On the night of June 8, Joel Pinto set out on an 18-hour drive from Chennai to Hyderabad and back, all for a single injection of 648 mg for his father, who was fighting Covid-19 in a Chennai hospital. The doctors had prescribed tocilizumab as critical to save Pinto’s father’s life, but they asked him to arrange the 800 mg vial of the medicine himself as they did not have it.
A local vendor had also offered the medicine but at the inflated price for Rs 1.5 lakh. Pinto chose to drive to Hyderabad as the vendor there offered a better price – Rs 92,672 – albeit for a smaller dosage than what doctors had asked him to get. This is the printed price on the drug.
For 30 days of hospitalisation, his father was handed a bill of Rs 10.26 lakh. Their medical insurance covered only Rs 4.5 lakh of the treatment cost. The Pintos had to spend Rs 6.6 lakh, including the cost of tocilizumab, which was not covered by insurance.
On the other end of the country in Delhi, Rajiv Dhawan, a Delhi-based entrepreneur, was also looking for tocilizumab for his 65-year-old uncle in Ahmedabad, who was in a critical condition, in May. “I began to get phone calls from people saying they were vendors and could offer this drug but at high prices. I had not contacted these people and I do not know how they got my number,” said Dhawan. “Though it seems like the injection is not available in stores, it is being sold in the black market at very high prices.” Dhawan was also told he could get 400 mg of tocilizumab for Rs 1.4 lakh. He managed to get the drug from three different vendors in Ahmedabad and Hyderabad for Rs 25,000 for 80 mg, Rs 32,000 for 400 mg, and Rs 42,000 for 400 mg.
Despite several reports about the difficulties in procuring tocilizumab, a spokesperson for Roche Products India Pvt Ltd, which manufactures the drug, told IndiaSpend, “As a policy, we do not share price details of any of our products.”
This report is part four of IndiaSpend’s series on the increase in prices of medicines and healthcare during the Covid-19 pandemic. This part looks at how poor drug supply regulations have further deteriorated during the Covid-19 pandemic.
For this, we examine the case of tocilizumab, a drug being experimentally used for Covid-19 treatment, but the breakdown of supply chains and black marketing apply to many other drugs, we found.
Tocilizumab and Covid-19
Tocilizumab is not a new drug, nor is it a “miracle drug” that could treat Covid-19. It has been around for long and used to treat mostly rheumatoid arthritis. It is undergoing clinical trials currently to ascertain whether it is a definitive treatment option for Covid-19. Right now, doctors across the world are taking subjective calls, based on their clinical discretion, on whether a patient should be administered the drug. This is known as “off-label use”.
But as tocilizumab’s importance grows and the scientific evidence around it comes in, there is a growing problem of supply and affordability. The main reason for this is that the Swiss pharmaceutical major Roche has a complete monopoly over who makes this drug. Currently, only Roche and its subsidiary Genentech make it. Roche has not licensed it out to any other company. In India, tocilizumab is imported and then distributed by the Indian generic drug company Cipla.
This keeps the price of tocilizumab high and the supply tight in India, while families in distress struggle to procure it.
How it works
While the SARS-CoV-2 virus causes Covid-19, once the virus manifests in the body, it attacks several parts of the body. Covid-19 is predominantly a respiratory tract infection. In its severe form, it escalates to acute respiratory distress syndrome, sepsis, septic shock and multiorgan failure such as of the kidneys and the heart.
In severe cases of Covid-19, the virus also causes an excessive activation of the body’s inflammatory response and an immune system malfunction known as a “cytokine storm”. In this situation, there is interference in the body’s normal cell function, which releases an excess of cytokines, causing a disproportionate level of inflammation. Such patients would find it difficult to breathe, despite being given oxygen.
Over the course of the Covid-19 pandemic, scientists began to consider tocilizumab as useful in severe Covid-19 patients who might experience a cytokine storm and to prevent them from deteriorating further. Tocilizumab could block some of this inflammation which causes the cytokine storm.
“If used correctly, tocilizumab could prevent a patient from suffering such serious damage to their lungs that they would need mechanical ventilation,” said Sushmita Roy Chowdhury, a pulmonologist at Apollo Gleneagles Hospital in Kolkata. At least 15 patients have been given tocilizumab at that hospital and the results have been largely positive so far, added Roy Chowdhury.
On June 13, the Indian government updated its clinical management protocol for Covid-19. For the first time, it included a section on investigational therapies, which said that doctors could prescribe tocilizumab, off-label, for some people with Covid-19.
