New Alternatives for Branded Biologics

We’ve all heard about generic drugs. They are time-tested and battle-proven medicines that are more affordable than their patented predecessors. Branded drugs consistently break new records for high treatment costs, while overall drug prices have increased faster than inflation for decades.

The prices can be scary. For example, Alexion’s Soliris is estimated to cost up to $600,000 per year and BioMarin’s Brineura at an incrementally higher $700,000 for a year of treatment.

The availability of non-branded copies provides hope that prices will be affordable for all stakeholders in the system. In recent decades, biologics had surged from only a small proportion of drug spending in the 1990s to 43% of total drug spending in 2019. Biologics are larger and more complex molecules compared to the aspirin and statin tablets of yesteryear.  Not only are they different from these small molecule drugs but they fall under a different approval regime — both for new biologic entities and biosimilars.

Biologics have emerged as one of the most important drug classes. In 2020, 5 of the top 10 drugs by revenue were biologics. This class of medicine merits a higher price tag as materials, manufacturing processes and research and development costs for biologics are greater than small molecule drugs.

However, one of the primary reasons biologics are so expensive is that they have few competitors. In contrast to generic small molecule drugs, it is difficult to produce a biologic equivalent of such a complex and challenging molecule.

Biosimilar Interchangeability

FDA approval of a generic drug is sufficient to be considered interchangeable with its small molecule reference product. However, in the biologics universe, a second step after a drug is approved as a biosimilar is required to support its interchangeability with its reference product in the United States. A copy of a biologic can be approved at two different levels. It can be a biosimilar, which may not be substituted for the reference product without the prescriber’s consent or it can be an interchangeable biosimilar, which can be substituted without the intervention of the prescriber.  

Additional work is required to receive approval as an interchangeable biosimilar in the United States, including a switching study that shows no impact on efficacy when the products are switched. When a product is designated as interchangeable, state laws will govern whether or not pharmacies can or must switch one product for another.  

Switching Study Design

Source: Boehringer Ingelheim

The first interchangeable in the United States was approved in June 2021. Viatris’ VTRS insulin glargine-yfgn (Semglee) for treatment of diabetes was granted interchangeable status by the FDA. The product will be available before the end of the year and Semglee will be granted 12 months of exclusivity.  

The interchangeable designation will allow pharmacies to switch the biosimilar for the reference product when a product is prescribed. State law supersedes this sanction; however, most states allow the substitution of an interchangeable product as long as the provider and, sometimes, the patient, are notified. A few states even require that a generic version be substituted for a brand version if it is cheaper.

Boehringer Ingelheim’s Cyltezo

Abbvie’s Humira also known as adalimumab has been one of the highest revenue biopharmaceutical and biologic products in the world. With sales of over $20 billion per year in 2020, this TNF-α inhibitor surges past other well-known biologics such as Rituxan and Enbrel that have less than half of the revenues. The product is approved in 12 different indications including Crohn’s disease, rheumatoid arthritis, psoriasis and ulcerative colitis, among others.  Despite being approved in 2002, Humira has maintained its intellectual property protection for almost two decades and successfully fended off competitors. The revenue opportunity has attracted others to the space in an effort to bring down the price for this critical biologic. One of the responses has been Boehringer Ingelheim’s Cyltezo® (adalimumab-adbm).

Boehringer conducted its VOLTAIRE-X Phase III clinical trial to obtain a biosimilar and interchangeable designation for its version of adalimumab. The trial examined the effect of switching between Humira and Cyltezo in patients with plaque psoriasis. Cyltezo was approved in August 2017 as a biosimilar for the treatment of multiple chronic inflammatory diseases and will be available for sale in July 2023. On October 15, the company announced that the FDA had granted its supplemental Biologics License Application (sBLA) for Cyltezo as the first interchangeable biosimilar with Humira. This latest approval designates it as Interchangeable across all of Humira’s indications.

The mission to develop a robust and thriving biosimilars market is underway. However, it has taken many years or hard work by companies, consumer advocates and the FDA to get here.  When generics were first approved, it took decades to be accepted but they now comprise 9 out of 10 prescriptions filled. Time will tell if Cyltezo contributes to the same milestone for biosimilars.

To view the full research report (PDF) here.