The testing and approval process requires
substantial time, effort and financial resources, and the receipt and timing of any approval is uncertain. Given this paradigm,
AD has been given a Life Threatening Disease status by the FDA and therefore AD therapies are eligible for the expanded access
program for investigational drugs and other pathways like Breakthrough Therapy, Accelerated Approval and Priority Review. Also,
a single well-designed, well-conducted pivotal clinical study could be sufficient to trigger market approval pending a successful
Pre-clinical studies include laboratory
evaluations of the product candidate, as well as animal studies to assess the potential safety and efficacy of the product candidate.
The results of the pre-clinical studies, together with manufacturing information and analytical data, are submitted to the FDA
as part of the IND, which must become effective before clinical studies may be commenced. The IND will become effective automatically
30 days after receipt by the FDA, unless the FDA raises concerns or questions about the conduct of the studies as outlined in the
IND prior to that time. In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical studies
Clinical studies involve the administration
of the product candidates to healthy volunteers or patients with the disease to be treated under the supervision of a qualified
principal investigator. Clinical studies are conducted under protocols detailing, among other things, the objectives of the study,
the parameters to be used in monitoring safety, and the efficacy criteria to be evaluated. A protocol for each clinical study and
any subsequent protocol amendments must be submitted to the FDA as part of the IND. Further, each clinical study must be reviewed
and approved by an independent institutional review board, or IRB, either centrally or individually at each institution at which
the clinical study will be conducted. The IRB will consider, among other things, ethical factors, the safety of human subjects
and the possible liability of the institution. There are also requirements governing the reporting of ongoing clinical studies
and clinical study results to public registries. The FDA, the IRB or the clinical study sponsor may suspend or terminate clinical
studies at any time on various grounds, including a finding that the subjects or patients are being exposed to an unacceptable
health risk. Additionally, some clinical studies are overseen by an independent group of qualified experts organized by the clinical
study sponsor, known as a data safety monitoring board or committee. This group provides authorization for whether or not a study
may move forward at designated check points based on access to certain data from the study. We may also suspend or terminate a
clinical study based on evolving business objectives and/or competitive climate.
Clinical studies are typically conducted
in three sequential phases prior to approval, but the phases may overlap. These phases generally include the following:
Phase 1. Phase 1 clinical studies represent
the initial introduction of a product candidate into human subjects, frequently healthy volunteers. In Phase 1, the product candidate
is usually tested for safety, including adverse effects, dosage tolerance, absorption, distribution, metabolism, excretion and
Phase 2. Phase 2 clinical studies
usually involve studies in a limited patient population to (1) evaluate the efficacy of the product candidate for specific indications,
(2) determine dosage tolerance and optimal dosage and (3) identify possible adverse effects and safety risks.
Phase 3. If a product candidate is
found to be potentially effective and to have an acceptable safety profile in Phase 2 studies, the clinical study program will
be expanded to Phase 3 clinical studies to further demonstrate clinical efficacy, optimal dosage and safety within an expanded
patient population at geographically dispersed clinical study sites.
Phase 4 clinical studies are conducted
after approval to gain additional experience from the treatment of patients in the intended therapeutic indication and to document
a clinical benefit in the case of drugs approved under accelerated approval regulations, or when otherwise requested by the FDA
in the form of post-market requirements or commitments. Failure to promptly conduct any required Phase 4 clinical studies could
result in withdrawal of approval.
The results of pre-clinical studies and
clinical studies, including negative or ambiguous results as well as positive findings, together with detailed information on the
manufacture, composition and quality of the product, are submitted to the FDA in the form of an NDA requesting approval to market
the product. The NDA must be accompanied by a significant user fee payment. The FDA has substantial discretion in the approval
process and may refuse to accept any application or decide that the data is insufficient for approval and require additional pre-clinical,
clinical or other studies.