The Bedaquiline conundrum: Why this TB drug is creating an intense debate

No other drug in recent times created as much buzz as Bedaquiline.

Bedaquiline, developed by Johnson & Johnson (J&J), is used for the treatment of pulmonary multidrug-resistant tuberculosis (MDR-TB).

MDR-TB refers to TB resistant to at least two of the first-line or most commonly used drugs: Isoniazid and Rifampicin. Among MDR-TB, the more dangerous strain is the extensively drug resistant TB (XDR-TB), which has additional resistance to at least one Fluoroquinolone and one second line injectable drug.

It is estimated that 147,000 people in India have MDR-TB, accounting for one-fourth of global burden, as per Global Tuberculosis Report 2017. Around 6.19 percent of all TB patients in India have MDR-TB. Among MDR-TB patients, the XDR-TB rate was 1.3 percent. There is clearly an unmet need and patients are dying.Bedaquiline promise

Bedaquiline was the first targeted TB medicine with a novel mechanism of action in more than 40 years.  The drug came as saviour to patients for whom all other medicines had failed.

Given the unmet need and the promising data on efficacy of the drug in phase two clinical trials, US Food & Drug Administration granted fast-track designation, priority review and orphan-product designation to Bedaquiline.

In 2012, it conditionally approved the drug, awaiting the larger phase three clinical trial data and asking the company to carry a black box warning for patients and healthcare professionals about the risks.

Today, it is approved in more than 56 countries, including those with the highest TB burdens.

The drug is now included on the World Health Organisation’s (WHO) Essential Medicines List. WHO last year recommended Bedaquiline as the frontline medicine for treatment of all MDR-TB cases revising its earlier recommendation for patients with XDR cases. Bedaquiline is also poised to replace the current daily injections to treat MDR-TB that can have serious adverse effects leading to many patients discontinuing their treatment midway.

What’s the debate about?

Janssen’s tier-pricing for the drug is pegged at $30,000 for a six-month course in high-income countries, $3,000 for middle-income and $900 for low-income regions.

India is one of the few countries where J&J offers the drug free of cost under a conditional access programme, which will end in March. J&J is currently offering 10,000 courses of the drug for a duration of six months.

India currently administers the drug through a highly controlled, government monitored programme. The Revised National Tuberculosis Programme (RNTCP) has been distributing the drug only in a few designated government centres.

While thousands of people are succumbing to XDR-TB, only few among them are receiving treatment. So, there is a pressure on India to follow South Africa and Russia to expand Bedaquiline access to all MDR-TB patients.

Ethical questions

There are ethical questions despite ever growing medical confidence about the drug.

A section of legal and health experts have raised the issue of discrepancies in the informed consent forms and granting go ahead for the drug without the much larger phase three clinical trial data, which establishes safety and efficacy of the drug.

They point to the drug’s potential risks, including increased risk of death. About 11.4 percent of patients taking Bedaquiline died during phase two clinical trials compared with 2.5 percent of those taking placebos.

“The concern raised by several stakeholders in the industry, on the clause forcing patients to waive any right to compensation, in case if anything went wrong and the complete silence on their data transferred to Janssen, the company that made the drug in actual may not be founded, as the consent form discloses that there may be known and unknown side effects and the information will be shared with relevant authorities,” said Arun Kumar G, Partner and A Yamuna, Senior Associate at K&S Partners to Moneycontrol.

They also said that as per the criteria the patients are managed indoor for a period of 2 weeks and managed by the respective centers.

“The current debate projects a need for government intervention on availability of the drug to all patients and ignores the core issue that the regulatory approval is for conditional access of the drug and that too in six centres located across India identified by the government. There is a third dimension of informed consent (on the part of the patient) that the recent conversations have completely overlooked,” Kumar and Yamuna added.