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Leveraging Fda's Accelerated Pathways for Market

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Leveraging Fda's Accelerated Pathways for Market WHITE PAPER LEVERAGING FDA’S ACCELERATED PATHWAYS FOR MARKET ADVANTAGE Over the past 15 years, the FDA and Congress developed several accelerated pathways to provide incentives for manufacturers to develop innovative new drugs to treat conditions with substantial unmet need. The objective of this white paper is to describe recent trends in the use of the FDA’s accelerated pathways and to examine the market advantage associated with these pathways, particularly in oncology. OVERVIEW OF ACCELERATED PATHWAYS TAGRISSO® was granted four accelerated pathways (Figure 1). The IND for TAGRISSO® was filed in June 2013, Several acts of legislation overhauled the regulatory and TAGRISSO® was awarded fast track designation process for drug approvals in the US and enabled in November 2013. Based on its Phase 1 data showing the FDA to create expedited programs and special disease control in 94% of patients, TAGRISSO® was designations to stimulate and accelerate novel drug granted breakthrough designation in April 2014.1 In development (Table 1). Collectively, these programs September 2014, the FDA granted TAGRISSO® orphan and designations have become known in the industry as drug designation. The NDA for TAGRISSO® was filed on “accelerated pathways.” a rolling basis, with the first portion submitted January Different accelerated pathways focus on different 2015 and the third and final portion submitted in June ® characteristics of drugs and target indications, and 2015, and TAGRISSO was awarded priority review. ® drugs may qualify for more than one pathway. The focus Finally, in November 2015, TAGRISSO was granted and benefits of the different pathways are summarized accelerated approval for the treatment of EGFR T790M in Table 2. mutation-positive metastatic non-small cell lung cancer (NSCLC) who have progressed on or after EGFR tyrosine AstraZeneca’s TAGRISSO® (osimertinib) is an example kinase inhibitor (TKI) therapy.2 Approval was granted of how a manufacturer can use multiple pathways based on two Phase II studies showing a complete or to significantly accelerate development timelines. partial reduction in tumor size (i.e., objective response Table 1. Legislation Establishing FDA Accelerated Pathways FDAMA FDASIA Orphan Drug Act PDUFA I (under PDUFA II) (under PDUFA V) 1983 1992 1997 2012 Purpose • To simulate interest • To address "drug • To recognize the • To expand FDA's in drug development lag" in the US changes in which authorities, promote for orphan diseases FDA will operate in innovation, and that affect <200,000 the 21st century increase stakeholder people involvement Key Elements • Provided incentives • Authorized collection • Established: • New user fees to manufacturers: of user fees to – Clinicaltrials.gov for generic and – Development increase scientific biosimilar drugs staffing and – Biologic License grants Application (BLA) • Incentives for upgrade information antibiotics (GAIN Act) – 50% tax credits technology systems for clinical trial expenses • Reauthorized every 5 years – 7 year market exclusivity Accelerated • Orphan drug • Priority review • Fast track • Breakthrough Pathways designation designation designation Introduced • QIDP designation • Accelerated approval • Rare pediatric disease priority review voucher Source: FDA Guidance on Expedited Programs for Serious Conditions, May 2014. YOUR JOURNEY. OUR MISSION.® | 2 Table 2. Summary of FDA Accelerated Pathways Pathway Focus Benefits Impact Orphan • Drugs that target rare diseases • FDA guidance on protocol • As of 2015, Designation or conditions affecting <200,000 development for clinical trials 437 drugs were people in the US • Development grants approved with orphan designation • Small trial sizes (compared to 10 in • Eligibility for accelerated approval 1982) or priority review • PDUFA fees waiver • 7 years of market exclusivity • Tax credits • Priority review vouchers for rare pediatric disease approvals Priority • Drugs that provide a significant • Shortened review of marketing • Median time to Review1 improvement in safety or application (6 months vs. 10-month approval was effectiveness for a serious standard review) reduced from 19 condition (1993) to 10 months (2012) Fast Track • Drugs that demonstrate the • Frequent interactions with the FDA • As of 2015, Designation potential to address unmet and the possibility for rolling review 114 drugs were medical needs for a serious and/or priority review approved with or life-threatening disease or fast track condition Breakthrough • Drugs that target a serious • Intensive guidance on efficient • As of 2015, Designation or life-threatening disease or clinical trial design, frequent 22 drugs were condition, where preliminary