Implications of biosimilars in clinical practice tackled

MANILA, Philippines - Pharmaceutical company Roche recently conducted a medical symposium where it invited doctors from various specialties such as medical oncology, rheumatology, endocrinology, gastroenterology, and nephrology for a scientific meeting about the opportunities and challenges of biotherapeutics in clinical practices.

Dr. Frank Anthony Scappaticci, Genentech/Roche associate group medical director, gave a thorough presentation on the implications of similar biotherapeutics (otherwise known as biosimilars) in clinical practice. His presentation was followed by an active panel reaction and discussion with local doctors.

Scappaticci’s talk centered on the research and production of biosimilars and how they work in clinical practice, including how they are manufactured, what risks are involved in production, their efficacy and safety, and the guidelines that are being drafted by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA).

The presentation was an important topic considering “innovative biologic drugs are in place for a wide range of oncological and non-oncological indications such as various cancers, arthritis, and allergy. A standard guideline is highly needed for implementation for biosimilar medications before they can be approved for clinical practice,” said Scappaticci.

Biologics and biosimilars

The first important step in understanding biologic and biosimilar drugs is to understand their meaning.

“A biologic drug is a medication whose active substance is derived from a living cell. An example would be insulin, which can be produced by a living organism such as a yeast cell that has been given the gene to make it produce insulin. This is a simple example of a biological drug. Many say that, due to the complex nature of biologic drugs and the diseases that they can treat, biologics may be the one of the most important health care developments of our time,” said Scappaticci.

A biosimilar medicine, on the other hand, is a medicine similar to a biological medicine that has already been authorized. The active substance of a biosimilar medicine is similar to the one of the biological reference medicine.

Biosimilar medicines are similar, but not identical to innovator agents. In this case biosimilar medicines are called such and not generics due to the fact that the cell line source and manufacturing of a biosimilar product is more demanding and complex than the production of the traditional generic medications accepted by most regulatory authorities. 

The manufacturing process determines the product and each manufacturing process from one company to another is different. Therefore, biosimilar medications can never be identical.

Biosimilars in clinical practice

While biosimilars try to provide a more cost-friendly choice to the established biologic medicine, the utmost concern is patient safety. These medications must undergo routine clinical testing. This is no short-cutting the clinical trials, Scappaticci emphasized.

“With biosimilars, pathways and guidelines to their approval need to be as strict and as thorough as the standards for any biologic. While the key concern of the players in the biosimilar medications field state that if the same burdens for proof of safety and efficacy are implemented as their innovator counterparts, they will be unable to significantly reduce costs. However, if they are not put in place, patients will be put at significant risk,” he said.

Scappaticci pointed out that it is important to have strict guidelines in place to ensure patient safety. It is not as simple or easy to create a biosimilar product as it is to create a generic for a chemical product.

There are a wide variety of biopharmaceutical products in the market that have a wide range of molecular complexity from small simple proteins to very complex glycoproteins which can have multiple functions (monoclonal antibodies) or are involved in different biologic pathways (interferons).

With any biologic, there needs to be appropriate head-to-head comparisons at the level of quality, preclinical, and clinical testing. “Only following extensively and adequately designed clinical and non-clinical Phase I-III studies can overall safety and efficacy of a similar biotherapeutic be fully established. Regulatory guidance will be necessary to guarantee patient safety and overall benefit/risk,” said Scappaticci.

Biosimilars and FDA approval in Phl

After the successful forum with key opinion leaders and doctors from various specialties in the Philippines, another talk was held with regulators from the Philippine Food and Drug Administration (FDA) last Nov. 21.

Scappaticci and Dr. Fabio Bisordi, Roche global regulatory leader, addressed the regulatory overview and the need for regulation in the country.

They presented information on key issues, including differentiating between the innovator drug, biosimilars, and intended biologics stating the EMA and/or World Health Organization (WHO) guidelines on biosimilar products, extrapolation of indication, interchangeability/substitution and pharmacovigilance/immunogenicity.

Both speakers recommended that EMA and/or WHO guidance be adapted for biosimilar approval pathways in the Philippines.

A draft of biosimilar guidelines was stated to be in process by the Philippine FDA but it is currently still under revision and approval before implementation.

Countries such as Malaysia, Singapore, South Korea, Taiwan, Japan, and Australia have already biosimilar plans/pathways in place while the Philippines, Indonesia, Thailand, Jordan, and New Zealand have draft biosimilar registration guidelines.

Further talks with specialists and key opinion leaders will be the next step to pushing the draft guidelines further toward approval and implementation.