Gottlieb, Fein Discuss COVID-19, Accelerated Approvals, and Drug Pricing at Asembia 2022

During a wide-ranging interview at this year's Asembia Specialty Pharmacy Summit, former FDA Commissioner Scott Gottlieb, MD, and Adam Fein, PhD, CEO of Drug Channels Institute, discussed the state of the COVID-19 pandemic, the approval of Aduhelm (aducanumab) for Alzheimer disease, and the United States’ uptake of biosimilars.

Lessons From COVID-19

According to Gottlieb, the pandemic will eventually move into an endemic phase “when we no longer have continuous waves of infection.” Currently, the nation finds itself in a transition phase and in the future, it’s likely the virus will follow the same path as the flu, in a seasonal pattern.

Because of this, yearly vaccinations will be likely. Comparing the COVID-19 vaccine to the flu immunization, Gottlieb explained that although yearly flu vaccines are recommended, this is due to the fact that “you only need 6 months of protection from the flu.” The continuous waves of COVID-19 distinguish it from the flu, but once enough immunity is seen in the population, these waves should ebb.

However, despite a cautiously optimistic outlook on the future of the pandemic, the 2 panelists took a look back at lessons learned during the public health emergency, with the CDC’s botched initial testing strategies and woefully under sourced public health infrastructure standing out as major failures.

“We didn’t have an infrastructure that was prepared for this,” Gottlieb said. “We didn’t have an agency that was charged with sort of quarterbacking a response.”

In the past, the CDC and federal agencies had expended resources preparing for a flu pandemic, he explained, but even then, during the Zika outbreak in 2015, the highly sequential process laid out for testing and tracing “barely worked.”

When the outbreak of COVID-19—a fast-moving respiratory pathogen—began in March 2020, it was clear the process in place for Zika was not going to work, he explained.

“CDC quickly tried to pivot towards mass production of testing deployed to the public health labs. Even if they had pulled that off successfully, that wouldn't have been enough. But they botched their tests,” he said.

Contamination in the CDC’s own lab drastically limited ability to scale up testing, while the only reason testing did eventually ramp up was because the agency was able to obtain kits from a company creating components of PCR tests for research use only. Working with the FDA, the kits were rapidly approved for patient use.

Overall, the lack of capacity to scale necessary tools hindered the nation’s response, leading to increased pushes for domestic manufacturing. Gottlieb anticipates congress will contract “to have a call option on a substantial amount of biologics manufacturing capacity,” in the future to better ensure supply for Americans at the outset of the next public health crisis.

Efforts to improve and prepare for the next pandemic have been slow, in part because it may be too early to move past the reaction phase.

“Part of the challenge also is that it's going to be hard to get a consensus around major reforms in the public health infrastructure,” Gottlieb said, noting this is compounded by a pervasive distrust of health officials in Washington D.C.

According to Gottlieb, the distrust transcends party lines, as Americans feel public health agencies’ response to the pandemic was incompetent and at times overbearing, lacking justification for enforcement.

Using the 6-foot rule as an example, Gottlieb explained how this recommendation remained long after it was established COVID-19 was an airborne illness. “You can be 6 feet or 16 feet [apart], if you were in the wrong place at the wrong time with poor air circulation, you were going to get infected.”

Despite this, the CDC continued with their social distancing recommendations, which in Gottlieb’s view “was the single costliest public health measure that was imposed during the pandemic,” in terms of forcing businesses and schools to shut.

Based on lessons learned, Gottlieb anticipates the CDC will pivot to become more of a national security organization and suggests shifting its work on disease prevention to other agencies to ensure its focus is more directly aimed at disease control.

Aducanumab and Accelerated Approvals

Touching on one of the more talked about actions of the FDA in recent years, Fein brought up the topic of Biogen's Alzheimer disease drug aducanumab. Following a CMS decision to only cover the drug in the context of clinical trial administration, Biogen CEO Michel Vounatsos today announced he will step down from the company.

Abstaining from commenting on whether the drug should have been approved in the first place, Gottlieb explained how the decision was consistent with previous FDA guidance, which conceded that as the biology of the brain gets understood better, there will be potential for drugs to intervene earlier in the course of these diseases, and these treatments will need to be based on biomarkers other than measures of cognitive function.

“By the time a patient is registering a discernible difference on a cognitive test, they've already accrued so much irreversible damage to their cognitive function, they’re going to be permanently impaired,” Gottlieb said.

To develop drugs that can intervene earlier to prevent patients from getting to this point, surrogate measures of disease progression are needed.

With regard to Alzheimer disease, debate still continues as the whether amyloid plaque formation is a consequence of the disease, something that drives it, or both.

Every other element of the decision to approve Aduhelm was consistent with FDA guidance, beside the fact the agency decided evidence was sufficient to consider amyloid plaque a reasonable surrogate to use as a basis of approval, Gottlieb said.

Following the saga, criticism of the accelerated approval process as a whole has increased, Fein noted, a consequence that could have substantial implications for the specialty drug pipeline and patients.

More sponsors may also refrain from going down this pathway as compared with full approval, because for larger companies, they may see full approval yield increased coverage and reimbursement in addition to placement on formularies.

When it comes to CMS’ coverage decision for Aduhelm, they agency cited the drug’s entrance through accelerated approval as a reason not to grant full coverage, a move contested by Gottlieb. Because of this, he anticipates state Medicaid and commercial plans will follow suit.

“I think what you're going to see is more companies making the decision not to pursue accelerated approval, and that's deleterious to patients,” because it’s limiting the earlier availability of drugs for unmet medical needs.

Because the biology of the efficacy of drugs for certain patient populations is so much more well understood now than in the past, FDA granting of accelerated approval and breakthrough therapy designations are more common.

“The mechanism of disease and how the drug intervenes is so well worked out in advance that in many cases, we've seen very outsized benefits in very early stage studies,” Gottlieb said.

As public antipathy toward pharmaceutical companies also revolves around drug prices, Gottlieb noted the debate of accelerated approval has evolved into a proxy debate over drug pricing in general.

High costs of drugs preclude the public to hold their efficacy to a very high standard, he explained. “And there's a perception that a drug coming though accelerated approval isn't being held to an appropriately rigorous high standard for the amount of money that the drug’s ultimately going to cost.”

An additional fallout of CMS’ decision on Aduhelm coverage may be that more individuals will move out of Part B to get out from under the coverage decision making of the agency, at least outside of the oncology setting, Gottlieb said.

Biosimilars

US adoption of biosimilars has been slower than that seen in Europe, with the lack of true interchangeability posing a major hurdle, according to Gottlieb. Formularies are not permitted to do automatic switches based on price negotiations, nor are pharmacists permitted make the decision for patients.

Interchangeability also is not the same as the AB drug rating for generic drugs, posing a hurdle for biosimilar adoption, while different states have different laws about how they treat interchangeable products.

However, recent data illustrate providers are becoming more and more comfortable with switching patients on biosimilars, and progress has been made with regard to insulin.

“As we get better and better tools for evaluating biologics, generally, you can have automatic substitution for some of the simple biologics and sort of work their way up to complexity over time,” Gottlieb said.

Looking forward, cell and gene therapy innovation, in addition to biosimilar advances, will help drive down costs and improve outcomes in a wider range of diseases, he said.