Remdesivir in India: An unfolding story

As the world scrambles to find a way to prevent or cure coronavirus infections, medical experts are evaluating and working on every available lead. The government is also taking all required measures to ensure availability of medicines related to the COVID-19 treatment.

After the US President Donald Trump touted hydroxychloroquine as a game-changer in the fight against COVID-19, it grabbed attention across the world, including India. Especially since the price of the drug was also low. In India, each 400 mg tablet MRP is around Rs 13. For instance, it was recommended by the ICMR as prophylaxis for asymptomatic healthcare workers involved in the care of suspected or confirmed cases of COVID-19. They were recommended to take 400 mg twice a day on day one, followed by 400 mg once weekly for the next seven weeks. The total cost of this course, which comprised nine tablets came to only Rs 117. However, the latest research reports related to its efficacy have created confusion.

Remdesivir – a promising drug candidate

After hydroxychloroquine, Gilead Sciences’ Veklury (remdesivir), has emerged as one of the most promising drug candidates for the treatment of COVID-19 patients.

In view of the pandemic situation, on June 1, 2010, the Indian drug regulating authority, the Drug Controller General of India (DCGI) granted the marketing authorisation to Gilead Sciences’ anti-viral drug remdesivir injection 5 mg/mL and remdesivir lyophilised powder for injection 100 mg for the treatment of suspected or laboratory-confirmed coronavirus disease 2019 (COVID-19) in adults and children hospitalised with severe disease. And the DCGI has approved it for “restricted emergency use” as well.

Mohammad Shahbaz, President, Rab Di Meher, a national NGO for pharma and healthcare sector, informed, “It is a five days treatment, and each day one dose is given under the administration of qualified practitioners only.”

He also informed that in the case of COVID-19, there are four different stages of the disease. As per the global clinical trial update, the drug is effective only on the first two stages i.e. in the first stage, a person shows symptoms of COVID-19 within 2-14 days of coming in contact with the virus and in the second stage, it shows emergency warning signs. However, stages three and four, require intensive care units and critical intensive care units respectively.”

Ensuring remedisivir’s availability in India

To expand the supply of remdesivir across the globe, Gilead Sciences has signed non-exclusive voluntary licensing agreements with four Indian generic pharma manufacturers, namely; Cipla, Hetero Labs, Jubilant Lifesciences and Mylan as well as a Pakistani firm, Ferozsons Laboratories to manufacture and distribute remdesivir in 127 countries. These countries consist of nearly all low-income and lower-middle-income countries, as well as several upper-middle- and high-income countries that face significant obstacles to healthcare access.

But, reportedly, there are four to five Bangladeshi firms that have already started manufacturing the anti-viral drug remdesivir. Companies like Eskayef Pharmaceuticals and Beximco Pharmaceuticals have in fact launched their products for the COVID-19 treatment under brand names, Remivir and Bemsivir respectively.

However, in an e-mail response, Gilead Sciences clarified speculations related to the grant of manufacturing licenses of its remedisivir brand to Bangladeshi firms and stated, “Gilead has not provided a license to Beximco Pharma, Eskayef Pharmaceuticals or any other company in Bangladesh to manufacture remdesivir. Gilead cannot comment on or verify the authenticity or effectiveness of this product as it is not manufactured by Gilead or one of our licensed partners.”

Considering, the rising number of COVID-19 positive cases in the Maharashtra State, after (DCGI) approval for remedisivir in India, the Maharashtra Government had made an announcement that it will procure 10,000 vials of remdesivir drug from Eskayef Pharmaceuticals for a price $160 per vial i.e. approximately Rs 12000.  But, after the Gilead statement, the state government’s decision to procure the drug from Eskayef Pharma has been put on hold.

How are Bangladeshi firms manufacturing the drug?

Dr Gopakumar Nair, Patent Attorney and CEO, Gopakumar Nair Associates explained, “To understand and appreciate the background of pharma manufacturing from Bangladesh, one needs to visit the Doha Declaration of 2001, and the proceedings thereof. The resolution passed unanimously and the proceedings thereof. All LDC (Least Developing Countries) have been given exemptions from implementing Patent Law (TRIPs) up to 2033. These exemptions are further extendible as per the resolution. Consequently, Bangladesh, being an LDC, is free to manufacture, use, sell and export any patented product/molecule, without patent infringement concerns. Bangladesh-based pharma companies can export to any LDC country without any restrictions. Export to any other country which provides a Compulsory License (CL) from the importing country or a government order waiving the CL, can also be done by Bangladesh without violating the TRIPs provisions.”

Why is there a delay from Indian firms?

Kedar Upadhyay, Global CFO, Cipla informed, “We are working on all aspects of compiling the data related to manufacturing, safety etc., as requested by the DCGI. And it is likely that we will be able to launch the product in a few weeks’ time.”

Nair commented, “Gilead has given licenses to four Indian firms and their application for a licence for manufacturing and sale in India is reportedly pending with the CDSCO/ DCGI or they are yet to comply with needful formalities. I personally feel that the regulatory approvals to these companies must be cleared on the fast track, in view of the urgency and essentiality.”

