Biologic and biosimilar drugs: strategies beyond patents

Biologic drugs and biosimilars – officially approved subsequent versions of innovator products – have been a topic of heated discussion in the recent past, and the debate continues. With the global biosimilars market expected to grow to US$10 billion by 2015, it is bound to garner attention. Usually, the generics are expected to bring low-priced versions of the innovator’s products and the same is expected with the biologics. But the game is different from small-molecule generic drugs. There are unique challenges on the innovator’s and the biosimilars’ sides.

New trends

While historically patents are considered to be one of the strongest intellectual property (IP) rights protection tools, we are experiencing new trends, especially in the biologic drugs/medicine area. In this article, we are looking at the case of trastuzumab, used for the treatment of metastatic breast cancer – more commonly known as Herceptina in India – to see how much protection a patent could provide to the innovator to protect its rights.

Genentech, a member of the Roche Group, was granted Indian Patent No. 205534 for trastuzumab in 2007, which is marketed in India under the brand names Herceptina, Herclon and Biceltisa.

The 20-year term was set to expire in 2019. With six years still remaining, in 2013 Roche decided not to maintain the patent, did not pay the annuity fee for the 15th year term, and the patent ceased on 3 May 2013.

Strategic decision

This decision was taken even when there was apprehension that competitors would launch biosimilars of trastuzumab. It was reported that Roche took a strategic decision to let the Indian patent for trastuzumab lapse.

Soon after the lapse of patent, the Drug Controller General of India (DCGI) granted marketing approval to Biocon for a biosimilar of trastuzumab.

Roche went to Delhi High Court seeking an injunction against the approval, making the DCGI a party to the action. Interestingly, with an abandoned patent, and instead of going the patent infringement route, Roche decided to plead on non-compliance of regulatory procedures and passing-off.

The Guidelines on Similar Biologics for marketing approval of biosimilars were issued in 2012, and Roche showed that Biocon had obtained approval in respect of molecule trastuzumab-bulk in October 2013. Based on this, Roche pleaded that the approval was not granted under the Guidelines on Similar Biologics, as such approval on similar biologics could not have been granted in such a short period in view of the long prescribed procedure.

Biocon’s biosimilar, CANMAb, was expected to become available in India in the first week of February 2014. Roche pleaded that the biosimilar version of trastuzumab should be restrained from introduction into the Indian market until appropriate tests and studies as prescribed under the said guidelines had been conducted and appropriate approvals had been obtained.

The high court asked Biocon to disclose to the court the nature of the approvals of the biosimilar product obtained by it, and accordingly decided that no specific order of interim injunction was required, as Biocon was not entitled to introduce or launch the drug without the requisite approvals.

Second pleading

Roche’s second pleading was that the defendant had misrepresented the nature of its drugs as a “biosimilar trastuzumab” and a “biosimilar version of Herceptina”. Roche stated that such misrepresentations are in the nature of passing-off, since they seek to pass off the defendant’s drugs as being of the same quality and class as Herceptina, and the defendant would take unfair advantage of the reputation and goodwill enjoyed by the plaintiff’s brand Herceptina, and for the innovative and original product trastuzumab, in the Indian market.

The court agreed on this with Roche and restrained the defendant from relying upon or otherwise referring to Herceptina, or any data relating to trastuzumab marketed as Herceptina, and from claiming any similarity with Herceptina. The case is pending.

The above interesting strategy adapted by Roche indicates that the patent right did not come in very handy when it came to protecting its interests for its biologic drug trastuzumab. The challenges are to see whether a biosimilar – expected to be similar in terms of safety, efficacy and quality to the innovator, or reference biologic for marketing approval – would infringe a claim covering the innovator biologic, despite being structurally not identical to the innovator biologic.

It remains to be seen how much variation from the innovator biologic would still be considered within the claimed scope, and how much variation from the innovator biologic would still be considered as having enough similarity to pass the safety, efficacy and quality tests for marketing approval for the same use.

Price discounting

To remain competitive in the market, Roche also adopted the strategy of discounting the price of its drug for the Indian market. Roche also tied up with the Indian drug maker Emcure Pharma to offer the drug under the brand Herclon at a reduced price from that at which the drug was initially launched.

Unlike with generic drugs, where the innovators face a strong challenge in protecting their rights, the situation slightly tilts in the favour of innovators when it comes to biologics and biosimilars. The cost of development and approval for a biosimilar is much greater than for a small-molecule generic, and hence needs more investment and effort by the companies trying to enter the market with a biosimilar. Also, unlike small-molecule generics, a biosimilar may not necessarily be considered as a substitute for the innovator biologic, and the innovator biologic may still retain its market share in such situations.

Due to the basic nature of biologic drugs and biosimilars, there are uncertainties with respect to determination and assessment of patent infringements. Enforcement of patent rights may not be effective in every situation. Hence, the biologic innovators need to look beyond patents to remain competitive in the market.