The US FDA approval of Trastuzumab is a huge milestone for Biocon

First biosimilar Trastuzumab has been recently approved by the US FDA. Kiran Mazumdar Shaw, CMD, Biocon, reveals more an in an interaction

The US FDA approval for biosimilar Trastuzumab comes at a time when the global biosimilars opportunity is just beginning to open up. What does this approval mean for the Indian pharma industry in general and Biocon in particular?

The US FDA approval of Trastuzumab is a huge milestone for Biocon as well as the Indian biotech sector since this is the first biosimilar from India to be approved in the US. More importantly it is also the first biosimilar Trastuzumab to be approved by the US FDA. This approval is a validation of our development, regulatory and manufacturing capabilities in the complex area of biosimilar versions of monoclonal antibodies, which require advanced scientific capabilities and stringent quality controls.

This approval has established Biocon as a credible biologics player from India and has put us in an exclusive league of global biosimilar players.

It has also strengthened our resolve to focus on developing affordable biologics that can make cancer care both, more effective and more equitable around the world. It will spur us on our journey of developing advanced therapies that have the potential to benefit billions of patients.

After dominating the traditional generic drugs industry for decades, many Indian companies are now in the race to create generic versions of biologic drugs, or biosimilars, which are far more complex to make but offer a large global opportunity. As the first biosimilar from India to be approved by US FDA, this approval endorses the strength of our country’s science and the manufacturing capability to develop world class biosimilars. It demonstrates that Indian scientists, researchers and engineers are second to none and that Indian biopharma companies can produce advanced therapies that conform to best-in-class global quality standards.

What kind of challenges did Biocon have to surmount on the path to obtaining approval for biosimilar Trastuzumab from the US FDA?

We have had to traverse a long capital-intensive and research-intensive path to achieve this milestone. Developing a biosimilar is a highly expensive, complex and time-consuming exercise because it requires the confluence of multiple high-end skills due to the complexity involved in bioprocess development and significant investments in sophisticated manufacturing infrastructure including aseptic processing. This is because biosimilars are large and complex target-specific molecules, placed at the high end of the pharma value chain. Pharmacokinetic/ pharmacodynamic studies demonstrating biosimilarity against the chosen reference product are integral to the development process of biosimilars. Regulatory agencies also require comparative clinical assessments in phase III trials in a local setting.

While we cannot share molecule wise specific expense details, we would like to share that the cost of developing any biosimilar for global markets is estimated to be around $75-150 million in comparison to $2-5 million required to develop a generic. In addition, the investment required for setting up a biologics manufacturing facility ranges from tens to hundreds of millions of dollars. For example, it would take $200-500 million to build a large-scale biologics manufacturing facility versus $30-100 million to build a small molecule manufacturing facility.

Can you provide some insights into the development process for your biosimilar Trastuzumab?

The US FDA had, in January 2017, accepted for review our Biologics License Application (BLA) for the proposed biosimilar Trastuzumab. The submitted BLA included a comprehensive package of analytical similarity, nonclinical and clinical data. We generated robust data from the structural and functional characterisation of the molecule using multiple orthogonal techniques, nonclinical studies and pharmacokinetic evaluation in healthy subjects and patients and a safety, efficacy and immunogenicity study in relevant patient populations, which compared our biosimilar Trastuzumab to the innovator product. The clinical data consisted of two pharmacokinetic studies and the HERITAGE confirmatory efficacy and safety trial. In July, the FDA Oncologic Drugs Advisory Committee (ODAC) unanimously recommended approval of our proposed biosimilar Trastuzumab. Data presented to ODAC included results from analytical, nonclinical and clinical studies which demonstrated that our proposed biosimilar Trastuzumab is highly similar to the innovator product.

When will Ogivri get launched in the US market?

Our partner Mylan anticipates potentially being the first company to be able to offer a biosimilar Trastuzumab to patients in the US, as it has been able to secure global licenses for the product from Genentech and Roche earlier this year. This FDA approval is a key milestone, which will open up a clear pathway for Mylan to commercialise our biosimilar Trastuzumab in various markets globally.

In March 2017, Mylan had announced a global settlement and license agreement with Genentech and Roche on Herceptin. The settlement gives Mylan global licence to commercialise its Trastuzumab product in various markets around the world. However, as all other details are confidential we are not in a position to comment on commercialisation timelines.

What are the commercial terms with Mylan for the sale of biosimilar Trastuzumab in the US?

