Biosimilar Basics Part 4: How Are Biobetters and Biosimilars Different?

• Part 1: What are biosimilar drugs? 
• Part 2: Biosimilar naming conventions: Top 10 acronyms in drug pipeline content.
• Part 3: Getting biosimilars to market–what works and what doesn’t.
• Part 4: Biobetters and biosimilars: What’s the difference?

Biobetters are new molecular entities. They are engineered to have improved properties over the reference biologic. They are related to existing biologics by target or action, but they are deliberately altered to improve disposition, safety, efficacy, or manufacturing attributes. Where biosimilars are copies of the biologic, biobetters improve on the original biologic.

The FDA does not recognize or label products as biobetter drugs. These products are reviewed as new biologics under the 351(a) Biologics License Application (BLA) pathway.

For example, we’ve considered  an alternative pegylated filgrastim (such as Spectrum’s eflapegrastim¹, marketed under the brand name Rolvedon) as a biobetter of Neulasta (pegfilgrastim).

Let’s go back to the beginning for extra context.

Biologic: The original

A biologic is a new therapeutic: it uses the BLA to apply for FDA approval as a new drug. It originates from biotech processes. That means it may be produced from living organisms or contain components of living organisms. Biologics have patents. Once the biologic’s patent has expired, other manufacturers can start to create biosimilars. The biologic is considered a reference product on which the biosimilar is based. The biologic is priced at a premium.

What is a biobetter drug?

Biobetters is a marketplace term, not an FDA term. It’s a biologic, but it is manufactured to be better than the originator, like a second generation. It uses the BLA to apply for FDA approval as a new drug. It has chemical or molecular differences from the originator.

Biobetter drugs aim for the same target as the original biological, but they are deliberately altered to improve disposition, safety, efficacy, or manufacturing attributes. For example, extending the duration of effect, decreasing dosing frequency or minimizing undesirable side effects are all possible differences a manufacturer could want to improve. These differences are referred to as enhanced pharmacokinetics and pharmacodynamics. Biobetters can be priced at a premium, higher than the original biologic.²

Definition: Pharmacokinetics refers to the movement of drugs in the body. It pertains to how the drug is absorbed, how it is distributed in the body, how it is metabolized (localized in the tissues) and how it exits the body or excreted.

Definition: Pharmacodynamics refers to the effects of a drug and its mechanism of action. How does it do what it does? It’s what the drug does at the site of action.

One of the main benefits of biobetter drugs are the reduced drug development risks and lower production costs. Some of the research and development tests have been performed for the reference biologic. The mechanism of action is already known.³

Biosimilars: How do they compare?

A biosimilar is similar to its originator biologic. It uses an Abbreviated Biologic License Application (ABLA) to apply for FDA approval. The abbreviated approval process meets FDA’s rigorous standards to help ensure that all approved biosimilars are as safe and effective as their reference products. A biosimilar product is manufactured to work like its reference biologic — the original FDA-approved biologic is often called a reference product. A biosimilar has no clinically meaningful differences from its reference product. In other words, it is FDA-approved to be just as safe and as effective as the original biologic.⁴ A biosimilar cannot apply for its own patent because it is a copy of an originator biologic. It is priced lower than its reference biologic.

Biosimilars vs generics

A biosimilar aims to be a near-perfect facsimile of the biologic, like a generic in the small molecule space, but substantially more complicated structurally and from a manufacturing perspective.

A generic has the same active ingredients as its brand-name counterpart. An FDA approval of a generic means the generic manufacturer has shown, with clinical studies, that the generic performs the same way in the human body as the brand-name drug.

Biosimilars and generics are both versions of brand-name drugs. They can be manufactured after the brand-name drugs’ patents have expired.

A biosimilar won’t be identical to its reference product. It will be similar. But similar still gets the job done. Prescribers and patients should have no concerns about using biosimilars instead of reference products.

The bio product mix

Biologics provide important treatments for a wide range of conditions. While biosimilars provide some price relief, biobetters improve on the original reference drug. Health plans will need to use them all to meet the needs of members.

What’s next?

Learn more about how biosimilars help lower drug costs while maintaining patient care by visiting our Biosimilars page.

Want to talk about how adding them to your plan could benefit both you and your members? Contact us directly.

References

1. https://investor.sppirx.com/news-releases/news-release-details/spectrum-pharmaceuticals-provides-update-rolvedontm
2. Biobetters and the Future Biologics Market (biopharminternational.com). Accessed at: https://www.biopharminternational.com/view/biobetters-and-future-biologics-market
3. https://www.sciencedirect.com/science/article/pii/S135964462100369X#f0005
4. Biosimilar and Interchangeable Products. 10-17-17. US FDA. Fda.gov. Accessed at: https://www.fda.gov/drugs/biosimilars/biosimilar-and-interchangeable-products