This past summer, Congress passed and President Obama signed the Food and Drug Administration Safety and Innovation Act (FDASIA) and Section 902, which created a “breakthrough therapy” designation designed to expedite the development and review of a drug when it is intended “to treat a serious or life‐threatening disease or condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on 1 or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.”
This new “breakthrough pathway” is offering a select number of companies a chance at a shortcut to the market based on early-stage data for transformational new therapies. “So when Janet Woodcock, the influential director of the FDA’s Center for Drug Evaluation and Research (CDER), started outlining how the program will work–indicating that a company can move from an expanded Phase I directly to commercialization, Bloomberg reporters were paying close attention. “Improved understanding of diseases is leading to more candidates for this status.”
In December 2012, Woodcock lauded the submission of the first breakthrough product requests. “We’re delighted now to have another tool to help expedite the development and approval of products with the ‘breakthrough’ designation,” Woodcock wrote. “We’ll continue to use our existing tools and the new ‘breakthrough’ authority to make our expedited drug development process even more effective, with the ultimate goal of benefiting patients with unmet medical needs.”
Despite the new pathway and designation, FDA did not “receive authorization to hire more full-time employees for the enhanced communication and is attempting to balance its priorities.” “We don’t want to disadvantage ordinary drugs,” Woodcock said.
According to the business news wire, Woodcock says that companies which earn breakthrough status will have the ear of the agency. “We expect many of these would come available very quickly with Phase I data,” she said. This would likely need to be a “robust Phase I clinical trial.” FDA has already assigned three experimental medicines the new status to try to reduce the time needed to get them to market against deadly diseases.
Vertex has won breakthrough status for two drugs for cystic fibrosis, the approved drug Kalydeco and the experimental VX-809, now being studied as a combination therapy. According to Woodcock, a third drug has been anointed with the special status. “And developers have submitted 18 for review, most of which are for cancer.”
The third drug is an experimental therapy for blood cancers being manufactured by Pharmacyclics Inc. and its partner, New Brunswick, New Jersey- based Johnson & Johnson. They will submit the therapy, ibrutinib, to FDA for approval before the end of the year, the companies said today in separate statements, reported Bloomberg.
“This is a historic moment in oncology,” Bob Duggan, chief executive officer of Sunnyvale, California-based Pharmacyclics said in the statement. “We are truly honored to have received this breakthrough designation and are pleased for patients and clinicians with the FDA’s decision to expedite the development of ibrutinib.”
Ibrutinib blocks an enzyme called Bruton’s tyrosine kinase that aids certain cancers in spreading. The drug has breakthrough status for patients with Waldenstrom’s macroglobulinemia, and mantle cell lymphoma patients that have failed other therapies. Pharmacyclics said it’s currently testing the drug in five late-stage trials.
Mantle cell lymphoma is a type of B-cell non-Hodgkin lymphoma that typically strikes older adults, with about 5,000 new cases each year, Pharmacyclics said. Waldenstrom’s macroglobulinemia is a rarer type of lymphoma that affects 1,500 people a year and there are no approved treatments.
In a related post on FDA’s Voice blog, the agency discussed its various attempts at reducing drug development time and bringing safe and effective new therapies to Americans as efficiently as possible.
The pointed to FDA’s “expedited development” tools, which help foster new drug innovation during the investigational phases of drug research and development, well before a marketing application for a new drug is even submitted to FDA. Among these tools are more frequent and earlier opportunities for communication between FDA and drug developers. FDA’s Fast Track designation for drugs with the potential to address unmet medical needs is an example. For many years, Fast Track has helped speed new drug development by encouraging more communication early in the development process. In 2012, about 40% of CDER’s novel new drug approvals were drugs that were given this Fast Track designation.
The post also explained that the concept behind the “Breakthrough” designation is “increased communication”; “FDA will work with new drug developers to help design efficient ways to study the safety and effectiveness of their drug. This early assistance can help ensure that the results of clinical trials provide the evidence that FDA must have to determine whether or not a drug is safe and effective for approval. A growing number of drug developers are already taking advantage of Breakthrough.”
But even before Breakthrough had been authorized by FDASIA, “FDA was working to encourage communication opportunities for drug developers to meet with FDA to help make sure their clinical trial designs and development plans offered the best chances of efficient, safe, and timely development and approval. These opportunities are available at the start of a drug’s clinical development cycle: right before the earliest phases of human testing known as the “pre-investigational new drug (IND) phase” (fittingly called pre-IND meetings) and continue throughout drug development.”
Recently, FDA has taken a look at the development times of new drugs that were approved with the benefit of pre-IND meetings and compared them to the development times for drugs that were approved without such meetings. The findings underscore the value of early communication. For those new drugs for which a pre-IND meeting between the drug developer and FDA was held, average clinical development times were substantially shorter than when a meeting was not held. For instance, for all new drugs approved between 2010 and 2012, the average clinical development time was more than 3 years faster when a pre-IND meeting was held than it was for drugs approved without a pre-IND meeting.
For orphan drugs used to treat rare diseases, the development time for products with a pre-IND meeting was 6 years shorter on average or about half of what it was for those orphan drugs that did not have such a meeting. Early communication is especially important for orphan drugs because these products require special attention and thus early talks can be especially beneficial.
“Many factors can influence the speed and efficiency of a drug development program. Nevertheless, FDA strongly believes in the value of effective communication during the drug development and approval process, especially for novel development programs when established regulatory pathways do not exist. FDA is committed to working with drug developers to ensure efficient and effective drug development programs whenever possible.”