The government’s guidance was specific: “Tocilizumab [off label] may be considered in patients with moderate disease with progressively increasing oxygen requirements and in mechanically ventilated patients not improving despite use of steroids. Long term safety data in Covid-19 remains largely unknown.” Doctors should especially note if the patient is showing raised markers of inflammation. These patients would also have to be carefully monitored for secondary infections, as tocilizumab leaves them prone to this, it said.
This document also acknowledged that there was a shortage of tocilizumab and other investigative drugs, such as remdesivir, in the country: “Use of these drugs is subjected to limited availability in the country as of now.”
IndiaSpend asked multiple executives at Roche and Cipla to explain the formal process for a patient to get tocilizumab in India, given the trouble people like Pinto and Dhawan faced in procuring the drug. A spokesperson for Roche Products, India, said patients can get it from Cipla who should be distributing this drug to hospitals, hospital pharmacies, government and individual patients with a valid prescription. IndiaSpend also sent queries on this to Cipla, but the company has not responded.
Pinto said he had tried to procure the drug through local Cipla executives whose numbers were listed on a helpline for Chennai. They were not able to get him tocilizumab, forcing him to drive to Hyderabad and back himself.
Roche also dismissed IndiaSpend’s direct query on the number of dosages it plans on importing into India in the next few months, with the spokesperson saying, “We have imported multiple shipments in the last few weeks.”
Can drug prices drop?
While tocilizumab presents a stark picture of the broken supply chain for drugs leading to inflated prices, it is a similar story in India for other drugs – for Covid-19 and otherwise – too.
Another investigational drug listed in the updated clinical management protocol is the antiviral remdesivir, made by the US pharmaceutical company Gilead Sciences, which the company has priced at $2,340, or Rs 1.77 lakh, per patient for a five-day course in developed countries.
There have been reports of difficulty in accessing this drug in India, too. However, many state governments, especially Tamil Nadu, have made efforts to procure it in recent weeks. Also, Gilead Sciences has licensed this drug out to a few Indian generic pharmaceutical companies such as Hetero Healthcare, which has announced that it would manufacture and sell it at Rs 5,400 per vial.
Another experimental drug, favipiravir, has been given manufacturing and sale approval by India’s drug controller for potential treatment of Covid-19. Each pill of this drug would be priced at Rs 103 and the entire treatment might cost Rs 12,566.
Seriously ill Covid-19 patients will often be given many of these drugs, either one after the other, or simultaneously, making the overall price of treatment hefty for many. Tocilizumab is given to patients in whom many of these other drugs have failed to stem the escalation of respiratory distress and when there are few options left. Patients and families are often in great anxiety by then.
A paper published in April 2020 in the Journal of Virus Eradication estimated that the highest list price for tocilizumab – for a 560-mg single dose – is $3,383 or Rs 255,849 in the United States and the lowest is $510 or Rs 38,570 in Pakistan.
The study analysed the cost of production for the most promising drugs under investigation for Covid-19, including tocilizumab, remdesivir, favipiravir and hydroxychloroquine. Many of these drugs being repurposed to fight Covid-19 “could be manufactured profitably at very low costs”, said the authors of the paper. These facts can strengthen price negotiations with the pharma companies and save a lot of money for governments around the world, they added.
But there are not many legal options available to the Indian government to regulate the prices of these experimental drugs during the pandemic. “The best option for the government is to undertake a bulk purchase agreement with Roche. This would allow them to negotiate prices, perhaps waive customs/import duties and drive the price down to the lowest level it could,” said Dinesh Thakur, a public health activist who has exposed malpractice in pharmaceutical companies.
It was not practical to expect other pharmaceutical companies to develop a biosimilar for tocilizumab that would be much cheaper and in such a short time, said Thakur. He also said that it was unlikely the Indian government would issue a compulsory license for tocilizumab that would allow a generic company to make a cheaper version of it.
“Now that the government has put this drug in the clinical management guidelines for off-label use, it should be available in Covid hospitals for those serious cases where it might be indicated. India’s Drug Price Control Order has powers to regulate the prices of drugs used in the treatment of Covid-19,” said Leena Menghaney from Médecins Sans Frontières’ Access Campaign.
The Drug Price Control Order affords the government some extraordinary powers to fix the prices of drugs in important or emergency situations. Most recently, this section was used by the government in 2017 to cap the prices of orthopaedic knee implants.
“If these powers are not used in this unprecedented public health emergency to prevent profiteering by pharmaceutical corporations, then the system is failing patients and the health system,” said Menghaney.
This article first appeared on IndiaSpend, a data-driven and public-interest journalism non-profit.