interaction with the FDA, and the approved with clinical evidence indicates possibility for rolling review and/or BTD substantial improvement over priority review existing therapies Qualified • Antibacterial and antifungal • Potential eligibility for fast track • As of 2015, Infectious drugs intended to treat serious designation and, priority review 6 drugs were Disease and life-threatening infections upon submission of an NDA or approved with Product (QIDP)2 supplement for that use QIDP Accelerated • Drugs that target a serious • Early approval based on an effect • As of 2015, Approval or life-threatening disease or of the treatment on a surrogate 74 drugs were condition, where a surrogate endpoint or an intermediate clinical approved with AA endpoint is reasonably likely to endpoint that is reasonably likely to predict clinical benefit predict a drug's clinical benefit 1. Not explicitly an accelerated pathway, but strongly associated with use of accelerated pathways 2. Not analyzed in this paper since priority review is usually applied for at the time of NDA filing rather than during development Source: FDA Guidance on Expedited Programs for Serious Conditions May 2014, PAREXEL Biopharmaceutical R&D Statistical Sourcebook 2015/2016. YOUR JOURNEY. OUR MISSION.® | 3 Figure 1. Regulatory Timeline for TAGRISSO® Figure 2. Stacking of Accelerated Pathways among New Drug Approvals in FDA* Breakthrough Designation 50 PhI data shows Accelerated Approval 45 Number of FDA disease control in Treatment of EGFR-T790M Accelerated positive patients who have 41 Pathways 94% of patients 39 progressed on or after TKI 40 therapy (2L) 4 pathways Fast Track Orphan Designation Designation 30 30 27 3 pathways Approved 2 pathways 2013 2014 2015 2016 2017 2018 20 1 pathway Roche Cobas V2 test was IND Filed / Phase II NDA approved as a companion No pathway Phase I initiated Filed New Drugs diagnostic to enable monitoring 10 initiated the status of EGFR T790M Time to Market (~2.5 yrs) 0 Source: Health Advances analysis, FDA, company press releases. 2011 2012 2013 2014 2015 *Pathways tracked include orphan, fast track, breakthrough, qualified rate), a surrogate endpoint. By leveraging all possible infectious disease product, and accelerated approval. accelerated pathways and executing a highly efficient Source: Health Advances analysis, FDA New Drug Summary (2011-2015). development plan, TAGRISSO® was able to compress its clinical development and regulatory approval timelines, MARKET ADVANTAGES OF ACCELERATED reaching the market only 2.5 years after IND filing, a PATHWAYS remarkable achievement compared to the industry average of approximatley 8 years. Regression analysis of all oncology drugs approved between 2011 and 2015 shows that breakthrough RECENT TRENDS IN THE USE OF designation is associated with commercial benefits in ACCELERATED PATHWAYS terms of shorter time to market, defined as time from IND filing to FDA approval, and higher projected peak Of the 182 new drugs approved by the FDA between 2011 sales, based on EvaluatePharma® projections (Figure 4). and 2015, 103 (57%) drugs participated in at least one Specifically, breakthrough designation is associated of the FDA’s accelerated pathways. 71 drugs received with higher projected peak sales of over $1.0B (p<0.01) orphan drug status, 69 drugs received fast track and reduced time to market by ~2.8 years (p=0.04). Fast designation, 23 drugs received accelerated approval, track designations also have positive effects, but these 22 drugs received breakthrough designation, and are not statistically significant. Accelerated approval 6 drugs received QIDP designation.3 The stacking does not show statistically measurable effects, but this of designations has increased over time, especially is likely due to designation stacking: at least 86% of following the introduction of breakthrough designation breakthrough designation oncology drugs also received in 2013 (Figure 2). fast track designation, accelerated approval, or both, so the benefits of accelerated approval are captured in the Oncology drugs, which account for a substantial share benefits ascribed to the other pathways.4 of new drug approvals in recent years, received the majority of accelerated pathway designations (Figure 3). When the stacking of accelerated pathways was Stacking multiple accelerated pathways was a common considered, oncology drugs that received fast track trend among oncology drugs. Among oncology drugs designation, breakthrough designation, and accelerated receiving accelerated approval, all but one (IBRANCE® approval were associated with higher projected (palbociclib) for ER+ breast cancer) were orphan peak sales of nearly $1.4B (p = 0.01) relative to drugs drugs, and most also received fast track designation, without these stacked designations. The stacking of breakthrough designation,
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