and safety to their brand name counterparts.

Generic forms of biologics are beginning to break into the US market, and while manufacturers claim these “biosimilar” agents may not be as clinically safe or effective as their own name-brand products, a new study suggests otherwise.

Study finds generic versions of popular biologic agents to treat rheumatoid arthritis, among other conditions, are as safe and effective as brand name agents.A recent research review found certain generic copies of biologics were comparable in safety and efficacy to the name-brand drugs used today in the treatment of autoimmune disorders.1 The study, which was published in the Annals of Internal Medicine, makes a case for the validity biosimilars, products that soon could be available on the US market.

“Biosimilars have offered tremendous promise in reducing the burden of prescription costs for patients and third party payers alike,” G. Caleb Alexander, MD, an associate professor at the Johns Hopkins Bloomberg School of Public Health and co-director of the Johns Hopkins Center for Drug Safety and Effectiveness, told Practical Pain Management. “Our study provides a valuable first look at a large amount of evidence examining whether or not these products have similar safety and efficacy profiles.”

Biosimilars: Economic Alternatives for Autoimmune Disorders

In recent years, a number of tumor necrosis factor-alpha (TNF-α) inhibitors have been approved for the treatment of autoimmune disorders, including infliximab (Remicade, Janssen Pharmaceutica), adalimumab (Humira, AbbVie, Inc.), and etanercept (Enbrel, Amgen, Inc.).

These biologics are effective for the treatment of various conditions, including rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis, and inflammatory bowel disease (IBD).  

By 2017, biologic drugs will comprise 20% of the pharmaceutical marketplace.2 These drugs are traditionally expensive, though. For instance, 1 dose of Janssen Biotech, Inc.’s infliximab (Remicade) can cost anywhere from $1,300 to $2,500 dollars.

Despite new federal legislation greenlighting companies to push generic forms of these drugs, only 2 biosimilars have since been approved, specifically:

  • Zarxio by Sandoz, Inc., a biosimilar of Amgen, Inc.’s filgrastim (Neupogen)
  • Inflectra by Hospira, a biosimilar of Janssen Pharmaceutica's infliximab (Remicade)

Because of the complex manufacturing process used to design biologics, these newer products cannot be exact replicas of the reference drugs they emulate.3-4 The concern is that generic formulations may not be as safe or effective as the brand name biologics currently on the market.

Companies of these products, like Janssen Pharmaceutica, have issued their own official positions on the approval of biosimilars, stating:

“We fully support efforts to implement regulatory standards for the review and approval of biosimilars in which patient well-being is first priority. Janssen patients deserve safe and effective treatments that are backed by robust data sufficient to scientifically justify their use in each disease in which they are approved,” noted a press release from the company.

Review: Comparing Biosimilars to Biologics

Biosimilars are more available outside of the US, which means most randomized, controlled trials have compared biosimilars side-by-side with brand name drugs have been conducted in other countries.

In the literature review, Dr. Alexander and his colleagues dove into nearly 4,500 existing titles and abstracts, searching for robust investigations comparing the clinical efficacy, safety, immunogenicity, or pharmacokinetic bioequivalence of biosimilar agents to the original drugs.

The researchers only chose full text publications and excluded studies that dealt with “biomimics” – noninnovator drugs that were approved before biosimilar regulations were created. However, the researchers did not pose any restrictions on study design or cohort population.

Nineteen studies were used in the review. Three Phase III trials found comparable data on efficacy between biosimilars and biologics, with similar average Cmax and Cthrough values based on an 80% to 125% equivalence margin. Indeed, most Phase III trials in the review had similar treatment outcomes “if the 95% CI for treatment difference was within a ±15% margin at the specified time point,” and based on prespecified margins, all of the Phase III trials showed equivalence between biosimilars and original biologics—with some trials extending into 54-week assessments.5-6

“For most studies, the proportion of patients with treatment-emergent adverse events and the proportion of those with serious adverse events were similar between biosimilar and reference groups,” with most adverse events being mild to moderate in severity, like respiratory tract infections, latent tuberculosis, increased alanine aminotransferase levels, headache, cough, dizziness, et cetera, the authors reported.

“I think our study supports broadly the comparability of these products,” Dr. Alexander told Practical Pain Management, though he also noted that doctors still need more data to better understand the viability of biosimilars in various treatment scenarios, “for example the safety of switching patients from the branded to the biosimilar product.”

Switching Patients to Biosimilars

Switching patients en masse over to biosimilar products simply for their cost-effectiveness likely could become a contentious topic among doctors, especially in cases where patients already are responding well to the biologic they are using.7 Companies like Janssen note that biosimilar products are not “interchangeable,” a separate distinction established by the FDA, according to The Biologics Price Competition and Innovation Act (BPCIA) that was signed into law back in 2010.

“For the FDA to determine a biosimilar is interchangeable with its reference product, a manufacturer must demonstrate that the biosimilar is expected to produce the same clinical result as the reference product in any given patient,” said the company in an official statement. “In addition, the manufacturer must demonstrate the risk of alternating or switching between the reference product and biosimilar is no greater than the risk of using the reference product,” the company noted.

A few cited trials did include open-label extension phases, which did not find any difference in adverse events when patients switched from a reference biologic to CT-P13, a biosimilar of infliximab.8-9 But the noticeable lack of research on biosimilar therapies is something that needs to be remedied, said Dr. Alexander.

“It took some work to find the right data sources to answer or to address the right questions regarding these products, and certainly in the US we’re at our infancy,” said Dr. Alexander.

More Questions

Lastly, doctors will not be able to tell from this review whether biosimilar TNF-α products can be extrapolated to other patient populations, like psoriasis or IBD— something currently being investigated by the ongoing NOR-SWITCH Study.

When exactly these products will be available is also an uncertain since companies like Janssen are locked into legal disputes with generic manufacturers over patent claims.10

“These are billion dollar products, and there is a lot of money at stake,” Dr. Alexander told Practical Pain Management. “And I think there will continue to be differences in opinion regarding the appropriate role of these products in treatment. But I think our study provides a valuable first look at one important class of biologics, and we certainly find they are much similar than they are different.”

Last updated on: April 12, 2017
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