Congressional Panel Takes Deep Dive Into Future of FDA’s Accelerated Approvals

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WASHINGTON — The House Energy and Commerce Subcommittee on Health panel Thursday spent the majority of their time considering the future of the Food and Drug Administration’s so-called Accelerated Approval Program.

A number of the 20 different health care-related bills discussed by the subcommittee figure in some way in the future of the FDA’s AAP.

Rep. Brett Guthrie, R-Ky., noted during the hearing that the FDA has approved 50 new therapies since 2017, with 27 of the approvals going to first-in-class drugs and 26 having been developed to treat rare diseases.

Of the 50 new drugs, 76 were approved in the U.S. before any other country, he said.

“One of the most publicly reported approvals was for Biogen’s Aduhelm … and it has been estimated this historic approval would benefit between 1 million and 6 million Americans living with early-onset Alzheimer’s, individuals who now have some hope of treatment against this vicious disease.

“Approval of this new Alzheimer’s treatment through the accelerated approval pathway could lead to other potential benefits, including the development of more effective treatments, while encouraging investments in finding a cure for this terrible disease,” Guthrie said. “Despite its real promise, the Centers for Medicare and Medicaid Services is now attempting to only allow access to the approved drug to a very limited patient population.

“If CMS moves forward with this plan, access to Aduhelm and future FDA-approved Alzheimer’s disease treatments would be restricted for Americans with intellectual disabilities, such as Down syndrome, and patients with other neurological conditions.

“This could have a chilling effect on investment in Alzheimer’s research moving forward,” Guthrie continued. “Instead of adding more red tape, we should be focused on developing policy solutions that are intended to break down regulatory barriers and promote more collaboration between the regulatory community and the private sector.”

As it happens, Guthrie is the sponsor of another bill that was on the subcommittee’s agenda, the Pre-Approval Information Exchange Act.

“This would help address what’s known as the valley of death — the time between when a drug or device is approved by the FDA and when it is covered by the payer,” he said.

“The bill would specifically allow drug and device sponsors to share key health care economic information, including preclinical trial results and other important information, with health insurers and other payers before a drug or device is approved by the FDA,” he explained.

“This should help patients gain access to potentially lifesaving treatments such as Aduhelm more quickly, by giving the marketplace a chance to price in therapies working towards FDA approval.

“In fact, the FDA even acknowledged the potential impact these communications could have by releasing guidance in 2018, allowing these communications to occur,” Guthrie said. “Codifying this guidance would instill further confidence in the marketplace and provide needed regulatory certainty to the companies and payers already engaged in these information exchanges.

“Additionally, in the case of Aduhelm, we should also be promoting policies that will help ensure patients are receiving timely access to breakthrough therapies without significantly increasing the cost of care for our health care system,” he said.

“Reps. [Kurt] Schrader, D-Ore., [Markwayne] Mullin, R-Okla., and I have been working on a bipartisan proposal that would permit state Medicaid programs to enter into value-based purchasing agreements.

“These payment models would have dual benefits,” Guthrie said. “They could promote greater access to some of the most expensive treatments on the marketplace for lower income populations, while also helping shield state budgets against having to pay for a drug if it fails to meet its clinical endpoints. This latter point is especially important when we’re talking about accelerated approvals.”

Clinical Trials and Oversight

But House Energy and Commerce Chair Frank Pallone, D-N.J., said the bio pharmacological industry bears some of the responsibility for the flags raised in some quarters about the AAP.

One of the provisions of the program is that a drug under evaluation must be shown to have a “positive effect” on a so-called surrogate endpoint. These endpoints can include a lab measurement, an ultrasound image or even a physical sign that is reasonably likely to predict a clinical benefit.

“After being approved under the accelerated pathway, the drug’s sponsor is responsible, under FDA regulations, for conducting a well-controlled clinical trial to confirm that an actual clinical benefit exists for patients,” he said. “Unfortunately, however, under the current system, some sponsors have failed to conduct trials in a timely manner.”

Cartier Esham, Ph.D., chief scientific officer for the Biotechnology Innovation Organization, a pharmaceutical industry association of which Biogen is a member, said key legislative and regulatory reforms, like the Prescription Drug and Biosimilar User Fee Acts and the 21st Century Cures Act have collectively ensured effective and timely reviews, improved the safety monitoring of new drugs and biologics, and enabled the FDA to keep pace with medical and scientific advancements.

