Special Report: The Battle For Biosimilars In India

[story updated] Biosimilar drugs hold out big opportunities for India’s drug companies. But the future is fraught with challenges. One key challenge is regulations.

What does this mean for countries like India, an emerging market for biosimilars? How will the evolving global regulatory environment on biosimilars impact patients?

Last month, both these questions came to the fore as the battle over biosimilars moved centre stage in this country in the wake of an interim order by the Delhi High Court, and then another decision by a Division Bench of the same court which took a different view.

Background

Swiss pharmaceutical giant Roche’s Trastuzumab is stated to be a biological drug used primarily for treatment of HER 2 positive breast cancer. In India, Trastuzumab is sold under the brand names Herceptin®, Herclon™ and Biceltis®.

Indian drug maker Biocon, in partnership with the US-based generic drug maker Mylan Pharmaceuticals, have come up with products which they argue is “biosimilar,” that is, a biological product that is highly similar but not same as the original biological product, i.e. the “biologics.”

India is an emerging market for biosimilars. Some of the big names in the biosimilar space in India include Wockhardt, Biocon, Intas Pharmaceuticals, Panancea, Reliance Life Sciences, Virchow and Dr. Reddy’s Laboratories.

Biosimilars are seen as the next big frontier because the originator biologics are extremely expensive and as patent protection for some of the biologics expire, many Indian biotechnology companies see a big opportunity to develop and market biosimilars at a lower cost than the original biologics.

Predictably, multinational pharma companies are not going to make it easy for Indian biosimilar-makers.

Roche took the matter to court. A legal battle has been going on since 2014.

Now the issue is back in news. The Delhi High Court, in its 25 April order, slammed India’s drug regulatory body and raised a lot of questions about the regulatory process leading to approvals granted to Biocon and Mylan’s medicines and slapped conditions on their sale.

The final outcome could potentially impact breast cancer patients. Unsurprisingly, the 25 April ruling got big play in the Indian media.

“Based on Roche’s plea, the Delhi High Court, in a keenly watched legal tussle, said the approvals to Biocon’s CanmaB AND Mylan’s Hertraz were ‘not on the basis of the adherence of the guidelines’ and ‘rules framed under the Drug Act,’ “noted the Economic Times, a leading Indian business daily.

The newspaper also noted that the court order had restrained the biosimilar makers from using data relating to the manufacturing process, safety, efficacy and tests till the time a final decision is taken on the issue of biosimilarity.

The interim order by the Delhi High Court allowed the Indian company and its US partner to continue with manufacture and marketing of their breast cancer drug but with conditions. It said Biocon and Mylan can sell their medicines only under their own brand names ‘CANMAb’ and ‘Hertraz’ and not as “biosimilar” to ‘Herceptin, Herclon, Biceltis’, the brand names of products by Roche.

The court’s conditions for allowing the sale and manufacture of affordable cancer drugs by Biocon and Mylan included certain restrictions on packaging and labelling.

“The final finding in this respect is yet to be arrived after the present suit is heard upon completion of the trial,” the Delhi High Court ‘s 25 April order said.

Predictably, Roche was happy.

Ulrike Engels-Lange, spokesperson for Roche Group, told Intellectual Property Watch: “The ruling sends a strong, positive signal that the development, manufacture and approval of biosimilars in India must be subject to rigorous clinical and regulatory standards as per the applicable law. The court has made clear that the approvals granted to these companies are not in accordance with the existing protocol for biosimilars and, therefore, their drugs cannot be considered biosimilars. If these products are not considered biosimilars, it is important to question if they have generated the data necessary to be considered as innovator products in their own right.”

“The order does not question the quality, safety and efficacy of the product, countered Kiran Mazumdar-Shaw, chair and managing director of Biocon, speaking to Intellectual Property Watch soon after the April 25 court order. “Nearly 5,000 patients have benefited from our drug.”

“Biocon and Mylan have conducted all regulatory requirements on the basis of which products were approved. The matter is sub-judice. So this is as much as we can state” she added.

