Patient Advocates Press to Ensure Safety and Efficacy of New Follow-on Biologics

Pending legislation that would allow the Food and Drug Administration (FDA) to approve and regulate “follow-on biologics” could dramatically impact millions of Americans who rely on biologic medicines to save or improve their lives.

At issue is legislation that would waive clinical trials and classify a follow-on biologic as interchangeable with its brand-name version—a move that affects patient safety, drug efficacy and patient access to approved medical treatments. Patient groups nationwide are calling upon Congress to act responsibly and cautiously as they establish standards for approving follow-on biologics.

The success of innovator or brand-name biologics
Biotechnology medicines (also known as innovator biologics) are large, complex protein molecules made using living cells by genetic engineering technology, a highly complex and expensive process that can vary from manufacturer to manufacturer. Biologics are among the most effective and expensive drugs available today. Millions of people, including those with dystonia, rely on these drugs. Two familiar examples of biologics are BOTOX (botulinum toxin type A) and Myobloc (botulinum toxin type B). 
 
Biologics greatly differ from traditional pharmaceutical medicines which are usually small, chemical molecules that are easily copied to create generic versions. A conventional pharmaceutical can be classified as a generic as long as it contains the identical active ingredients and has the same dosage as the original brand-name formulation. That’s why millions of people take generic drugs, which are significantly less expensive than brand-name drugs, knowing these medications are as safe and effective as the brand-name version.

Debate over follow-on biologics intensifies  
Follow-on biologics are potentially cheaper versions of the brand-name biologics currently on the market. Also known as “biosimilars,” follow-on biologics are similar, but not identical, to innovator biologics. Because they are created from living cells—and no two cells are identically alike—follow-on biologics can never be exact copies of their brand-name counterparts due to the complex nature of biologics and the varying manufacturing processes. Because the active ingredients in two biologics are never the same, the term “generic biologic” is inaccurate. The term “follow-on” indicates that a biologic is a second or subsequent version of the innovator biologic. Even a small difference between a copy and an original biologic can impact effectiveness and possibly cause serious side effects. Dosing levels between different versions of biologics also can vary, making it difficult for physicians to determine the proper dose from one biologic to another.

The debate surrounding the approval and use of follow-on biologics has intensified recently as innovator biotechnology medicines approach the end of their patent lives and pharmaceutical companies prepare to bring follow-on biologics to market. However, the FDA currently does not have an approval process in place for follow-on biologics. Lawmakers are now looking for ways to speed the approval of follow-on biologics in the hopes that these less expensive versions will create savings to the Medicare program. Legislation will determine two key factors that impact patient care: whether drug companies need to conduct clinical trials to ensure safety and effectiveness and whether health insurance companies and Medicare carriers can substitute a follow-on biologic for an innovator biologic without physician consent. 

The need for clinical trials
Patient advocates worry that rushing to approve follow-on biologics without requiring clinical trials (testing on humans) to guarantee patient safety and efficacy could be disastrous. Instead, they favor an approval process that includes rigorous scientific standards and requirements for clinical trial evaluations. Clinical trials are the only way to gather credible scientific data and assure physicians and patients that the prescribed medicines are safe and effective. Biologic or follow-on biologics that are not clinically tested pose a potential threat to patients who have no way of knowing how their body may respond to these medications, putting them at risk for serious side effects or possibly death.

The perils of interchangeability
Another major concern is the classification of innovator biologics and follow-on biologics as interchangeable drugs, meaning patients could receive a follow-on biologic without the consent of their physician. Since the active ingredients for two biologics can never be identical, patient advocates believe a follow-on biologic should never be considered interchangeable with an innovator biologic. If Congress or the FDA allows for interchangeability, pharmacies and health insurance carriers may require patients who are responding well to an innovator biologic to switch to a follow-on biologic to save money. The decision to prescribe a specific biologic (follow-on or innovator) should lie with physicians based on their own review of the clinical data and their own clinical judgment of what is best for their patients. Applying the same standards used for generic pharmaceutical drugs to follow-on drugs is inappropriate and potentially dangerous.

The risks of immunogenecity
Immunogenecity refers to the degree to which a medicine can cause an immune response, leading the body to develop a negative reaction to the medicine. The body may reject the medicine, attempt to destroy the medicine, or shut down certain systems within the body as a way to defend itself against the medicine. Patients who use biotechnology medicines are at greater risk of experiencing effects on their immune system. Production changes or impurities resulting from the manufacturing process of biologic or follow-on biologics can result in small differences in the medicines, which can impact immunogenecity and cause various responses in patients. Since different manufacturers have the potential to create follow-on biologics using varying production methods, the risk of immunogenecity with follow-on biologics increases.

A look at pending legislation
Among the legislation being reviewed by Congress is the Access to Life-Saving Medicine Act. This bill offers no data exclusivity for pioneers and does not require generic manufacturers to demonstrate that follow-on biologics are as safe and effective as the innovator products. This bill would permit interchangeability between brand-name and follow-on biologics. The Patient Protection and Innovative Biologics Medicines Act, on the other hand, offers 14 years of patent protection to pioneers and requires sponsors of follow-on biologics to conduct clinical trials to demonstrate safety, purity and potency.

Recent attempts to pass legislation failed because Congress could not reach a consensus on follow-up biologics. However, Congress is likely to pass follow-on biologics legislation in the next few months, providing patients and physicians with another opportunity to contact lawmakers about this important issue.

Time to take action
Now is the time to ask legislators to:

• Recognize the uniqueness of biotechnology medicines and require generic manufacturers to conduct clinical trials and provide data to support their claims that the follow-on biologics are safe and effective.

• Classify follow-on biologics as non-interchangeable to protect patient safety and ensure patients and healthcare providers continue having access to previously approved innovator biotechnology medicines.

If adopted by Congress, these measures can protect the rights of patients to choose the best treatment options by ensuring access to safe and effective biologics.