Special Protocol Assessment
The FDA and an IND sponsor may agree in
writing on the design and size of clinical studies intended to form the primary basis of a claim of effectiveness in an NDA. This
process is known as a special protocol assessment, or SPA. Upon a specific request for a SPA by an IND sponsor, the FDA will evaluate
the protocol. If a SPA agreement is reached, however, it is not a guarantee of product approval by the FDA or approval of any permissible
claims about the product. The FDA retains significant latitude and discretion in interpreting the terms of the SPA agreement and
the data and results from any study that is the subject of the SPA agreement. In particular, the SPA agreement is not binding on
the FDA if previously unrecognized public health concerns later come to light, other new scientific concerns regarding product
safety or efficacy arise, the IND sponsor fails to comply with the protocol agreed upon, or the relevant data, assumptions, or
information provided by the IND sponsor when requesting a SPA agreement change, are found to be false statements or misstatements,
or are found to omit relevant facts. A SPA agreement may not be changed by the sponsor or the FDA after the study begins except
with the written agreement of the sponsor and the FDA, or if the FDA determines that a substantial scientific issue essential to
determining the safety or effectiveness of the drug was identified after the testing began.
Orphan Drug Designation
Under the Orphan Drug Act, the FDA may
grant orphan designation to a drug or biological product intended to treat a rare disease or condition, which is a disease or condition
that affects fewer than 200,000 individuals in the US, or if it affects more than 200,000 individuals in the US there is no reasonable
expectation that the cost of developing and making a drug product available in the US for this type of disease or condition will
be recovered from sales of the product. Orphan product designation must be requested before submitting an NDA. After the FDA grants
orphan product designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA.
Orphan product designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.
If a product that has orphan designation
subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled
to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug or biological
product for the same indication for seven years, except in limited circumstances, such as a showing of clinical superiority to
the product with orphan exclusivity. The designation of such drug also entitles a party to financial incentives such as opportunities
for grant funding towards clinical study costs, tax advantages and user-fee waivers. Competitors, however, may receive approval
of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but
for a different indication for which the orphan product has exclusivity. Orphan product exclusivity also could block the approval
of one of our products for seven years if a competitor obtains approval of the same drug or biological product as defined by the
FDA or if our drug candidate is determined to be contained within the competitor’s product for the same indication or disease.
If a drug product designated as an orphan product receives marketing approval for an indication broader than what is designated,
it may not be entitled to orphan product exclusivity. Orphan drug status in the European Union has similar but not identical benefits
in that jurisdiction.
Disclosure of Clinical Trial Information
Sponsors of clinical trials (other than
Phase 1 trials) of FDA-regulated products, including drugs, are required to register and disclose certain clinical trial information.
Information related to the product, comparator, patient population, phase of investigation, trial sites and investigators and other
aspects of the clinical trial is made public as part of the registration. Sponsors are also obligated to disclose the results of
their clinical trials after completion. Disclosure of the results of certain trials may be delayed until the new product or new
indication being studied has been approved. However, there are evolving rules and increasing requirements for publication of trial-related
information, and it is possible that data and other information from trials involving drugs that never garner approval could in
the future be required to be disclosed. In addition, publication policies of major medical journals mandate certain registration
and disclosures as a pre-condition for potential publication, even when this is not presently mandated as a matter of law. Competitors
may use this publicly available information to gain knowledge regarding the progress of development programs.