This legislation has also allowed for earlier and more frequent engagement between the FDA and drug sponsors to identify and resolve drug and biologic development challenges, and provide the support necessary to ensure that advanced medicines are provided to patients as quickly and safely as possible.

“The COVID-19 pandemic has shown us that decentralized clinical trials, digital health technology tools, and other innovations utilized during the pandemic have the potential to improve how we develop medicines that meet the needs of patients and greatly reduce the burden on clinical trial participants,” Esham said.

“This is especially true for those who belong to historically underserved populations and for those who suffer from rare diseases, where clinical trial populations are small and geographically dispersed,” she said, urging the panel to timely enactment of the PDUFA VII Commitment Letter to “continue to advance meaningful integration of the patient voice and experience into drug development and review processes, build upon important lessons learned from the pandemic, and pave a path forward to building a clinical development paradigm that is more effective, more informative and more inclusive.”

She also went on to say that her organization continues to strongly support the accelerated approval program for reviewing safe and effective therapies that address critical unmet patient needs.

“This pathway has proven to be very effective in addressing some of the most pressing public health needs and has been foundational to extending and saving countless lives since its enactment,” she said.

“As of June 2021, 269 new drugs or biologics to treat serious or life-threatening diseases or conditions with high unmet medical needs have been approved through this pathway, extending, and in certain cases, saving patients’ lives by providing novel therapies earlier than would have been possible using the traditional pathway,” Esham continued.

“Medicines approved under this pathway must still meet FDA’s well-established approval standard of safety and effectiveness,” she said. “The AAP is essential to providing timely access to treatments where there is an unmet need and for patients who do not have any available treatments.”

Like Pallone, Esham acknowledged the AAP requires sponsors to conduct studies to confirm a continued demonstration of benefit and evaluation of risk.

“The FDA has the authority to withdraw a treatment from the market if it determines that the benefit has not been confirmed or it is determined that the risk outweighs the benefit,” she said. “To ensure that the design and implementation of confirmatory trials are more effective, the PDUFA VII Commitment Letter provides avenues for earlier and timely discussions on the design of postmarket requirements, which are critical to confirming the clinical benefits of products receiving accelerated approval.

“Patients have consistently voiced their support of the use of AAP over the last 30 years,” Esham continued. “We have all seen how this pathway has led to more timely access to treatments that improve, extend and save lives, and has been foundational to continued advancements in the treatment of serious and life-threatening diseases.

“BIO looks forward to working with the committee to ensure that the Accelerated Approval [Program] is working efficiently, effectively and as intended,” she said.

A New Agency in the Works

Other bills discussed by the subcommittee related to the FDA’s AAP include the Cures 2.0 Act, introduced last November by Reps. Fred Upton, R-Mich., and Diana DeGette, D-Colo., aiming to ensure that federal public health agencies work seamlessly together to move new cures through the research stage all the way to FDA approval and Medicare coverage.

The 173-page bill, three years in its development, includes several provisions intended to speed the delivery of groundbreaking and potentially lifesaving treatments and cures to those who need them.

Among other things, the legislation would create an entirely new agency aimed at ending some of the world’s most difficult diseases.

The Advanced Research Projects Agency for Health would be housed within the National Institutes of Health under their proposal and tasked with finding new cures and treatments to a slate of illnesses that affect tens of millions of Americans across the country, diseases such as cancer, diabetes, ALS, multiple sclerosis and Alzheimer’s.

Subcommittee Chair Anna Eshoo, D-Calif., has introduced a stand-alone bill to authorize the creation of ARPA-H that takes a slightly different approach to setting up the new agency.

Eshoo’s bill would establish ARPA-H, modeled after the Department of Defense’s highly successful Defense Advanced Research Projects Agency, outside of the NIH, and would provide $3 billion in funding beginning in FY 2022, while allowing for advanced appropriations in future years.

In February the three lawmakers joined forces to advance their bills, hoping that taken together their various provisions will revolutionize the nation’s biomedical research capabilities and create the new advanced research agency for health.

In addition, Pallone and Ranking Member Cathy McMorris Rodgers, R-Wash., have each proposed changes to the FDA’s AAP, while several other members have proposed bills to streamline the development and approval processes for drugs, especially for rare diseases and pediatric cancers.

This article was produced in partnership with and paid for by BIO, the Biotechnology Innovation Organization.