(MENAFN- Live Mint)

New Delhi: India's top drug regulator has denied approval for Serum Institute of India Pvt. Ltd.'s new tuberculosis vaccine, calling the test data“not adequate and conclusive", according to a document and two government officials familiar with the matter.

The Special Subject Expert Committee (SEC) on Vaccines at the Drugs Controller General of India (DCGI) last month found that the main studies failed to clearly demonstrate that the recombinant BCG (rBCG -VPM1002) was effective, according to the minutes of the meeting reviewed by Mint.

A recombinant BCG vaccine is a genetically modified version of the traditional TB vaccine that is based on a weakened strain of Mycobacterium bovis.

The regulator found the Serum Institute of India's (SII's) specialized, later-stage analysis to be unreliable, asking the company to conduct a new, larger study to get clear and convincing proof that the vaccine works before seeking approval for public use.

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Tuberculosis (TB), mainly caused by Mycobacterium tuberculosis in humans, is the biggest killer among communicable diseases in India, with about 2.6 million new cases and 321,095 deaths reported in 2024, according to the Union health ministry's India TB report. While the country targets to eliminate the disease by the end of this year, five years ahead of the United Nations' Sustainable Development Goals (SDG) deadline of 2030, the task has become challenging in the absence of a protective TB vaccine.

“A crucial need exists for a new and effective TB vaccine, as the standard BCG vaccine's efficacy is limited beyond early childhood," said Dr. Soumya Swaminathan, principal advisor for the National TB Elimination Programme.“Definitely, the TB control programme will get a big boost if we have an effective and safe vaccine."

Queries emailed to the spokespersons of the Union health and family welfare ministry, DCGI, and Serum Institute on Friday remained unanswered.

Serum's vaccine

SII had first applied to the DCGI for emergency use authorization for this vaccine in March 2022. SII's vaccine was designed to provide better protection against pulmonary and extrapulmonary TB in individuals aged six and above, a group where the current BCG vaccine has shown inconsistent efficacy.

SII had submitted two studies for approval, according to the minutes of the committee meeting held on 15 October.

“The committee deliberated the proposal extensively and recommended that the study data with post hoc analysis was not adequate and conclusive to take a considered decision for the new drug application. The firm should plan adequately powered study based on the outcome of secondary endpoint of ICMR study for conclusive decision," read the minutes.

The committee felt that the data was inadequate and lacked efficacy, said the first government official cited above, who spoke on the condition of anonymity about the regulatory process.

There are other TB vaccines under development globally, including the M72 vaccine (supported by the Gates Foundation), as well as mRNA vaccines from Gennova and BionTech and MTBVac from Biovac group.

“While the (Serum Institute's) study's primary outcome showed no significant difference, a subgroup analysis indicated a positive trend in children aged 6-14 years, with recombinant BCG suggesting lower incidence of both pulmonary and extrapulmonary TB compared to the placebo," said Swaminathan, who was earlier the World Health Organization's chief scientist.“These findings were based on a small sample size and require confirmation through larger trials."

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In Study 1, which focused on preventing recurrence of the disease in successfully treated pulmonary TB patients, the vaccine failed to meet its primary endpoint, according to the committee. The subsequent analysis (post-hoc) showed the efficacy difference between the vaccine and placebo groups for all recurrence cases was not statistically significant, the committee said, noting that this analysis was unrelated to the present application

Study 1 found that the Serum Institute's vaccine reduced TB recurrence in bacteriologically confirmed and clinically diagnosed cases by 13.5%, and by 7.8% in bacteriologically or diagnostically confirmed infections alone.

In a large phase III trial conducted under Study 2 by the Indian Council of Medical Research (ICMR) on healthy household contacts of sputum-positive TB patients, the vaccine did not meet its primary objective of evaluating efficacy over a three-year period. This trial tested Serum Institute's rBCG vaccine as one of the three arms against a placebo. The overall vaccine efficacy against all microbiologically confirmed TB (pulmonary and extrapulmonary) was found to be 16.9%, which the committee deemed statistically nonsignificant.

“The statistically nonsignificant result was interpreted and concluded as statistically significant based on the calculation of the two-arm data instead of three arm data of the ICMR study," the minutes of the meeting said, adding,“The primary objective of the study was not met and firm has not drawn any inference from the same."

The second government official cited above, also speaking on the condition of anonymity, said,“The rejection rate varies widely on the complexity of the vaccine, the trial phase and the standard of data presented. Typically, the large-scale confirmatory trials take several years to complete."

According to Swaminathan, also the former director-general of ICMR, the recombinant BCG vaccine holds the key advantage of a positive safety profile.“However, definitive efficacy necessitates larger studies as mandated by the DCGI to ensure the vaccine's safety and effectiveness before public use."

Drug-resistant TB threat

TB in India accounts for an estimated 26% of the global TB burden and contributes to drug-resistant infections.

“Given that TB is an infectious disease, a preventive vaccine is crucial because if a person is sick, there's a high chance those in close contact with them will also catch the infection and develop active TB," said Dr. Randeep Guleria, former Director of the All India Institute of Medical Sciences-Delhi and India's former Covid Czar.

“Current TB treatment is long, and even though it's been shortened to a few months, patients often stop taking their medication, which can lead to the development of multi-drug-resistant TB (MDR-TB)," said Guleria, currently a pulmonologist at Gurgaon-based Medanta Hospital.

According to the India TB report, the national TB elimination programme diagnosed 63,939 cases of MDR-TB and 114 extensively drug-resistant (XDR-TB) cases in 2024.

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“We already use the BCG vaccine in children, but it offers only very mild protection. ICMR is conducting further trials on adults who are at high risk of developing active TB. The Serum Institute's data did not show statistically significant efficacy, which is why the committee did not approve it," Guleria said.

According to Dr Rajeev Jayadeven, a public health expert,“Despite extensive screening, testing, and treatment, TB remains a formidable enemy.“...If a truly effective vaccine becomes available, it will be a major breakthrough. Unfortunately, the new recombinant BCG vaccine showed only 16.9% overall effectiveness in the recent trial, which is not optimal for widespread use."

While the subsequent analysis indicated 50.4% effectiveness against extrapulmonary TB–which infects organs other than lungs–the regulator rightly called for larger studies, he said.“With rising drug-resistant TB, multipronged efforts need to continue."

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