By Frank J. Sasinowski & James E. Valentine –
On August 29, 2017, FDA approved Chemo Research’s NDA for benznidazole for treatingchildren with Chagas disease and granted the sponsor a Tropical Disease Priority Review Voucher (PRV) (see FDA Press Release here). This is the first drug to treat Chagas disease, a life-threatening parasitic disease that affects an estimated 6 to 8 million people worldwide. This blog post explores key regulatory developments that may be important precedents for sponsors developing many other types of drugs.
FDA’s Accelerating Use of Accelerated Approval
Research conducted by Hyman, Phelps & McNamara, P.C. (HP&M) attorneys reported that FDA has been extraordinarily flexible in applying the quantum of evidence needed forAccelerated Approval (Subpart H, Fast Track) (see blog post & full text paper here). When published in 2016, the HP&M analysis described 19 therapies approved for other than AIDS or cancer under Subpart H. The benznidazole approval brings the current count ofsuch FDA accelerated approvals to 25 (see Approval Letter here), with the other 5more recent Subpart H approvals for Jadenu, Ferriprox, Praxbind, Ocaliva, and Exondys 51.
Jadenu (March 2015) for treatment of chronic iron overload due to blood transfusions in patients 2 years of age and older and for the treatment of chronic iron overload in certain patients 10 years of age and older with non-transfusion-dependent thalassemia syndromes
Ferriprox (Sept. 2015) for the treatment of patients with transfusional iron overload due to thalassemia syndromes when current chelation therapy is inadequate
Praxbind (Oct. 2015) indicated in patients treated with Pradaxa when reversal of the anticoagulant effects of dabigatran is needed for emergency surgery/urgent procedures and in life-threatening or uncontrollable bleeding
Ocaliva (May 2016) for the treatment of primary biliary cholangitis in combination with ursodeoxycholic acid (UDCA) in adults with inadequate response to UDCA or in adults unable to tolerate UDCA
Exondys 51 (Sept. 2016) for the treatment of amenable patients with Duchenne Muscular Dystrophy
Dr. Woodcock and others have expressed interest in expanding the use of this approval pathway and it appears to be happening. The Chagas approval is the 6th Subpart H approval in past 30 months, as contrasted with 19 approved in over 30 years before March 2015.
FDA Reaching out to and Responding to Patients in Drug Development
On April 28, 2015, FDA hosted a Patient-Focused Drug Development (PFDD) meeting on Chagas disease. Like other PFDD meetings, it gave individuals living with that disease and their loved ones an opportunity to share their experiences, including its impacts on daily life and their ability to manage the symptoms and burdens of the disease. During the meeting’s public comment period, HP&M’s Frank Sasinowski was the only speaker representing the global patient community. In his testimony on behalf of the Argentinian-based patient organization, Mundo Sano, he urged FDA, among other things, to provide incentives (i.e., Tropical Disease PRV) for Chagas disease. With FDA’s growing commitment to utilize the voice of the patient to set the context for assessing benefits and risks of new drugs (see previous coverage of the PFDD initiative here), the understanding of the disease shared by individual patients and caregivers, as well as by Mundo Sano, are likely to have been key contributors to FDA’s flexibility in assessing the data relied upon by Chemo Research in its 505(b)(2) NDA (see Labeling here).
Expanding Tropical Diseases Eligible for a PRV
At the time Chemo Research began doing the work to establish the evidence to support an NDA for benznadazole, Chagas disease was not on the list of tropical diseases eligible for a PRV. As mentioned above, FDA opened its doors to the Chagas patient community. Shortly after the PFDD meeting, we noted in a blog post (here) how Chagas disease was a good candidate for this incentive program. It is thought that one of the outcomes of Agency officials hearing from patients and Mundo Sano is that FDA decided to add Chagas to the list, which the Agency did just four months after the PFDD meeting (via a mechanism to add tropical diseases to the program under section 524(a)(3)(R) of the Federal Food, Drug, and Cosmetic Act – see previous post here).
Setting Precedent for Using PRV to Improve Patient Access
Not only was the patient community engaged with regulators (as discussed above), Mundo Sano was also a partner to Chemo Research in the development of benznidazole, along with support from the Drugs for Neglected Diseases initiative (DNDi), a non-profit drug development organization. As part of the collaboration, Chemo Research has committed that “a substantial portion of any revenue derived from the future sale of the PRV will be directed towards enhancing access to treatment of Chagas patients and improving patient health in other disease areas” (see Mundo Sano press release here). Given the scrutiny that the PRV programs have been under, redistributing funds from the sale of PRVs to patients in need, especially in tropical diseases which are endemic in lower income regions of the world (e.g., Latin American countries with Chagas disease). This type of socially responsible behavior by drug sponsors may help to maintain this incentive so that it can continue to encourage development of drugs.