Mylan and Biocon Get a Second CRL for Insulin Glargine Follow-on

Over the weekend, drug maker Biocon disclosed that it and partner Mylan have been issued a second Complete Response Letter (CRL) for their follow-on insulin glargine product referencing Lantus.

According to Mayank Verma, the company’s secretary and compliance officer, in an August 31 letter to the National Stock Exchange of India, “The CRL has been issued pending completion of the Corrective And Preventive Actions…submitted to the US FDA in response to the observations made at the conclusion of the pre-approval inspection of our insulin manufacturing facility in Malaysia in June 2019.”

Verma added that the CRL did not note “outstanding scientific issues” with the application, and said that the CRL was not anticipated to have an impact on the company’s planned launch timeline.

This new regulatory challenge comes just weeks after Biocon announced that it had gained a certificate of good manufacturing practice from the European Medicines Agency’s Irish inspection authority for the Malaysian manufacturing site.

The setback also follows a previous CRL, in June 2018, for the follow-on insulin. In 2018, a Mylan representative told The Center for Biosimilars^® that, “Following submission of our Insulin Glargine application under the 505(b)(2) regulatory pathway, we had agreed with FDA to provide additional clinical data in support of the manufacturing site change from Bangalore to Malaysia. Hence, the recent CRL was anticipated and built into our plan."

Prior to the initial CRL, the company received a Form 483 from the FDA, inclusive of 6 observations, after an inspection of the Malaysia facility. Another inspection of the site in June and July 2019 yielded another Form 483 with 12 observations.

The follow-on product is already authorized in the European and Australian markets, where the product is regulated as a biosimilar and is sold under the brand name Semglee.

The product was authorized in these territories on the basis of data that included those from the phase 3 INSTRIDE 1 study in 558 patients with type 1 diabetes.¹ The follow-on insulin was shown to be noninferior to its reference product in terms of change in glycated hemoglobin when administered once daily with mealtime insulin lispro. The follow-on was also shown to be well tolerated, and no new or significant safety issues were observed during the study.

Reference

Blevins TC, Barve A, Sun B, Ankersen M. Efficacy and safety of MYL-1501D vs insulin glargine in patients with type 1 diabetes after 52 weeks: results of the INSTRIDE 1 phase 3 study [published online April 15, 2018]. Diabetes Obes Metab. doi: 10.1111/dom.13322.