Theory can outrun reality on drug approval fast track
Generally, when a pharmaceutical company announces that one of its drugs has been granted fast-track designation by FDA, it’s considered good news. If the company is publicly traded, the stock may rise. But Brian Orelli, a biotech analyst who provides commentary for investment website The Motley Fool, thinks people shouldn’t get too excited about fast-tracking — but they almost always do.
For example, last week FDA granted GW Pharmaceuticals fast-track designation for its treatment for Dravet syndrome, a severe form of childhood epilepsy. Shares of GW jumped considerably. However, according to Orelli, most of the fast-tracked drugs come out around their PDFUA date anyway. Rolling submissions — in which companies are able to submit completed sections of their applications instead of waiting until the entire NDA or BLA is completed — can be helpful, but whether fast-tracking provides a significant benefit is not entirely clear.
"While the designation sounds good — who doesn't want faster drug approvals? — fast-track designation is relatively easy to get and says more about the unmet need of the disease the drug treats than it does about the drug itself," Orelli wrote.
Pathways to faster approval
Getting fast-track designation is one of four distinct ways to expedite the drug review and approval process. From a humanitarian perspective, expediting approval means that patients with serious medical conditions can get access to the therapies sooner than they would otherwise. Each of the four pathways differs, but all are designed to expedite the approval and availability of drugs for the treatment of serious diseases. In many cases, a company may have more than one designation for a specific drug aimed at a specific indication.
Fast-track designation is granted to drugs that, if approved, will have an impact on patients’ survival or daily functioning. In addition, there must be an unmet medical need where there is either no therapy available or there are patients who cannot tolerate existing therapies and would benefit from the new drug. Also if a drug can be used as part of a combination regimen that improves the standard of care than it qualifies for fast-tracking. The designation is also granted to drugs that can increase compliance or that address an existing or imminent public health need.
A recent example of fast-tracking is Lymphoseek, a diagnostic device that is used to help physicians visualize sentinel lymph nodes in patients with cancer. FDA granted fast-track status to Lymphoseek earlier this month for use in detecting squamous cell carcinoma in the head and neck. Lymphoseek was first approved by FDA nine months ago — for the detection of cancerous breast and melanoma cells. Because of the broad need for diagnostic accuracy in oncology, Lymphoseek qualified for fast-track designation in both cases.
Breakthrough therapy and accelerated approval
Breakthrough therapy is more specific than fast-track designation. Though it is also designed to expedite review and approval, getting this designation requires preliminary evidence based on a specific clinical endpoint that suggests substantial improvement over existing therapies.
Novartis’s meningitis B vaccine, Bexsero, received breakthrough designation from FDA based on the strength of evidence provided by the Centers for Disease Control and Prevention (CDC) on 8,000 vaccinated individuals, as well as the fact that there is currently no approved vaccine against the strain B virus.
During the last four months, Novartis has provided 30,000 doses of Bexsero to students at Princeton and UCSB. In this case, having a preventive vaccine represents an improvement over not having any treatment options, especially considering the recent public health threat. Drugs that are granted breakthrough therapy status automatically have all the benefits associated with fast-track designation.
Accelerated approval allows drugs that have been developed for the treatment of a serious unmet medical need to be approved based on surrogate endpoints. Because it takes a fairly long time to establish clinical benefit, accelerated approval can speed things along. Sometimes, however, it’s difficult to determine whether a particular surrogate is appropriate.
In May 2013, Sarepta Therapeutics announced that it would pursue accelerated approval for eteplirsen, for the treatment of Duchenne muscular dystrophy. The company chose to use dystrophin protein as a surrogate marker for Duchenne muscular dystrophy; however, FDA questioned that decision. Sarepta countered that eleptirsen has shown evidence of both efficacy and safety---and that those results track with changes in dystrophin protein.
Priority review designation
Finally, priority review designation is granted under PDUFA V regulations. A drug qualifies if its approval would significantly improve the safety or efficacy of a treatment, diagnosis or prevention compared with existing options. Gilead applied for priority review when it submitted the NDA for the fixed-dose ledipasvir/sofosbuvir (LDV/SOF) combination tablet on Feb. 10 for the treatment of chronic hepatitis C genotype 1 infection. LDV/SOF qualifies because of its intended use in a special subpopulation with a serious medical condition. FDA has set the target action date as Oct 10.
In the final analysis, many industry executives bemoan the long approval process that seems to drag on despite PDUFA fees and other strategies. If expending the process using one these four methods helps a company achieve a decision by the PDUFA date that in and of itself is a good thing -- though there certainly is room for improvement.