Context: The Indian Patent Office has recently denied Johnson & Johnson’s (J&J) request to extend their patent on Bedaquiline, a tablet-form drug used for treating drug-resistant tuberculosis (TB), beyond July 2023. This decision paves the way for other drug manufacturers to produce generic versions of Bedaquiline, which is anticipated to be more economical and aid India in achieving its target of eradicating TB by 2025.
What is drug-resistant TB?
- Drug-resistant tuberculosis (TB) occurs when the bacteria causing TB become resistant to the medications used to treat it. There are different types of drug-resistant TB, including multi-drug-resistant (MDR) TB and extensively-drug-resistant (XDR) TB, which are much harder to treat than regular TB.
- MDR TB is resistant to at least two of the most commonly used drugs for TB treatment, while XDR TB is resistant to even more medications, making it much harder to treat. The incidence of drug-resistant TB is a major obstacle to eliminating TB in India and globally, and efforts are needed to strengthen TB prevention and control measures, increase awareness, and improve access to effective treatments.
- Drug-resistant tuberculosis (TB) is a serious global health challenge that occurs when the bacteria causing TB become resistant to the medications used to treat it.
- India has a high burden of drug-resistant TB, including MDR TB and XDR TB. According to the World Health Organization (WHO), India accounted for around a quarter of the world’s cases of MDR TB and XDR TB in 2019.
How is drug-resistant TB treated?
- Drug-resistant TB is a form of TB caused by bacteria that have become resistant to the medications used to treat it. Treatment for drug-resistant TB is more complex and longer than for regular TB.
- TB is typically treated by following a strict schedule of drug doses and frequencies prescribed by a physician. Failure to adhere to this schedule can lead to drug-resistant TB. However, deviations from the schedule can occur due to drug side effects that decrease quality of life or inadequate access to necessary drugs.
- One of the primary drugs used to treat pulmonary MDR TB is Bedaquiline. In 2018, the World Health Organization recommended an oral regimen that included Bedaquiline, replacing two injectable drugs for MDR TB.
- Although Bedaquiline had not completed phase III trials, the recommendation was based on smaller trials, outcomes in TB elimination programs, and the difficulty of treating MDR TB. Patients receiving the drug were closely monitored.
How effective is Bedaquiline in treating drug-resistant TB?
- Bedaquiline is typically prescribed for a period of six months, with a higher dose in the first two weeks followed by a lower dosage for 22 weeks. This is shorter than the treatment routines for pulmonary MDR TB, which can last between 9 to 24 months.
- Results from a phase II clinical trial showed that Bedaquiline was effective in converting a patient’s sputum culture from positive to negative, with durable results observed at 24 weeks and a high likelihood of response at 120 weeks.
- Compared to other second-line treatment options that are injected and can have severe side effects like permanent hearing loss, Bedaquiline is available in tablet form and is less harmful. However, it has potential side effects of its own, such as toxicity to the heart and liver. As such, it is recommended only when other treatment options for MDR TB have failed.
- In India, Bedaquiline use is governed by guidelines under the Programmatic Management of MDR TB as part of the National TB Elimination Program.
- However, the WHO’s decision to recommend Bedaquiline before it completed its phase III trials raised ethical questions about the safety threshold for pharmaceutical companies producing drugs for desperate patients and the use of insufficiently tested drugs on compassionate grounds.
Why was the patent application for Bedaquiline production rejected?
- Johnson & Johnson (J&J) filed a patent application for the production of a fumarate salt compound to create Bedaquiline tablets, but it was opposed by two groups:
- 1) Network of Maharashtra people living with HIV and
- 2) TB survivors Nandita Venkatesan and Phumeza Tisile, supported by Médecins Sans Frontières.
- The groups argued that J&J’s method to produce a “solid pharmaceutical composition” of Bedaquiline was obvious and didn’t require an inventive step. The Indian Patent Act 1970 requires an invention to be “not obvious to a person skilled in the art” to be granted a patent.
- In addition, they claimed that J&J’s application lacked information about foreign patent applications, their specifications, and priority dates, among other details required under Section 8 of the Act.
- They also argued that the current application drew heavily from a previous patent, WO 2004/011436, which discussed a similar compound on which Bedaquiline is based, and whose priority date (2002) preceded the new application.
- The Patent Office rejected the application on several grounds, including Sections 3d and 3e of the Act, which state that a “new form of a known substance which does not result in the enhancement of the known efficacy of that substance” and “a substance obtained by a mere admixture resulting only in the aggregation of the properties of the components thereof” are not patentable.”
Why is the rejection notable?
The rejection of J&J’s patent application for the production of the fumarate salt of Bedaquiline tablets is notable for several reasons. India has the world’s largest population of people living with drug-resistant TB, and J&J’s patent enabled them to charge $400 (Rs 33,000) for the six-month treatment, in addition to the cost of other drugs. With the rejection of the patent, the cost of Bedaquiline is expected to drop by up to 80%.
The Indian government has directly procured and distributed the drug through state-level TB programs, and since 2016, India has also received free donations of Bedaquiline from J&J and the US Agency for International Development.
The rejection of the patent application is also significant as it addresses the issue of ‘evergreening,’ where patent owners continuously extend their rights and apply multiple patents for the same product.
The rejection of the patent application was due to various grounds, including the fact that J&J’s method for producing the solid pharmaceutical composition of Bedaquiline was deemed “obvious” and did not require an “inventive step.”
In addition, the application did not provide the necessary information about foreign patent applications and their specifications, and it was found to be significantly based on a previous patent, WO 2004/011436. Furthermore, the application violated Indian law, which disallows “evergreening.” J&J’s current patent is set to expire in July 2023.