Regulatory Focus™ > News Articles > FDA Approves Modified Dosing Regimen for Bristol-Myers Squibb’s Cancer Treatment Opdivo

FDA Approves Modified Dosing Regimen for Bristol-Myers Squibb’s Cancer Treatment Opdivo

Posted 15 September 2016 | By Zachary Brennan 

FDA Approves Modified Dosing Regimen for Bristol-Myers Squibb’s Cancer Treatment Opdivo

The US Food and Drug Administration (FDA) has agreed to modify the dosage regimen for Bristol-Myers Squibb’s cancer treatment Opdivo (nivolumab) for the currently approved indications of renal cell carcinoma, metastatic melanoma and non-small cell lung cancer. 

The modification of the “Dosage and Administration” section of the label replaces “the single dose regimen of nivolumab (3 mg/kg intravenously every two weeks) with the new recommended regimen of 240 mg IV every two weeks until disease progression or intolerable toxicity for renal cell carcinoma, metastatic melanoma, and non-small cell lung cancer.” 

In addition, FDA said the nivolumab dosing regimen in combination with ipilimumab for melanoma will remain the same (nivolumab 1 mg/kg IV, followed by ipilimumab on the same day, every three weeks for four doses). However, after completion of ipilimumab, the recommended nivolumab dose will be 240 mg every two weeks until disease progression or intolerable toxicity, FDA added. The recommended dose for classical Hodgkin lymphoma remains 3 mg/kg IV, every 2 weeks until disease progression or intolerable toxicity, the agency said.

An FDA spokesman also told Focus: "One of the most compelling arguments to be made regarding flat dosing is the elimination of excess drug waste. Other considerations include convenience to health care providers and reduced concerns regarding accurate dosing in patients with weight fluctuations."

The agency based its approval on population pharmacokinetics analyses and dose/exposure-response analyses demonstrating the comparability of the pharmacokinetics exposure, safety and efficacy of the proposed new dosing regimen with the regimen that was previously approved.

“Based on simulations by the population pharmacokinetics model, FDA determined that the overall exposure at 240 mg every two weeks flat dose is similar (less than 6% difference) to 3 mg/kg every two weeks. These differences in exposure are not likely to have a clinically meaningful effect on safety and efficacy, since dose/exposure response relationships appear to be relatively flat in these three indications,” FDA added in a statement posted on Thursday.

Jaisy Wagner Styles, director of public affairs at Bristol-Myers Squibb, told Focus: "For the indications in non-small cell lung cancer (NSCLC), renal cell carcinoma (RCC) and unresectable or metastatic melanoma – this flat dose is intended to standardize dosing across all patients regardless of body weight and also to provide convenience to healthcare professionals in the preparation and administration of Opdivo (nivolumab). 

"There is a broad range of patient weights across advanced RCC previously treated with anti-angiogenic therapy, previously treated metastatic NSCLC, and unresectable or metastatic melanoma as a single agent patients. Some patients will receive a slightly higher dose, some will receive a lower dose, and for others the dose will not change," she added.

Opdivo sales in 2015 totaled almost $1 billion worldwide.

Modification of the Dosage Regimen for Nivolumab


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