In response to the global threat of increasingly difficult-to-treat infections, many government incentive programs have emerged to encourage the development of new anti-infectives, making infectious disease both an increasingly appealing social and business value-driver that benefits patients and the health system alike.
Increased global awareness of the increasing incidence of multi-drug resistance has driven major improvements in the regulatory environment for new infectious disease medicines, which are driving new interest and investment in this therapeutic area. In addition, there are significant grants and other non-dilutive funding opportunities, allowing many infectious disease programs to be advanced in a capital-efficient manner. Because Appili is not bound to a specific indication or platform technology, we are free to pursue a broad range of opportunities targeting unmet needs in the infectious disease space.
Major improvements have emerged in the regulatory environment, including transferable priority review vouchers and additional years of market exclusivity to protect development investment. Additionally, anti-infectives are often eligible for ‘priority review’ and ‘fast track’ designation to expedite the regulatory process, accelerating the time-to-market for novel agents.
Significant private/public sources of funding have emerged for both broad (multidrug resistant antibiotics and anti-fungals) and specific (bioterrorism or globally endemic threats) programs.
There is an increased global awareness of the problems related to antibiotic resistance. The U.S. Centers for Disease Control and Prevention (CDC) and World Health Organization (WHO) have issued reports analyzing the significant ‘security threat’ of antimicrobial resistance, and designating the development of better anti-infectives as a top priority for global public health.
Priority Review Vouchers (PRV)
The PRV program is an incentive for companies to invest in new drugs for underserved patient populations through the granting of transferable vouchers. Once issued, a PRV can be applied to any subsequent drug development program and reduce NDA review time to as little as six months. Voucher eligible programs include:
Novel agents for the treatment of neglected tropical diseases, including viral hemorrhagic fevers, cryptococcal meningitis, and leishmaniasis
New vaccines and therapies targeting major biodefense threats such as anthrax, tularemia, and smallpox
The PRV program has had a significant impact on the pharmaceutical industry and has accelerated innovation in government priority areas. Vouchers provide a major competitive advantage to the holder, as transferable assets have significant monetary value. At least 16 PRVs have been sold since the program was initiated in 2007, with an average selling price in excess of $130M. Voucher sale prices have ranged from $67.5M to $350M. The most recent PRV transaction was reported in Q4 2019, with Bavarian Nordic selling its PRV for $95M.
The National Institutes of Health's (NIH) National Institute of Allergy and Infectious Diseases (NIAID) provides additional dedicated funding for costs related to early development activities, including preclinical development, manufacturing, and Phase 1 clinical, safety and pharmacokinetic evaluation
The CARB-X program provides $350M U.S. in funds for early development costs for new antibiotics to address today’s largest bacterial threats.
The 21st Century Cures Act
The U.S. Congress passed the 21st Century Cures Act to:
Provide additional regulatory incentives to promote the development of infectious disease therapies and vaccines
Expand the Priority Review Voucher program to include medical countermeasures for biodefense pathogens
Introduce the Limited Population Antibacterial (LPAD) regulatory pathway, which:
Allows smaller clinical trials and increased reliance on preclinical data during regulatory review
Provides an additional pathway for streamlined antibiotic development distinct from the pathogen-focused development process outlined in the GAIN Act.
GAIN Act/QIDP Designation
The Generating Antibiotics Incentives Now (GAIN) Act defines a Qualified Infectious Disease Product (QIDP) as a new “antibacterial or antifungal drug for human use intended to treat serious or life-threatening infections, including those caused by an antibacterial or antifungal resistant pathogen, including novel or emerging infectious pathogens.”
QIDP sponsors may benefit from:
Five years of market exclusivity in addition to the periods of exclusivity for which they would otherwise qualify
Priority review that would shorten the review period to six months
Fast track designation that enable early and frequent communications with the FDA, in addition to the typical review opportunities
A specific timetable for the FDA to develop and issue final updated guidance on antibiotics clinical trials
A regulatory path for pathogen-focused antibacterial drug development rather than the disease-focused development
New Technology Add-On Payment (NTAP)
The New Technology Add-On Payment (NTAP) is a Centers for Medicare & Medicaid Services (CMS)-led system that partially reimburses hospitals for the costs of new technologies, like novel therapeutics, when these costs exceed the diagnostic related group (DRG) reimbursement rates. NTAP fills the time-gap between the implementation of the innovative technologies, and the adjustment of the DRG rates to reflect the costs of these new technologies.
For a drug to be given an NTAP designation it must both be new and be an improvement over other treatment options. The program was first launched in 2001, and until recently has covered up to 50% of the costs associated with treating a patient in-excess of the DRG rate. In April 2019, CMS proposed increasing the reimbursement amount to cover 65% of the costs of new technologies. NTAP speeds up adoption of novel therapies and other technologies, greatly benefiting both patients and innovative drug development companies.