CDSCO Committee turns down Novartis FDC drug including Vildagliptin, Metformin, Glimepiride

New Delhi: The Swiss drugmaker, Novartis recently presented before the Central Drugs Standard Control Organization(CDSCO) Technical Committee to seek approval manufacture and market its Fixed-Dose Combination of Vildagliptin 50mg + Metformin 850mg + Glimepiride 2.mg Tablets. However, the committee rejected to grant permission for the same while agreeing with the recommendations of the Subject Expert Committee (Endocrinology & Metabolism).

The proposed FDC drug is indicated for an adjunct to diet and exercise in patients inadequately controlled with the Metformin and sulfonylurea.

Initially firm's proposal was taken up by the SEC wherein the committee opined that there is no rationality in combining two insulin secretagogues in one FDC. Moreover, the committee also noted that the clinical study data presented by the firm is not on the proposed FDC. Further, the firm informed the committee that proposed FDC is not marketed anywhere in the world. Hence, the committee did not recommend for the proposed FDC.

After three months, the firm's proposal was once again deliberated by the SEC Committee following the company's response.

The CDSCO committee opined that although SU & DPP-IV inhibitors act differently, the outcome of both the drugs is to stimulate insulin secretion. The justification that this FDC will be useful for patients who require 3 drugs as add-on therapy and hence FDC of the 3 drugs will be useful was not justified with adequate data. The clinical trial data presented is on the 3 drugs given as add-on therapy and not with the proposed FDC. The committee also noted that the proposed FDC is not approved in any country. In view of the above, committee after detailed deliberation reiterated its earlier stand and didn't recommend approval of the proposed FDC.

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Justification submitted by the firm:-

• In fact, as per lQVlA September 2018 data, as many as 16% prescriptions of OADs comprise of triple drugs. The report also suggests that 40% co-prescriptions of Galvus (Vildagliptin) are with a SU + Metformin and 22% co-prescriptions of GalvusMet (Vildagliptin + Metformin) are with a SU. This data is indicative and conclusive of the fact that 50% of patients are presently already on a Vildagliptin (DPP-4 inhibitor) + Metformin + SU.

• The guidelines recommend adding a DPP-4 inhibitor to Metfoi min and SU or, a SU to Metformin + DPP4 inhibitor combination in case of inadequate glycemic control while on either of the combinations and it is evident from lQVlA data that a significant number of prescriptions are of triple drugs.

• The proposed FDC will ensure improved adherence for achievements of long-term treatment goals. Polypharmacy with increased pill burden and dosing frequency are identified as factors responsible for poor adherence to oral hypoglycemic therapy. In a study of 2741 patients on an oral antidiabetic drug (OAD), there was an inverse relationship between OAD adherence and HbA1c; controlling for baseline HbA1c and therapy regimen, each 10% in oral diabetes medication adherence was associated with a 0.1% HbA1c decrease (=°0.0004), suggesting that adherent patients are more likely to achieve glycemic control than the nonadherent ones.

The firm presented their proposal before the CDSCO Technical committee which after detailed deliberation, agreed with the recommendation of the Subject Expert Committee (Endocrinology & Metabolism) and did not recommend for approval of the proposed FDC.

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