[Congressional Record Volume 168, Number 106 (Wednesday, June 22, 2022)]
[Senate]
[Pages S3077-S3078]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]

      By Ms. COLLINS (for herself and Mr. Kaine):
  S. 4446. A bill to modernize the process of accelerated approval of a 
drug for a serious or life-threatening disease or condition; to the 
Committee on Health, Education, Labor, and Pensions.
  Ms. COLLINS, Mr. President, I rise to introduce the Modernizing the 
Accelerated Approval Pathway Act with my colleague from Virginia, 
Senator Tim Kaine. The Food and Drug Administration's accelerated 
approval pathway has long had broad bipartisan support and is an 
important tool that provides early access to treatments for patients 
with serious and life-threatening conditions for which there is an 
unmet need, like Alzheimer's disease, Duchenne muscular dystrophy, and 
many cancers.
  FDA grants accelerated approval based on substantial evidence that a 
surrogate end point is reasonably likely to predict a clinical benefit. 
In other words, therapies have to meet the same ``substantial 
evidence'' standard as traditional approval, but they can rely on a 
surrogate end point that predicts a clinical benefit rather than 
measuring that clinical benefit directly. For example, a study might 
measure viral load as a surrogate end point for survival in HIV or 
tumor size in oncology.
  This can considerably shorten the time required before a product 
receives FDA approval. Clinical outcomes can take significantly more 
time to manifest than a surrogate end point, and in the meantime, 
patients go without treatments while studies are being conducted. 
Sponsors are still required to complete postmarket studies for their 
accelerated approval products, which are designed to confirm the 
clinical benefit with goals of converting an accelerated approval into 
a traditional approval. A review of accelerated approval drugs approved 
between 1992 and 2016 concluded that 76.5 percent were converted to 
traditional approval.
  The accelerated approval pathway has served us well over the decades 
since it was created in response to outcry over unmet patient need 
during the HIV/AIDS crisis. More than 250 new therapies have received 
accelerated approval, with 65 percent of those therapies treating 
cancer indications and just over 40 percent treating rare diseases or 
conditions. We need, however, to make sure that we update this pathway 
so that it remains flexible in our current scientific environment and 
can continue to enable access to treatments for patients with serious 
and life-threatening conditions who are desperate for a treatment or 
cure.
  It is well known that use of the accelerated approval pathway is 
inconsistent across FDA. Some therapeutic areas, like oncology, have 
vast experience and success using the pathway. In fact, about 85 
percent of accelerated approvals between 2010 and 2020 were for 
oncology indications. In other areas, like neurological diseases, it is 
infrequently used. Patient communities are deeply frustrated by what 
they view as underutilization of the tool and feel it has created 
disparities given that the urgency of finding a

[[Page S3078]]

cure is one shared by all patients with diseases for which there is no 
treatment or cure, regardless of which bureaucratic office leads drug 
review for their particular disease. The Government Accountability 
Office has found that these inconsistencies are due in part to a lack 
of familiarity with the tools of accelerated approval in certain FDA 
centers and divisions. Our bill would correct this by establishing a 
council of senior FDA leadership to ensure consistent and appropriate 
use of the accelerated approval pathway across and within FDA centers 
and divisions.
  Although a number of rare disease therapies have been good candidates 
for accelerated approval, there can also be challenges to using the 
pathway. Sometimes a disease is so rare or heterogeneous that 
developers need to study a small subset of the population in order to 
demonstrate a treatment effect. Our bill would clarify that real-world 
evidence--data from patient registries, electronic health records, 
medical claims, and observational studies--can be used to augment or 
support appropriate post approval studies. This approach may yield 
meaningful and timely evidence that adds context to other data and 
helps us understand how a product works in the real world and across 
the entire population for a disease.
  Some have criticized the timeliness of confirmatory trials, which are 
sometimes delayed by operational or ethical challenges. FDA and drug 
developers are often rushing to agree on a confirmatory trial structure 
late in the review structure, and in those cases they may not be able 
to benefit from expert input or feasibility analyses. This can create 
untenable expectations regarding timelines or, in a worst case 
scenario, result in drug developers pursuing a flawed study that is not 
appropriately designed to confirm clinical benefit. Our bill would 
clarify that FDA may require confirmatory trials to be underway prior 
to approval and that FDA can specify the conditions for those studies, 
which may include enrollment targets, study protocol, milestones, and a 
target date for study completion. Our bill also outlines expedited 
procedures for withdrawing an accelerated approval if a confirmatory 
trial fails to confirm the clinical benefit.
  Finally, we need to make it clearer how much progress an accelerated 
approval product has made toward confirming its clinical benefit. Our 
bill would require that developers of drugs approved under accelerated 
approval submit to FDA a report of the progress they have made on 
required confirmatory trials every 180 days. It would also require that 
if FDA does not require postapproval studies for an accelerated 
approval product, the Agency must publish an explanation on its website 
as to why such a study is not appropriate or necessary.
  Our bill has support from the Juvenile Diabetes Research Foundation, 
American Cancer Society Cancer Action Network, Parent Project for 
Muscular Dystrophy, EveryLife Foundation for Rare Diseases, Alzheimer's 
Association, National MS Society, American Academy of Neurology, 
National Organization of Rare Diseases, and the Haystack Project. I 
thank Health, Education, Labor, and Pensions Committee Chairman Murray 
and Ranking Member Burr for including it in their FDA Safety and 
Landmark Advancements Act, which was favorably reported out of the HELP 
Committee this week. I encourage my colleagues to support that bill 
when it is considered on the Senate floor.
                                 ______