Mylan and Biocon have an exclusive partnership for a broad portfolio of biosimilar and insulin products. Our biosimilar Trastuzumab is one of the products that has been co-developed by Mylan and Biocon for the global marketplace. While Mylan has exclusive commercialisation rights in the US, Canada, Japan, Australia, New Zealand and in the European Union and European Free Trade Association countries, Biocon has co-exclusive commercialisation rights with Mylan in the rest of the world. The two companies have a cost share and profit share arrangement. Biocon has also invested significantly in establishing global scale capabilities to manufacture Trastuzumab in India to address global needs for affordable biologics.

What are your sales estimates for biosimilar Trastuzumab in the US?

Biosimilars such as Ogivri are affordable biologics that expand access to cutting-edge targeted therapies for patients who are not able to afford expensive originator biologic products. The product can help in enhancing patient access to biosimilars and deliver substantial savings to the US healthcare system. In the US, an estimated 250,000 new cases of female breast cancer and 28,000 new cases of stomach cancer are expected to be diagnosed in 2017 alone. Approximately 20 per cent to 25 per cent of primary breast cancers are HER2-positive. You can gauge the market opportunity by the fact that Herceptin had US sales of more than $ 2 billion for the 12 months ending September 30, 2017.

What kind of competition do you expect from other players for biosimilar Trastuzumab in the US?

According to the public information available, three other players have made regulatory submissions seeking approvals for biosimilar Trastuzumab in the US.

Do you have plans to launch biosimilar Trastuzumab in other markets?

Biosimilar Trastuzumab, co-developed by Mylan and Biocon, is under review by regulatory authorities in Australia, Canada, Europe and several additional markets. It is already approved in 19 countries around the world and is being marketed in some of the emerging markets including India.

How soon are you likely to launch biosimilar Trastuzumab in EU?

The EMA has accepted for review our partner Mylan’s Marketing Authorisation Applications (MAA) for the proposed biosimilars of trastuzumab and pegfilgrastim.

These applications were resubmitted upon completion of the Corrective and Preventive Actions (CAPAs), including the modifications of our aseptic drug product facility. We expect these CAPAs to be verified during inspection as part of the review process. We continue to work closely with our partner Mylan in engaging with EMA to provide these high quality, affordable therapy options for cancer patients in Europe.

We are ready for the re-inspection of our facility, however, cannot comment on the timing. We hope that the regulator will give us an early date.

Could you provide details on Biocon’s biosimilars pipeline?

Biocon has a broad portfolio of biosimilars under co-development with Mylan that includes insulins, monoclonal antibodies and other recombinant proteins that will address critical chronic diseases such as diabetes, cancer and autoimmune disorders, and collectively target a global market opportunity of over $ 60 billion.

The two companies have one of the longest-standing partnerships in the global biosimilars space with a leadership position in the nascent industry.

While we have been able to obtain regulatory approval for our biosimilar Trastuzumab in the US, there has been significant headway in the clinical development programmes of some of the other molecules as well. Dossier submissions have been made for three, namely Trastuzumab, Pegfilgrastim and Insulin Glargine, in the regulated markets of the US, EU, Australia and Canada as well as in key emerging markets. These three products target a global market opportunity of about USD 18-20 billion at current innovator pricing. Among India biosimilars players, Biocon has the most advanced biosimilars pipelines targeted at a global patient pool.

Has the launch of Trastuzumab in India increased access for patients of cancer here?

CANMAb, which was introduced by Biocon in India in 2014, has been benefitting thousands of breast cancer patients. It is actually the world’s first affordable biologic Trastuzumab to be developed in India and launched at a highly discounted price in comparison with the originator product. With its introduction, patients in India gained access to a cutting-edge affordable biologic for HER2-positive breast cancer and with more products coming in, the market saw a drop in the prices of the originator brand as well. CANMAb, today ranks as the No. 2 brand of Trastuzumab in the country which has garnered a volume market share of 23 per cent which is up from 18 per cent volume market share in 2015. (as per IPSOS June 2017& June 2015, MAT data).

In 2016, Trastuzumab was further included in the NELM which ensures a uniform price for this life saving therapy. The entry of other players with their brands of Trastuzumab has turned out well for the patients as it has expanded the overall market for Trastuzumab in India with many more patients now being able to access this affordable therapy. As per IPSOS MAT June 2015 and 2017, the overall volume growth for Trastuzumab has been nearly 24 per cent from 57,921 units (June 2015) to 71,701 units (June 2017). Interestingly the total market size of Trastuzumab, in value terms however has declined which is an outcome of the recent price regulation.