This post has been updated with additional information on the court ruling.
A teenager who sued the Indian government to gain access to a new drug against multidrug-resistant tuberculosis was granted her petition in a ruling handed down by the New Delhi High Court on January 18, according to the family lawyer. The decision was widely reported in the Indian press.
That drug, bedaquiline, has been approved for use only in a handful of Indian cities and only for the small subset of patients who can demonstrate laboratory evidence of extensively drug resistant TB, or XDR-TB.
"It's the first time anyone, that we know of, has sued the government for access to new TB drugs," said Jennifer Furin, an infectious disease doctor at Harvard University. She submitted an expert opinion to the court on behalf of the patient and her father, Kishore Tripathi.
The ruling has hastened the Indian government's rollout of bedaquiline. In a court hearing on January 20, representatives for the government said that the Revised National Tuberculosis Control Program (RNTCP) in India would make bedaquiline available in 70 more centers nationally by mid-2017, according to the legal team representing the family.
A representative from India's Revised National Tuberculosis Control Program declined to comment for this story.
The teen was diagnosed with TB in 2013. Other TB drugs failed to slow the course of her illness. Last year, her family traveled 660 miles from Patna in Bihar state to try and get bedaquiline through the National Institute of Tuberculosis & Respiratory Diseases in New Delhi, also known as the Lala Ram Swarup TB Hospital. But the government facility denied her access to the drug initially because she was not a New Delhi resident. Additionally, they said she did not meet the eligibility requirements because she did not have a positive result for drug-resistant TB.
The family sued on the grounds that she has a right to life-saving medical treatment, claiming that her medical history indicated a likely XDR-TB infection. The hospital, at the January 20 hearing, said that it would no longer require New Delhi residence for bedaquiline eligibility. This will probably lead other government facilities to drop the residence requirement for bedaquiline as well.
The ruling also requires the national drug regulatory agency to process the patient's application for another advanced TB drug, delamanid, in the next 24 hours. The drug is not licensed in India but is available from the Japanese manufacturer, Otsuka by way of a compassionate use program — meant to provide pre-approval drugs to patients with serious health problems.
"For years we begged for new things to do a better job for our patients, and when we have them, there's this incredible delay getting them out to people who need them most," Furin said. Based on numbers from the latest World Health Organization TB report, she estimates that 30,000 patients in India might benefit from bedaquiline, but as of December 2016, only 164 have been given the drug. The drug has been licensed in India since April 2016.
Meanwhile, the 18-year-old patient's weight has dwindled to 55 pounds.
The family moved to Mumbai in the days before the ruling in pursuit of treatment for the teen. Because she is too ill to move back to Delhi and because the teen's drug regimen will eventually include delamanid, which government facilities don't have access to, the patient's doctor will be able to procure and treat her with bedaquiline as well. Most TB patients receiving bedaquiline are required to be treated at government-run facilities.
But TB specialists are far from reaching a consensus on the safety and success rate of bedaquiline.
The drug is manufactured by the Johnson & Johnson subsidiary, Janssen Pharmaceuticals, under the trade name, Sirturo. In preliminary clinical trials, it was effective at clearing TB bacteria from sputum samples, a proxy for recovery from TB infection. But there were concerns about high rates of heart problems and more deaths (from various causes) among those treated with the drug than in the control group that did not receive the drug. That troubled TB researchers and clinicians. Since the drug's approval, those problems have not been widely seen in patients taking bedaquiline.
"Normally we would not even have talked about licensing a drug like that but there was such a desperate need for treating MDR [multiple drug-resistant] and XDR patients," said Clifton Barry, chief of the Tuberculosis Research Section at the National Institute of Allergy and Infectious Disease. "That's the tension that's spilling over into the Indian situation. The scientific evidence is not perfect, but the need is so great."
Since its introduction, the drug has helped TB cases that seemed hopeless and side effects have not been a major problem so far, as TB specialists initially feared. Furin said that of the nearly 6,000 patients who have received bedaquiline so far, there is an approximate 80 percent cure rate. But that group, Barry pointed out, is highly vetted and followed carefully by doctors. The population who would be included in a rigorous and large-scale clinical trial of the drug would be markedly different. But the only trial of that kind just started enrolling participants in 2016, so no data is available yet.
"You can get fooled by statistical flukes in a Phase 2 [trial] which is relatively small, which is all that they've done so far," said Barry. Larger Phase 3 trials would confirm or refute the risks found in earlier Phase 2 trials, which are usually done in smaller populations. The lack of side effects in patients who have received bedaquiline since the FDA approved the drug in 2012 is reassuring, he said, adding that a rigorous large-scale clinical trial would be more likely to uncover any potential problems with the drug.
Public health officials in each country using bedaquiline strictly regulate the drug and carefully monitor patients, not just because of fears about drug toxicity but because of the specter of bedaquiline resistance. Indiscriminate use of older TB drugs is partially responsible for TB drug resistance. The approach India and a few other countries such as Mexico and Brazil have taken has been conservative, but Barry believes "the caution is advisable."
"It's heartbreaking to read cases like that," Barry said. "If that was my daughter, I'd absolutely want her to get bedaquiline, no questions about it. But, you know, if I put my scientist, clinical trials, drug developer hat on, I'd say, [rollout] needs to be done carefully before being done widely."
This case highlights the tightrope that public health officials must walk. Maintaining the integrity of a national TB program requires painful choices that may include turning away dying patients who come knocking at the door.
As a result of the ruling, the Indian government will now open the door to those patients.