The FDA Priority Review Designation: A Primer

Picture1By Peter Martin, M.D.

Under the Prescription Drug User Act the FDA created a two-tiered system for review of new drug applications (NDA). The first tier of this system, known as Standard Review, is for treatments that offer a minor improvement over existing therapies, and sets the timeline to review at 10 months from receiving the NDA. The second tier, the Priority Review, is for drugs that offer major advances over existing therapies, or provide a treatment where none had previously existed, and reduces the approval timeframe of review to 6 months.

Significant improvements over pre-existing treatments include evidence of increased effectiveness in treatment, prevention, or diagnosis, reduction in treatment-limiting reactions, evidence of safety and effectiveness in a new patient population, and documented enhancement of patient compliance that is thought to lead to an improvement in serious outcomes.

Unlike other expedited approval programs with different levels of standards the Priority Review designation does not change the scientific or medical standards used for approval by the FDA. Instead more resources are devoted to expediting approval for the treatments that receive this designation because the FDA has decided chosen treatments serve a much greater need. To receive the Priority Review designation the FDA requires evidence of increased effectiveness in treatment prevention, or diagnosis of a condition.

Previous Entries in the Primer Series

The FDA Approval Process
The FDA Breakthrough Therapy Designation
THE FDA Accelerated Approval Designation

Treating Mantle Cell Lymphoma: Why Are Patients Benefitting From New Therapies?

Picture1By Peter Martin, MD

Most clinicians and researcher agree since mantle cell lymphoma (MCL) was first described 25 years ago patient outcomes have improved considerably. What remains unknown, however, is why outcomes are improving.

In an international, phase III clinical trial from the European MCL Network that was recently published in The Lancet, investigators demonstrated that progression-free survival could be doubled by the addition of rituximab, dexamethasone, cytarabine, cisplatin (R-DHAP) to standard chemotherapy and autologous stem cell transplantation. Whereas in the early 1990s, data suggested that patients might expect to live for 2-4 years, new findings demonstrated that patients can achieve decade long remissions. The strange thing about this remarkably positive study is that the overall survival was similar in both arms despite significant differences in virtually all other outcome measures. In fact, in the vast majority of MCL related phase III trials, despite great improvements in depth and duration of response, the overall survival of the experimental and control arms is the same.

While we celebrate the successes that each of these studies represents, important questions remain. Why are the patients in the control arms doing so well? Why are patients treated with the older, less effective therapies living as long as patients randomized to receive new therapies, and why are they living longer than patients receiving those therapies a couple decades ago?

Some of these questions can be answered by perception biases and advances in supportive care. For example, if patients in 2016 are being diagnosed with MCL earlier than they might have been diagnosed in the 1990s, they would appear to live longer, a phenomenon known as lead-time bias. Improvements in pathology may also lead to what is known as selection bias. Previously, patients with less aggressive variants of MCL were misdiagnosed as having other kinds of lymphoma, while a more representative sample is included in today’s studies. Similarly, perhaps people enrolled in recent clinical trials are healthier than they were in the past, another form of selection bias. Perhaps supportive care has improved, allowing people to live longer with lymphoma, or tolerate therapies that might have been considered overly aggressive in the past. If any or all of these hypotheses are true, hematologists around the world cannot claim credit for the perceived improvements.

It is clear that people with MCL are living longer with a higher quality of life. They have more options for treatment and these gains are due to clinical trials. In the past decade, the use of rituximab has expanded while bortezomib, temsirolimus, ibrutinib, and lenalidomide, all better tolerated than many historical options, have been approved. If this is true, it suggests that the path to continued improvements relies on the development of new, well-tolerated approaches, and it suggest that front-line therapies without curative potential must evolve to become less toxic so that subsequent lines of therapy remain feasible.

New Clinical Trial: Phase 2 Study Evaluating the Efficacy/Safety of PQR309 in Patients with Relapsed/Refractory Lymphoma

The Weill Cornell Medicine Lymphoma Program has recently opened a new clinical trial for men and women with relapsed/refractory lymphoma. The study sponsor is PIQUR Therapeutics AG, and the principal investigator at Weill Cornell is Lisa Roth M.D. For more information about the study, please call Catherine Babaran, RN at 212-746-2651 or e-mail Catherine at cmb9017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older with histologically confirmed diagnosis of relapsed or refractory lymphoma who have received at least two prior lines of therapy including immuno-chemotherapy. Patients with relapsed chronic lymphoid leukemia (CLL) are eligible if they have received one or more prior lines of any approved standard therapy.
  • Detailed eligibility reviewed when you contact the study team.

Study Summary

This clinical trial is for men and women with relapsed or refractory lymphoma. Despite conventional therapies, such as chemotherapy and radiation therapy, the treatment of lymphomas remains challenging, with the disease relapsing in many patients, which is subsequently more difficult to treat. The main goal of this study is to investigate the efficacy of PQR309 in patients with relapsed or refractory lymphomas. This is an open-label, non-randomized, multicenter phase 2 study with a safety run-in evaluating efficacy and safety of PQR309 in patients with relapsed or refractory lymphoma. There will be a safety run-in phase with up to 12 patients treated with 60 or 80 milligrams every day and then a Phase 2 expansion phase conducted with the highest dose level considered to be safe.  Patients will take 60 mg or 80 mg PQR309 orally once daily and will continue treatment as long as they are responding to therapy and not experiencing unacceptable side effects.