On July 11th the Oncologic Drugs Advisory Committee (ODAC) held a half-day meeting to discuss the biologics license application (BLA) 761060.
On July 11th the Oncologic Drugs Advisory Committee (ODAC) held a half-day meeting to discuss the biologics license application (BLA) 761060 for MYLOTARG (gemtuzumab ozogamicin). Gemtuzumab is a monoclonal antibody (MAB), which is indicated for use in combination therapy with daunorubicin (DNR) and cytarabine (AraC), for the treatment of adults with previously untreated de novo acute myeloid leukemia (AML). The BLA was submitted by Wyeth Pharmaceuticals, a subsidiary of Pfizer.
MYLOTARG is a MAB-drug conjugate which binds to the transmembrane receptor CD33 on AML cells. After MYLOTARG binds to CD33, the complex is then internalized into the AML cell where calicheamicin is released from the complex. The calicheamicins are a class of anti-tumor antibiotics, which results in double-stranded DNA breaks within the AML cell, subsequently resulting in complete cell death.
MYLOTARG was originally approved in the US in 2000, under accelerated conditions. The confirmatory trial for, SWOG S0106, failed to confirm the clinical benefit of MYLOTARG. Additionally, increased risk of veno-occlusive disease (VOD) identified in post-marketing surveillance, contributed to Pfizer’s decision to voluntarily withdraw MYLOTARG from the US market in 2010.
However, positive data from randomized, cooperative/group-run trials designed by investigators for use of MYLOTARG in first-line AML treatment began to emerge. This data suggested that a significant benefit was seen with MYLOTARG when administered in lower doses and/or a fractionate schedule in conjunction with chemotherapy regimens. Additionally, Wyeth identified an increasing number of AML community requests for MYLOTARG, in both the US and non-US settings, since 2010. Therefore, Wyeth assembled a comprehensive clinical data package, including their pivotal ALFA-0701 trial, as well as a meta-analysis from 5 co-op group trials and Pfizer-sponsored studies, which demonstrated a favorable benefit-risk profile for the de novo AML indication.
Wyeth concluded that administration of MYLOTARG at the lower-dose fractionated regimen improves tolerability of the drug, reduces the risk of myelosuppression/VOD risk, and demonstrates a stable safety profile in the AML patient population. Additionally, Wyeth concluded that based on the data presented, the benefit/risk of MYLOTARG is favorable in newly diagnosed AML patients.
The FDA presented the panel with one question, which was a voting question. “Do the results of ALFA-0701 demonstrate a favorable benefit-risk for gemtuzumab ozogamicin 3 mg/m2 days 1, 4 and 7 added to DA for patients with newly-diagnosed CD33-positive AML?” The vote resulted in a (6 to 1 positive result. Panel members stated that event free survival (EFS) is an acceptable clinical endpoint to utilize in de novo AML studies, which the FDA expressed some concern with in their presentation, and that the benefit of MYLOTARG, in terms of EFS has been proven. Additionally, panel members noted that the new dosing regimen has improved the safety profile for MYLOTARG, when compared to the original, and that the drug may improve the quality of life in the newly diagnosed AML patient population. The “no” vote was the result of a panel member not seeing any benefit of the new MYLOTARG regimen, as well as risk of toxicities, such as VOD.
ISS has almost two decades of experience in developing regulatory strategies including support for FDA Advisory Committee meetings. We are involved in more FDA AdComms per year than even the largest pharmaceutical companies. For more information on how ISS can help you prepare for your next meeting, contact firstname.lastname@example.org.
Over the past few years, the number of ex-US manufacturers submitting a Class II exempt 510k device registration has increased substantially. For companies with medical devices that are approved and successful in a foreign market, the logical next step is to introduce their product into the US, which has one of the most lucrative healthcare markets in the world. Read more
FDA advisory committee meetings are important regulatory events for many manufacturers on the path to marketing approval. These meetings can quite literally result in the approval or rejection of a product based on the panel’s vote. Read more
One of the main challenges our clients face is determining which regulatory pathway is best for their products. For example, what if an OTC product has a Monograph active ingredient but that ingredient is present at a different amount than the permitted amount? Or what if the label claims a novel indication not specified in a Monograph? If you are debating pursuit of either regulatory pathway for your OTC drug, it is critical to consider cost, timeline, and label claims to ensure your products has a unique stance in today’s market. Read more
US distributors and agents trying to import rapid antibody tests for coronavirus face a number of obstacles. The good news is that FDA has opened up the Emergency Use Authorization (EUA) program to include SARS-CoV-2 (the virus) and COVID-19 (the disease), expediting time to market. Read more
The journey to scientific and commercial success is often complex and always critical, if you are looking for an expert partner to help steer you to confident solutions, contact us todayContact us