||refusal to permit the import or export of our products;|
||imposition of civil or criminal penalties.|
Accordingly, assuming we receive marketing approval
for vonapanitase or any additional product candidates, we and our contract manufacturers will continue to expend time, money and
effort in all areas of regulatory compliance, including manufacturing, distribution, product surveillance, post-marketing studies
and quality control.
Vonapanitase may cause undesirable side effects or have other
properties that could delay or prevent their regulatory approval, limit the commercial profile of approved labeling, or result
in significant negative consequences following any potential marketing approval.
As with many pharmaceutical and biological products,
treatment with vonapanitase or any additional product candidates may produce undesirable side effects or adverse reactions or events.
These adverse events may occur despite our belief, based on our preclinical and clinical trials to date, that vonapanitase has
a favorable safety profile. For instance, vonapanitase shows a high degree of structural similarity with other human serine proteases,
which are proteins that cut other proteins to activate, inactivate or degrade these other proteins, and it is theoretically possible
that if anti-vonapanitase antibodies are developed that they could cross-react with one or more of those other proteases because
of the structural similarity, and prompt an adverse reaction. However, we have not seen any evidence of such cross-reactivity in
our preclinical or clinical trials to date.
Based on our Phase 2 and Phase 3 trials, adverse
side effects that could occur with treatment with vonapanitase include fistula surgical incision pain, venous stenosis, procedural
pain, fistula thrombosis, steal syndrome and hypoesthesia. If any of these adverse events occur in rates or severity exceeding
placebo and unacceptable to regulatory authorities or IRBs, if anti-vonapanitase antibodies develop and are associated with cross-reactivity
to other proteases, or unknown serious events emerge, our clinical trials could be suspended or terminated by us, IRBs, or the
applicable regulatory authorities, and the FDA, the EMA or other foreign regulatory authorities could order us to cease further
development of, or deny approval of, vonapanitase or any additional product candidates for any or all targeted indications. The
product-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial. If we
elect or are required to delay, suspend or terminate any clinical trial of vonapanitase or any additional product candidates, the
commercial prospects of these product candidates will be harmed and our ability to generate product revenues from any of these
product candidates will be delayed or eliminated.
In addition, even if we were to obtain approval,
regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, including
more limited patient populations, may require that contraindications, warnings or precautions be included in the product labeling,
including a boxed warning, may grant approval contingent on the performance of costly post-marketing clinical trials or other post-market
requirements, or may approve a product candidate with labeling that does not include the labeling claims necessary or desirable
for the successful commercialization of that product candidate. Any of these occurrences may harm our business, financial condition
and prospects significantly.
We may not be able to maintain orphan drug designation or
obtain or maintain orphan drug exclusivity for vonapanitase.
We have obtained orphan drug designation from
the FDA for vonapanitase. In the United States, under the Orphan Drug Act, the FDA may designate a product as an orphan drug if
it is intended to treat a rare disease or condition, which is generally defined as a patient population of fewer than 200,000 individuals
annually in the United States for a preventive drug. The first NDA or BLA applicant to receive FDA approval for a particular drug
or biologic to treat a particular disease with FDA orphan drug designation is entitled to a seven-year exclusive marketing period
in the United States for that product, for that indication. During the seven-year exclusivity period, the FDA may not approve any
other applications to market the same drug or biologic for the same disease, except in limited circumstances. Orphan drug exclusivity
may be lost if the FDA determines, among other reasons, that the request for designation was materially defective or if the manufacturer
is unable to assure sufficient quantity of the product to meet the needs of patients with the rare disease or condition.