Pacira Pharmaceuticals, Inc.

Pictured: FDA Headquarters/iStock, JHVEPhoto The FDA has a busy schedule leading up to Thanksgiving, with three target action dates and an advisory committee meeting to discuss delayed confirmatory trials for two investigational cancer assets. Pacira Pushes to Expand Anesthetic’s Label The first FDA verdict this week is expected for Pacira BioSciences, which is proposing to expand the label of its anesthetic Exparel (bupivacaine liposome injectable suspension) to include both single-dose use for sciatic nerve block in the popliteal fossa and to block the femoral nerve in the adductor canal. The regulator has a deadline of Nov. 13. Exparel uses multivesicular liposomes to deliver bupivacaine, a potent local anesthetic. This combination allows Exparel to gradually release bupivacaine over time, leading to strong and durable reduction in pain scores and a notable decrease in the need for opioid medication. Currently, Exparel is only approved as a single-dose infiltration to induce postsurgical local anesthesia in patients 6 years and above and as an interscalene brachial plexus nerve block for postsurgical regional anesthesia in adults. Since its initial approval in 2011, Exparel has been administered to over 12 million patients in the U.S., according to its maker. To support the label expansion, Pacira’s supplemental New Drug Application (sNDA) included data from two Phase III studies, which together showed “statistically significant and clinically meaningful” reductions in postsurgical pain through 96 hours compared with bupivacaine HCl in patients who had undergone surgeries in their lower extremities. Exparel also resulted in lower opioid consumption and demonstrated a favorable tolerability and safety profile. CorMedix Hopes for Light at the End of Regulatory Tunnel By Nov. 15, the FDA is expected to release its decision on CorMedix’s New Drug Application for DefenCath, a proprietary antimicrobial formulation being proposed to cut the risk of catheter-related bloodstream infections associated with the use of central venous catheters. DefenCath leverages the strong antimicrobial properties of taurolidine, a derivative of the amino acid taurine, which has demonstrated potent activity against both gram-positive and gram-negative bacteria—including strains that have gained antibiotic resistance. Taurolidine is also effective against several clinically important fungi, including Aspergillus. DefenCath also uses the anticoagulant heparin. The FDA has already twice rejected DefenCath, both times citing manufacturing issues. The first Complete Response Letter (CRL), filed in March 2021, pointed to “concerns at the third-party manufacturing facility” detected during a review of records obtained from the third-party service provider. CorMedix received the second CRL in August 2022, which likewise flagged issues at a contract manufacturing organization (CMO) and with the supplier of heparin. In March, the company announced that both the CMO and heparin supplier had implemented corrective actions in accordance with the FDA’s inspection. However, at the time, it was unclear whether a formal resolution of the warning letter for the supplier was required for the NDA’s approval. The FDA accepted CorMedix’s resubmission for DefenCath in June and classified it as a complete Class 2 response. Two Acrotech Cancer Assets Face ODAC The FDA’s Oncologic Drugs Advisory Committee (ODAC) is scheduled to convene on Nov. 16 to discuss two cancer products from Acrotech Biopharma: Folotyn (pralatrexate) and Beleodaq (belinostat), both for the treatment of relapsed or refractory peripheral T-cell lymphoma. Both drugs are currently on the market under the FDA’s accelerated approval pathway. Folotyn won its regulatory approval in October 2009, while Beleodaq was approved in July 2014. The treatments were still owned by different companies at the time, but Acrotech bought them in 2019—along with five other drugs—for $300 million. To stay on the market and earn full regulatory approval, drugs approved under the accelerated pathway must show additional evidence of clinical efficacy in follow-up confirmatory trials. However, according to a September 2022 report from the Department of Health and Human Services’ Office of the Inspector General, both drugs have already gone past the originally planned completion dates for their confirmatory studies. At the time of the report, Beleodaq was 15 months overdue, while Folotyn was delayed by 72 months. On Thursday, the ODAC will receive updates on these two drugs and will deliberate on next steps. The panel will also have a more general discussion on delayed confirmatory trials under the accelerated approval pathway. Anticipating Rejection, Aldeyra Awaits Decision on Dry Eye Drug By Nov. 23, the FDA is set to release its decision on Aldeyra Therapeutics’ NDA for its investigational RASP inhibitor reproxalap, which the company is proposing as a treatment for dry eye disease. However, in an SEC filing posted last month, the Massachusetts-based biotech said it was anticipating a rejection from the regulator. According to Aldeyra, the FDA flagged “substantive review issues” with reproxalap’s application during a late-cycle review meeting, noting that the company does not appear to have enough “data to support the clinical relevance of the ocular signs” to support approval in this indication. Aldeyra has since responded to the FDA’s concerns, but the regulator has not yet indicated whether the additional information submitted is sufficient, and has suggested that Aldeyra might need to conduct an additional clinical trial to support its application. Reproxalap, an orally available small-molecule drug, works by covalently binding to and inhibiting reactive aldehyde species (RASP), a key driver of inflammation in the eye. In December 2021, the Phase III TRANQULITY study showed mixed results for reproxalap, which missed its primary endpoint of reduction in ocular redness but led to significant improvements in the Schirmer test, a measure of tear production. Aldeyra ran a subsequent trial called TRANQUILITY-2, which did not have ocular redness as a primary measure of efficacy and instead relied on tear production and a responder analysis. Reproxalap met both of these endpoints. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com. For more great regulatory insights from BioSpace, sign up for our weekly ClinicaSpace newsletter: