How does a biosimilar get approved? What happens after that?

| Melissa Leavitt

With almost 10 different biologics approved in the United States for psoriatic disease, these therapies are delivering dramatic improvement to more and more patients—and giving doctors better tools for increasing patient satisfaction.

In the coming years, biosimilars will offer you and your patients even more treatment options.  

According to the U.S. Food and Drug Administration (FDA), “Biosimilars are a type of biological product that are licensed (approved) by FDA because they are highly similar to an already FDA-approved biological product […] and have been shown to have no clinically meaningful differences from the reference product.”

The “reference” drug is the already-approved biologic.

The first biosimilar—Zarxio, a biosimilar for Neupogen (filgrastim), a treatment used in cancer patients—won FDA approval in March 2015.

It was followed one year later by Inflectra, a biosimilar for Remicade (infliximab), which was the first biosimilar approved in the U.S. for psoriasis and psoriatic arthritis.

The second biosimilar approved for psoriatic disease is Erelzi, a biosimilar for Enbrel (etanercept), which won approval in August. FDA approval for a third biosimilar for psoriatic disease is expected soon (see the first question below).

Biosimilars have been available in Europe since 2007. In the U.S., Zarxio is already on the market. No biosimilars for psoriatic disease have yet to become available, but more approvals are expected, and a number of biosimilars for psoriasis and psoriatic arthritis are currently in development.

As we wait to learn more about how biosimilars could improve access to much-needed therapies, NPF is launching new programs to educate health care providers and patients on biosimilars. Stay tuned for webinars and other resources in the coming year.

Here, we answer your questions about the FDA approval process for biosimilars, how biosimilars compare to reference biologics, and what NPF is doing to make sure you and your patients have access to the best possible treatments.

Which biosimilars are approved for psoriasis or psoriatic arthritis?

In April 2016, FDA approved Inflectra, a biosimilar for Remicade (infliximab) developed by Celltrion. Like Remicade, Inflectra blocks the cytokine tumor necrosis factor-alpha (TNF-alpha). It was approved for use in several inflammatory and immune-mediated conditions, including psoriasis and psoriatic arthritis.

Another biosimilar that blocks TNF-alpha was recently approved for psoriasis and psoriatic arthritis too: a biosimilar for Enbrel developed by Sandoz known as Erelzi.

A biosimilar for the TNF-alpha inhibitor Humira (adalimumab) developed by Amgen, known as ABP501, received backing from an FDA advisory committee in July. A final decision regarding approval for ABP501 is expected in September.

What’s the FDA approval process like for biosimilars?

To be approved by FDA as a biosimilar, a drug must meet two criteria: it must be highly similar to the reference biologic, and it cannot have any clinically meaningful differences in terms of safety or efficacy from the reference biologic.

As Dr. Leah Christl, FDA’s associate director for therapeutic biologics, noted in the July 12 advisory committee hearing on ABP501, there is no “one size fits all” process for establishing biosimilarity. Rather than looking for a specific set of trial results, FDA considers the total data package when reviewing a biosimilar application.

The approval process for biosimilars is guided by stepwise evidence development. That means that the data generated as part of the development process is targeted to address specific uncertainties that emerge at each step of development.

Analytical data, which assesses the specific chemical make-up and other properties of the biosimilar, forms the foundation of an FDA biosimilar approval application. Looking at amino acid sequence, bioactivity, glycosylation and other attributes, this is the data that’s used to prove that a biosimilar is highly similar to a reference biologic.

Based on the questions that still remain after the analytical testing, data is also generated through pharmacological studies, animal studies to test toxicity and clinical studies comparing the safety and effectiveness of the biosimilar to the reference biologic.

Isn’t that different from the way most drugs are approved?

Yes. The process is referred to by FDA as an “abbreviated licensure pathway.” It was created by the Biologics Price Competition and Innovation Act of 2009, passed as a provision of the Affordable Care Act.

Although the approval process is abbreviated, the process still requires an extensive amount of data to be submitted with the application, Christl noted on July 12. This data emerges through a different development process than the data used in standalone drug applications.

Standalone drugs move through three phases of clinical trial testing on their way to approval. Phase I is typically a safety study in a small number of people, and Phases II and III test the effectiveness and safety of the drug in a larger patient population.

For biosimilars, because the bulk of the data comes through analytical studies supporting the similarity of the drug to the reference biologic, the clinical trial phase starts at Phase III.

FDA allows the use of data from the reference biologic in support of a biosimilar application. That’s important to keep in mind when considering the practice of extrapolation—when data is extrapolated from one condition to support a drug’s use in another condition.

A biosimilar can be approved for use in a certain disease even if it has not been specifically tested in that disease—as long as the reference biologic is approved for the treatment of that disease, and the scientific data behind the biosimilar application can support it.

