BioDelivery Sciences International received FDA approval of its 505(b)(2) NDA for buccal fentanyl on July 16, 2009. Most notable about this approval is the first REMS (Risk Evaluation and Mitigation Strategies). The FDA cautioned that this REMS shouldn’t be used as an example for other opioid products. The reason is that the product is indicated for “the management of breakthrough pain in cancer patients who are already receiving and who are tolerant to opioid therapy for their underlying persistent cancer pain” (emphasis added). Thus, the risks are much less of existing patients than for treatment naive patients. Even so, the REMS plan is extensive.
The buccal fentanyl product received approval based on pk and two Phase III studies. From BDSI’s website we see the summary of the 2 Phase III studies (BEMA was the former trade name, now ONSOLIS (TM)):
“Patients on stable background opioid medication were enrolled in an efficacy study, and 81 received BEMATMFentanyl and placebo in a randomized multiple crossover design for their breakthrough cancer pain episodes. A total of 394 BTP episodes were treated with BEMATMFentanyl and 197 with placebo. Lack of effective pain relief leading to withdrawal during the initial open label titration phase was infrequent (3.3% of patients). In the double blind portion of the study, sum of pain intensity differences were significant in favor of BEMATMFentanyl at all time points from 15 minutes through 60 minutes, the last assessment time. In the safety study, more than 56,000 BTP episodes in 220 patients were treated with BEMATMFentanyl. Study medication performance was rated as ‘good’, ‘very good’ or ‘excellent’ in 85% of all BTP episodes treated. The safety profile was consistent with opioid use. BEMATMFentanyl was associated with a low incidence of application site reactions, with 1.3% considered probably or possibly related to the drug. Most cases were mild and none led to discontinuation.”
For their efforts, BDSI will be getting a princely sum of money. BDSI had licensed the product to Meda for milestone and royalty payments. On 7/22, BDSI announced it had received a $26.7 million milestone payment and would be entitled to double-digit royalty payments plus $30 million upon achievement of sales objectives.