The matter came up in the Delhi High Court, the second time in a span of about a week. On 28 April, there was another decision, this time by a Division Bench of the same Delhi High Court.

Now it was the turn of Biocon to be jubilant.

“The Delhi High Court Division Bench on April 28, 2016, has directed, that the position as prevailing till 24th April 2016 (i.e. before passing of the 25th April judgment by the Single Judge Bench) shall continue to operate till the next date of hearing.

We continue to manufacture and sell CANMAb ™ , which is in the interest of the thousands of Her2+ breast cancer patients in India who have been treated with this product. CANMAb ™ has undergone robust laboratory, pre-clinical and clinical comparability studies to demonstrate quality, safety, and efficacy of the product and has received all necessary regulatory approvals. Certain players are attempting to block the entry of affordable biologics in India in order to protect their economic interests. Biocon remains committed to providing access to high quality, affordable biologics for patients globally and will take all measures to ensure that patients in India are not denied this access,” according to a Biocon spokesperson reached by IP-Watch.

The Delhi High Court’s April 25 ruling had been vigorously critiqued by public health activists, India’s generic drug makers and their representative bodies.And health activists argued that it could potentially create fear and doubt in the minds of patients about Biocon and Mylan’s drugs and this would impact the growth of low-cost biosimilars.

Reacting to the April 25 court ruling, D G Shah, secretary general of the Indian Pharmaceutical Alliance, said

“The judiciary has exceeded its area of competence,” he said. “It has taken upon itself the matters that drug regulatory experts are struggling with across the world. The ruling would also mean that a biotech product made by one company in two different plants is not the same. They are different. The drug approval will have to be specific to each manufacturing location. Likewise, a product made in the lab for approval and then scaled up for commercial production is also not the same!”

“Whether biosimilar or the follow-on biologic can be compared with the originator’s product and promoted as substitute is for the technical experts to decide, not the judiciary,” said Shah. “The Indian drug regulator is within his rights to frame and periodically re-frame its rules and guidelines. He is not bound by the rules and processes laid down for the approval of biosimilars by the developed countries.”

Health activists associated with the Campaign for Affordable Trastuzumab in India are happy that the April 28 decision of the Delhi High Court stays the earlier one. They say the issues coming to the fore should be viewed in the context of the challenges facing Indian producers of more affordable biological medicines face. A key challenge is litigation, as from the Swiss pharma company Roche.

“By linking intellectual property to the regulatory approval which is inclusive of the package insert, the court’s decision opens the door to vexatious litigation by the multinational bio-pharma industry against emerging domestic competitors. It is also against India’s position at the global level that linkage of IP (intellectual property) to the regulatory process is tantamount to TRIPS-plus,” a public health activist told Intellectual Property Watch.

The World Health Assembly (WHA) in 2014 called on governments and regulators to improve public access to affordable biosimilars, saying the price of medicines can be ‘catastrophic.’

The resolution made at the 67th annual WHA, the decision-making body of WHO (World Health Organisation), urges WHO member nations to strengthen national regulation to meet public health needs for biosimilars, to encourage scientific expertise and develop “solid, scientifically-based regulatory frameworks” for access to affordable, safemedicines, and to ensure new regulations do not prevent access to quality, affordable biologics, including biosimilars.

But how exactly this will be achieved remains a highly contested terrain.

One industry analyst told the Business Standard, an Indian newspaper: “The challenge that you face in biosimilars is the quantum of clinical trials that the regulator will ask you to do in various geographies. Let us assume, even if it is a smaller, limited set of trials if you have to do in Europe or the US, that will negate the entire cost advantage that Indian companies have.”

Last month, India released new guidance for biosimilar developers. The new document is a modification of previous guidance issued in 2012, but includes several important changes. These are now up for discussion.

And as the Delhi High Court’s most recent decision shows, the last word on this has not been said. The next hearing is likely to be on 10 May.