Roche’s Immuno-Oncology Therapy On Course To Indian Debut?

Roche’s cancer immunotherapy Tecentriq has received conditional marketing authorization under India’s layered approval process, setting the stage for a potential debut in the country. However, it remains to be seen how India’s evolving regulations in the area of clinical trial waivers could play out for such products.

A subject expert committee (SEC), which advises India’s drug regulator on trial-related permissions as part of a layered approval process, has recommended conditional marketing authorization for Roche’s anti-PD-L1 cancer immunotherapy Tecentriq (atezolizumab).

The SEC approval permits a clinical trial waiver “at this stage” for the product in view of it fulfilling “unmet need” and being for “serious/life threatening” disease, and since there is no alternate therapy for metastatic urothelial carcinoma.

“The drug has shown unprecedented safety and efficacy; the firm has ensured that the global clinical trial (Phase III) in three indications including metastatic urothelial carcinoma would be conducted in India,” details culled from recommendations of an SEC (oncology and hematology) meeting on Jan. 12 state.

India currently follows a three-tier review process for clinical trials, under which applications are initially evaluated by specialized SECs. The recommendations of the SECs are then generally vetted by a technical review committee and finally cleared by an "apex committee".

Benefit-Risk Decisions

The SEC suggested that an approval for Tecentriq may be considered, subject to Roche submitting postmarketing surveillance data of the drug in the “said indication” in the Indian population. However, it specifies that the firm will need to submit the Phase III global clinical trial protocol and start enrolling subjects before marketing the drug in the country.

Asked whether enrolment of Indian subjects for the Phase III study in India had commenced and the proposed enrolment numbers, Roche told Pink Sheet that it is awaiting the formal approval from the regulatory authorities, including the clinical trial waiver, and would not be able to comment at this time.

“Roche respects and supports the role of regulatory authorities in making the benefit-risk decisions that determine access to new products and will abide by the directions of the regulatory authorities,” the Swiss multinational stressed.

Phase II data “generated in the US” has been presented to the Indian regulator, the SEC meeting observed.

In May 2016, the US FDA granted Tecentriq accelerated approval for people with a specific type of advanced bladder cancer. In January, this year, the product received priority review in an additional type of advanced bladder cancer; the US agency is expected to make a decision on this approval by April 30.

Other immune checkpoint inhibitors such as Merck & Co. Inc.’s Keytruda (pembrolizumab) and Bristol-Myers Squibb Co.’s Opdivo (nivolumab) have also made regulatory headway in India. Last year, Keytruda was reported to have received regulatory approval in the country, while the SEC had recommended marketing authorization for Opdivo. (Also see "BMS' Opdivo Heading Towards Indian Debut?" - Scrip, 7 Apr, 2016.)

Trial Waivers

It will be interesting to see how the trial waiver exemption is applied in the case of Tecentriq, given certain recent tweaks proposed around the clause including allowing such exemption for drugs already approved in ICH (International Conference on Harmonization) countries, subject to specific conditions. Some of the new proposals are not yet part of the legal framework, though.

Last month, India’s Drugs Technical Advisory Board (DTAB), which is the highest technical body under the national Drugs and Cosmetics Act, proposed that a waiver of clinical trials for medicines already approved in ICH countries be considered subject to specific conditions, including an inspection by India’s Central Drugs Standard Control Organization (CDSCO) of R&D facilities for “batches manufactured for regulatory approval” of the drug.

“It may also be ensured that the drug [for which a waiver is being sought] is being marketed in the country of origin,” the DTAB said, as per details in the minutes of its 75th meeting held on Jan. 3, 2017.

Waiver Procedures

Then on Jan. 17, the CDSCO - referencing a Nov. 2016 decision of the apex committee - said that in future, cases of waivers need not be taken to the technical/apex committees and should be “considered and disposed of” by the central licensing authority as per the regulations. The technical committee will act as an appellate committee in cases of disputes, the CDSCO stated.

Asked whether the new requirements, including an inspection of R&D facilities, would perhaps apply to the Tecentriq trial waiver, Roche reiterated its position on the role of regulatory authorities in making the benefit-risk decisions, but declined further comment since “these decisions are under the purview of the regulators”. (Also see "India’s Trial Approval Timelines Report Card – Some Red Lines?" - Pink Sheet, 16 Jan, 2017.)

Some industry experts had previously questioned the additional value that the inspection of innovator R&D sites would bring under the proposed new trial waiver clause, given that most of the data would have probably been vetted by reputable regulators; such plans could also require a more coordinated effort with foreign regulators.

Currently, a waiver of clinical trials in the Indian population for new drugs, which have already been approved outside India, is permitted only in cases of "national emergency, extreme urgency, epidemics and for orphan drugs for rare diseases and drugs indicated for conditions/diseases for which there is no therapy."

From the editors of PharmAsia News.