He further elaborated, “In the meantime, there was a report that the Maharashtra Government is planning to import remdesivir injection from Bangladesh, where more than one manufacturer has started offering remdesivir injection, which is in the price range of Rs 5000 to Rs 6000 or thereabout. Simultaneously, and parallelly, a Draft Rules was notified by the CDSCO for allowing import of Remdesivir Injection on “compassionate grounds”. However, Section 107 A (b) states that ‘importation of patented products by any person who is duly authorised to produce and sell or distribute the product, shall not be considered as an infringement of patent rights’.”

But, he also emphasised, “duly authorised under the law” is not clearly defined as to which law. Assuming that this reference is to ‘Patent Laws’ and not ‘Regulatory Laws’, importation from Bangladesh companies may not be compliant. However, as per Section 47 (4) importation by the Government for the purpose of its own use or distribution in any dispensary…………..etc. is exempted from Patent Law provisions. This is over and above the exceptions/exemptions available to the Government under various sections of the Patents Act 1970, such as Sec 92, Sec 99 to 102. However, in the current critical context, it is not at all expected that the Government may be forced to invoke any of these provisions, since socially responsible manufacturers, whether they are innovators or licensees will cause delay or disruption in the availability of these life-saving essential medicines for the treatment of COVID-19 infections.”

Nair suggested, “With regard to the pricing, since Bangladesh is offering remdesivir injections at around Rs 5000 to Rs 6000, it can be expected from Indian manufacturers to offer at around the same or lower prices. Since the CDSCO came out with the notification expeditiously on compassionate grounds, we can expect the Indian manufacturers also to voluntarily fix the price compassionately. This is all the more possible because Gilead has left open the pricing option to the licensees themselves. While deeply appreciating the licensing action by Gilead promptly, it is for the regulators to follow up on grant manufacturing approvals expeditiously, relying on the safety and efficacy data of Gilead and submission of simple bio-equivalence data. At this time, the availability of the drug is of utmost importance. The voluntary fair pricing option should be left to the manufacturers considering the urgency of availability of the drug to critical patients. The NPPA may not be called upon to get involved at this early and critical stage. Price fixation by the NPPA is not called for at these times. Voluntary compassionate pricing option will be in the best interests of the patients, hospitals and the medical profession.”

What needs to be done by the government to ensure availability and affordability?

Shahbaz commented, “Eskayef Pharmaceuticals’ offer price is $160 per vial of 100 mg whereas, another firm from Bangladesh, Beximco Pharmaceuticals has offered at $65, which means in Indian currency it is approximately Rs 4, 800. It is noteworthy that this price from Bangladesh to India (Beximco) must be having a 100 per cent margin. Considering, the fact of profit margins, I strongly feel that in India it should be more or less around Rs 2500 per vial of 100mg. And, to ensure product availability in the country during the pandemic crisis, the NPPA should fix the price for both APIs and finish formulations.”

Harish Jain, Secretary, Karnataka Drugs and Pharmaceutical Manufacturers Association said, ‘COVID- 19 has proven to be an unprecedented pandemic with no clear cure in sight. Treatment so far has been mostly symptomatic and immunity building. Remdesivir innovated by Gilead Sciences, which is showing a fairly good promise in initial trials. The medical community has been eagerly looking forward to the availability of remdesivir. The DCGI has been generous and granted lots of waivers, which has reduced cost of development to a large extent and enables Gilead through its India Partners to launch the drug quickly for the benefit of masses.”

He continued, “Bangladesh has stolen a march over India by quickly launching the drug ahead of India and many patients I understand have procured the drug from that country by various means in hope of saving lives. In view of a large number of patients in India who do not have access to insurance schemes expected to consume remdesivir, Gilead should take a lead and refrain from excessive profiteering. In case the MNC, through its partners, fix an exorbitant price for this drug, the National Pharmaceutical Pricing Authority (NPPA) should step in and invoke the provisions of the Drug Price Control Order (DPCO) 2013 and fix the ceiling price which is fair both to the company as well as patients.”

Price of the raw materials for remdesivir

In the Indian market, the price of the remdesivir raw material is approximately $100 per gram and each vial contains 100 mg of lyophilised powder for infusion. Since it is a lyophilised product, it requires special excipients and involves a long and lengthy process. Therefore, the cost of the product increases significantly.

Lee Pharma, an Indian manufacturer that makes raw materials required for remdesivir, claims that it makes the material at one-tenth of the innovator’s cost. Venkata Reddy,  Managing Director, Lee Pharma said, “Recently, we obtained the export license for remedisivir, and have exported 500 grams of remdesivir’s raw material to Bangladeshi firm ACI Formulations (ACI FL), a subsidiary of Advanced Chemical Industries.

Speaking on the context of availability and affordability in India, BR Sikri, Chairman, FOPE and Vice President, BDMA suggested, “Considering the pandemic situation in the country, the government should directly procure the medicine in bulk from manufacturers as in the beginning the product may not be affordable for the common man.”

While giving an example, he pointed out that it should be procured in a way similar to what the government does for mass vaccination and immunisation. He said, “With this proposed move, I believe both patients, as well as manufacturers, will get benefitted. And it will also ensure that there is no scarcity of the medicine in the market. However, if people are able to buy (directly) at a higher cost then there is no issue in it. But we must think about the common man.”

The DCGI did not respond to queries on market availability of remdesivir in India, till the time the story was filed.

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