Clinical trials for oncology biosimilars: for which indications can we expect approvals?

2nd February 2018 (Last Updated February 2nd, 2018 10:18)

Over the past few years, biosimilars have been a hot topic in autoimmunity, and development has recently gained significant momentum in the oncology sector. With the first biosimilar approvals in oncology won in 2017, GlobalData expects this topic to gain significant attention in the year to come. While many questions regarding pricing, reimbursement, uptake, and acceptance among patients and oncologists are yet to be answered, the FDA and EMA guidelines on product development and approval have made significant progress in recent years.

Over the past few years, biosimilars have been a hot topic in autoimmunity, and development has recently gained significant momentum in the oncology sector. With the first biosimilar approvals in oncology won in 2017, GlobalData expects this topic to gain significant attention in the year to come.

While many questions regarding pricing, reimbursement, uptake, and acceptance among patients and oncologists are yet to be answered, the FDA and EMA guidelines on product development and approval have made significant progress in recent years.

The approval of a biosimilar is based heavily upon analytical data to establish similarity to a reference product. Unlike generics, these products require clinical testing in a Phase III trial to establish safety, efficacy, and immunogenicity. While some products are studied in multiple indications, many are conducted in only one or two key indications.

In this article, GlobalData assessed the indications for Phase III trials underway for the four most advanced biosimilar products in oncology: bevacizumab (biosimilar to Roche’s Avastin), cetuximab (biosimilar to Eli Lilly’s Erbitux), rituximab (biosimilar to Roche’s Rituxan), and trastuzumab (biosimilar to Roche’s Herceptin).

Indications for Phase III trials

Figure 1: Phase III clinical trial development for oncology biosimilars, by indication.

Among the four agents analyzed, Avastin has the largest number of approved indications: colorectal carcinoma (CRC), non-small cell lung cancer (NSCLC), glioblastoma, renal cell carcinoma (RCC), various gynecological cancers (cervical, ovarian, fallopian tube), and peritoneal cancer.

Although there are no Phase III clinical trials in six out of eight of the approved indications for Avastin, using the concept of extrapolation, biosimilar developers may cast a wider approval net by using data from the originator product.

Extrapolation is not automatic, it requires biosimilar developers to address key questions regarding the mechanism of action, pharmacokinetic / pharmacodynamics, immunogenicity, and potential differences in safety across patient groups. Therefore, bevacizumab biosimilars may become available for multiple indications, at the discretion of the regulatory agencies.

NSCLCs and CRCs

Based on GlobalData’s analysis, companies are most keen to gain approvals for NSCLC and CRC. This is not surprising, based on GlobalData’s analysis, the NSCLC and CRC markets were estimated at a combined worth of $14.8 billion in the 7 major markets (US, France, Germany, Italy, Spain, UK, and Japan) in 2017 and hold a much greater share of the biologics market than the other approved indications.

Rituxan is approved for chronic lymphocytic leukemia (CLL) and Non-Hodgkin’s lymphoma (NHL). However, most Phase III development underway for biosimilars is in NHL, diffuse large B-cell lymphoma (DLBCL, a lymphoma that includes NHL), and various other rare forms of lymphoma. Few trials are currently underway in CLL.

As expected for trastuzumab biosimilars, most development is for breast cancer. Herceptin is approved for HER2-overexpressing breast cancer or HER2-overexpressing gastroesophageal junction (GEJ) adenocarcinoma, however, sales are mostly garnered from breast cancer, which represents a much larger patient population than GEJ cancers.

For cetuximab biosimilars, very few Phase III trials are currently underway with only two Phase III trials, one in recurrent head and neck squamous cell carcinoma (HNSCC), and the other in unspecified cancers. As more trials are launched, GlobalData predicts that CRC will be an additional indication of interest for biosimilar companies looking to develop a cetuximab biosimilar, with Erbitux sales at nearly $1.0 billion in 2017 for the 7MM in CRC alone.

The need for extrapolation

As the world braces for more oncology biosimilars, extrapolation is likely to become a key topic of interest. Developers are not required to reproduce all data gathered from the originator product, rather, the onus is to sufficiently prove similarity to the originator, with thorough analytical studies and a limited number of in-human trials.

Some oncologists have expressed some level of discomfort with extrapolation, which will likely weigh-in on complex treatment decisions. Although evidence is likely to be strong for some indications, such as NSCLC and CRC, oncologists treating more rare conditions will need to weigh their comfort level against the affordability of biosimilars.