"One of the most tantalizing new programs now being rolled out at the FDA is its brand new category for "breakthrough" drugs, 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, 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.
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."
The FDA still has not issued guidance on its breakthrough status initiative. So far, here is what they have published.
Fact Sheet: Breakthrough Therapies
The Food and Drug Administration Safety and Innovation Act (FDASIA) includes a provision that allows sponsors to request that their drug be designated as a Breakthrough Therapy. FDA is in the process of developing guidance related to this designation. Until guidance is developed, requests for Breakthrough Therapy designation should follow the criteria outlined below. A request for Breakthrough Therapy designation should be submitted concurrently with, or as an amendment to an Investigational New Drug Application (IND) with a cover letter, a completed form 1571, and the following information:
Identification in the cover letter of the submission as a REQUEST FOR BREAKTHROUGH THERAPY DESIGNATION in bold, uppercase letters.
The IND application number, if applicable.
The proprietary and/or generic name and established name for drug products; proper name and trade name for biological products.
The division or office where the IND is being submitted to or is active.
The proposed indication(s) for your product.
A brief, but comprehensive, summary of information that justifies why your product qualifies for a Breakthrough Therapy designation for the indication being studied, including:
Evidence that the drug is intended, alone or in combination with 1 or more other drugs, to treat a serious or life-threatening disease or condition,
Preliminary clinical evidence indicating that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.
If applicable, a list of documents previously submitted to the IND that are deemed relevant to the designation request, with reference to submission dates so the documents can be readily located. Copies of such documents can be resubmitted to the FDA as appendices to the designation request (if not too voluminous).
In most cases, this information could be captured in an approximately 10-20 page document.
No later than 60 days after receipt of the submission, a determination will be made to either grant or deny the request for Breakthrough Therapy designation in the form of a designation letter (for requests granted) and a non-designation letter (for requests denied).
First, don't expect breakthrough status for CRPC. It wouldn't make sense. The two pivotal trials are underway and when results are available, the existing structure would allow a priority review to ensure a quick approval process if the data warrant expedited handling. The other problem with CRPC is that the primary evidence of efficacy is BSR and we keep running into the issue that BSR is not a validated surrogate.
But taking a look at breakthrough for other indications might lead to some interesting situations. For instance, Cabo has shown very high RECIST criteria objective response rates in DTC, and Ovarian cancer. There is also the RET mutation trial in NSCLC. If for instance the RET driven NSCLC trial showed an exceptionally high ORR ( 40%) it appears to me this would be a great candidate for breakthrough. The phase 1 IND could be expanded with extra cohorts enrolled with a SPA like understanding that a quick approval would follow with confirmed efficacy showing a high durable response rate.
Pharmacyclics announced earlier this week that the Food and Drug Administration has deemed ibrutinib a breakthrough therapy as a treatment for mantle cell lymphoma. The FDA created the breakthrough therapy program in 2012 as a way to speed up the approval process for drugs that could be significant improvements in the treatment of serious or life-threatening diseases from what's currently on the market. In 3 days after it announced, PCYC jumps 25%.