Inflectra, for example, was approved for the treatment of psoriasis and psoriatic arthritis, even though the data application only included comparative studies in rheumatoid arthritis and anklylosing spondylitis. ABP501 and GP2015 both included psoriasis studies in their data packages.

How do clinical trial results for biosimilars compare to their reference biologics?

The hearings for ABP501 and GP2015 both included data from comparative studies with the reference biologic in people with psoriasis. In both cases, FDA found no clinically meaningful differences—the standard for biosimilarity—between the biosimilar and the reference biologic.

For example, according to FDA’s presentation on July 12, studies for ABP501, which included 350 moderate to severe psoriasis patients, found that people on the biosimilar experienced about an 81 percent improvement after four months, as measured by the Psoriasis Area and Severity Index (PASI). People with psoriasis taking Humira experienced an average of 83 percent improvement.

On July 13, FDA presented data involving 531 moderate to severe psoriasis patients comparing their PASI improvement after three months. According to the data, patients on GP2015 experienced 82.6 percent improvement on average, while patients on Enbrel experienced almost 82 percent improvement.

Other studies have also found no meaningful differences between biosimilars and the reference product in terms of safety and efficacy.

A study published in July in the Journal of the American Academy of Dermatology tested the effectiveness of Inflectra (which goes by Remsima in Europe) in a group of Italian patients with psoriasis.

According to the results, researchers found that patients who switched from Remicade to Remsima did not experience any change in clinical response or adverse events through a median follow-up time of about six months. The same study found that, out of a group of five patients on Remsima who had never taken Remicade, four achieved 75 percent PASI improvement after 10 weeks of treatment.

Another study, published in August in the Annals of Internal Medicine, reviewed results from 19 different studies of biosimilars, including biosimilars for Enbrel, Remicade and Humira. Overall, according to the researchers, results indicated that the biosimilars and the reference biologics delivered similar efficacy, and most studies showed similar rates of adverse events.

When will biosimilars be available to patients?

Following a court ruling earlier this month, Inflectra could become available within the next few months. A pending court case could affect the availability of Erelzi.

Are biosimilars considered interchangeable with biologics?

So far, no biosimilars have been approved by FDA as interchangeable with biologics, and FDA has not yet offered guidance on what the standard of interchangeability will be. A guidance on interchangeability has been expected for several months.  

Will a biologic be switched to a biosimilar without my knowledge?

Some participants at the July 12 hearing raised the question of whether drugs that are not considered interchangeable, such as a biosimilar and a biologic, could be switched at the pharmacy without notifying the doctor or patient.

If a biosimilar is not approved as an interchangeable biosimilar, it may not be substituted for the original biologic at the pharmacy counter.  However, a lack of interchangeability would not prevent a pharmacy benefit manager from removing a particular biologic from their formulary and replacing it with a biosimilar, as CVS Health has announced it will do with Zarxio in 2017. Such a formulary change may result in a defacto shift off the biologic on to the biosimilar. NPF is currently reaching out to CVS and other pharmacy benefit managers to understand the impact of these plans to stable patients.

Returning to the question of switching at the pharmacy counter, NPF’s government relations team has been working for several years on biosimilar substitution legislation which would address the issue of switching an interchangeable biosimilar for the original biologic.

The legislation ensures that a pharmacist must communicate to health care providers if they switch a biologic to an interchangeable biosimilar. To date, 25 states and Puerto Rico have passed or are considering the interchangeable biosimilar substitution bill.

NPF is also part of a coalition of patient advocacy groups called Patients for Biologics Safety and Access that works to ensure that the decision to switch from a reference biologic to a biosimilar remains between the provider and the patient. Read more about the coalition’s approach to biosimilar switching here.

Read the official statement on biosimilar substitution from NPF’s Medical Board here.

How many biosimilars are being developed for psoriasis and psoriatic arthritis?

About 15 biosimilars for Humira, Enbrel or Remicade are currently being developed. We’ll continue to keep you posted as more biosimilars receive FDA approval. 

Where can I find more information?

NPF will be introducing webinars for patients and providers in the coming months. Click here for more information. In addition, our Patient Navigation Center can answer questions about biosimilars and access to other treatments.

Editor's note: in late September 2016, Amgen's biosimilar for Humira, called Amjevita (adalimumab-atto), won FDA approval. In October 2016, it was reported that Inflectra could come to market as soon as late November 2016.


Driving discovery, creating community

For more than 50 years, we’ve been driving efforts to cure psoriatic disease and improve the lives of those affected. But there’s still plenty to do! Learn how you can help our advocacy team shape the laws and policies that affect people with psoriasis and psoriatic arthritis – in your state and across the country. Help us raise funds to support research by joining Team NPF, where you can walk, run, cycle, play bingo or create your own fundraising event. If you or someone you love needs free, personalized support for living a healthier life with psoriatic disease, contact our Patient Navigation Center. And keep the National Psoriasis Foundation going strong by making a donation today. Together, we will find a cure.

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