A subject expert committee (SEC), which advises the Indian regulator on trial-related permissions, has recommended that Novartis AG’s cyclin-dependent kinase 4/6 inhibitor, Kisqali (ribociclib), be cleared for marketing in India.
Novartis had sought a waiver of local clinical trials for the product in India and the SEC (oncology and hematology) at its meeting last month noted that ribociclib addresses an “unmet medical need”. It is indicated in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced or metastatic breast cancer.
The SEC recommended that permission be granted to import and market the drug subject to the condition that Novartis submits the report of ongoing global clinical trials where India is one of the participating countries, details of the SEC meeting held on May 16 indicated.
Asked how many Indian women are part of the pivotal Phase III MONALEESA-2 trial for ribociclib, Novartis told Pink Sheet that India is participating in MONALEESA and ribociclib studies “with adequate number of patients” to study safety and efficacy of the molecule for advanced breast cancer patients.
The US FDA had, in March this year, approved ribociclib based on the superior efficacy and demonstrated safety of the drug plus letrozole versus letrozole alone in the pivotal Phase III MONALEESA-2 trial. (Also see "FDA's NDA And BLA Approvals: Imfinzi, Steritalc, Kisqali Femara Co-Pack" - Pink Sheet, 7 May, 2017.)
Indian Review Process Tweaked
The SEC go-ahead for ribociclib is significant given that in early June, India stipulated pivotal tweaks to its existing three-tier review process for clinical trial-related clearances.
Under the new approach, in general, once global clinical trial (GCT) proposals are accepted or rejected by the SEC, no further approval of the Technical Committee or Apex Committee will be required, though there are riders applicable in certain circumstances. The existing three-layered system required recommendations of the SECs to be vetted by the Technical Review Committee and then cleared by the Apex Committee.
It is not immediately clear whether Kisqali will need any further regulatory clearances in India or then can gear for launch. Novartis appeared non-committal and maintained that the SEC serves as an advisory committee to the health authorities.
“It is the prerogative of the health authorities whether or not to follow recommendations of the SEC,” it said.
Filing Through Sandoz
Interestingly, the filing for Kisqali in India has been routed through Sandoz Private Ltd, a 100% arm of the Swiss parent, rather than Novartis India Ltd, the listed entity with a public shareholding, raising concerns among some analysts on the group’s approach for important new product introductions in the country.
Some analysts say that such strategies could hurt the interest of minority shareholders in the listed entity in India given the earnings potential of such products, and also raises some questions on oncology product flows against the backdrop of the 2014 global transaction between Novartis and GlaxoSmithKline PLC. (Also see "Novartis in $28.5bn+ mega-deal with GSK, Lilly" - Pink Sheet, 22 Apr, 2014.)
“Launch plans through 100% arms seem to be gaining some traction again – we saw that with Sanofi as well over the recent past,” one analyst told Pink Sheet.
Sanofi, he noted, had last year expanded its diabetes portfolio in India but launched the products Lyxumia (lixisenatide) and Zemiglo (gemigliptin) through Sanofi-Synthelabo (India) Private Limited, rather than the listed entity, Sanofi India Ltd.
Sanofi at the time apparently explained that products sold in India by Sanofi subsidiaries are based on research done by the parent company or licensed by it from other companies. “Brand names are also owned by Sanofi. Hence, all launches are decided in consultation with the parent company,” Sanofi said at the time.
An industry veteran told Pink Sheet that launching a new patented oncology product through a wholly owned arm goes against the interest of the listed entity's shareholders in the Indian market, given that new products drive growth and oncology drugs, in particular, improve profitability, he noted.
But he also referred to the complex dynamics at play with pricing pressures in markets like the US, which could make it tough for innovator firms to launch such products at “significantly differentiated prices”. Then, there is also the “fear” of health activists and government interventions.
“I am not sure either of these issues will be resolved by launching through a generic subsidiary. Instead, it may aggravate the difficult situation by displeasing minority shareholders,” the veteran added.
Asked about the Kisqali filing, Novartis told Pink Sheet that Sandoz is a Novartis group company and that it had been “an internal decision” to file ribociclib through Sandoz Pvt. Ltd.
On analysts concerns about routing Kisqali through the 100% arm, the Swiss multinational said: “Novartis operates through multiple entities in India. A decision to launch a product through a particular entity is based on numerous factors including therapeutic area, reach, field force capability, investments required among others.”
Novartis also said that the transition of the oncology portfolio acquired from GSK had been completed successfully and the drugs are available across the country. “Performance of the acquired brands have been in line with expectations,” it noted.
The 2014 global deal included Novartis snapping up GSK’s oncology products and Novartis divesting its vaccines business to GSK, besides other transactions. At the time of the transaction, of the oncology products acquired by Novartis, only four - Tykerb (lapatinib), Revolade(eltrombopag), Votrient (pazopanib) and Hycamtin (topotecan) - were apparently sold in India