The former FDA commissioner and Asembia keynote speaker was sanguine about the future course of the COVID-19 pandemic and biosimilars. He is concerned, though, that the CMS Aduhelm coverage decision set a bad precedent.
Scott Gottlieb, M.D., said the COVID-19 virus might be running out of its bag of tricks, but the voluble former FDA commissioner didn’t run short of topics to discuss today as the keynote speaker at the 2022 Asembia Specialty Pharmacy Summit in Las Vegas
In a fireside chat format with Adam Fein, a well-known drug industry and pricing expert, Gottlieb’s comments ranged predictions from about the course of pandemic to the CDC’s shortcoming to biosimilars to drug rebates. Some of his sharpest words were directed at CMS’ decision to limit coverage of Aduhelm (aducanumab), which Gottlieb said may set a precedent for limited coverage for other drugs given accelerated approval by the FDA.
Fein introduced Gottlieb as a “voice of reason” and one of three people he follows on Twitter. The large ballroom at Wynn Convention Center was full.
Gottlieb sketched a picture of COVID-19 pandemic settling into a seasonal pattern resembling flu. He said, though, that one of the big questions is whether dominant form of the coronavirus that causes COVID-19 will remain one in the omicron lineage or emerge from a divergent evolutionary path. Gottlieb, who is frequent comments on COVID-19 for CNBC and other news channels, said that “we are starting to see the virus mutate in the way that is has mutated before.”
“It is running out of its bag of tricks, or so it seems,” he added.
Gottlieb’s 2021 book, Uncontrolled Spread: Why Covid-19 Crushed Us and How We Can Defeat the Next Pandemic, was critical of the CDC’s response to the pandemic, and Gottlieb repeated some of that criticism today. He said the agency was organized to develop tests for new diseases in a “highly sequential process” that was overwhelmed by the COVID-19 pandemic. Gottlieb said the agency was inept in following its own, flawed process: “They literally contaminated their own lab.”
Gottlieb noted the lack of any report, commission or investigation of the public health response to the pandemic. He said he favors orienting the agency toward becoming a national security organization and perhaps delegating some of its prevention efforts to other agencies. He also spoke about a“hot base of preparedness” for the next pandemic that, in his view, would entail the government contracting with private manufacturers to maintain extra capacity in their systems that could be turned over to the government when there is a public health crisis. Gottlieb said manufacturers could overbuild or perhaps, as Regeneron did, freeze a large amount of bulk products so the manufacturing facility could be devoted to the government’s needs in an emergency, He also said it was important to maintain domestic manufacturing. He recounted how during the H1N1 flu pandemic, manufacturers in Canada and Australia were making vaccine for the U.S., but the governments there wouldn’t release the vaccine to the U.S. until their local needs were met. “ Similarly, shipment of vaccine being manufactured in North Carolina for the U.K. was delayed until the British prime minister got involved.
“The lesson is that if you want to have a supply for your country at the outset of a public health crisis you are going to need to manufacture it in your own country,” Gottlieb said,
Gottlieb, who is on Pfizer’s board of directors, didn’t get into a detailed discussion of the merits of the FDA’s decision to approve Aduhelm (aducanumab) in July 2021. But he said the agency’s OK was very consistent with a 2018 guidance by the part of the agency that oversees drugs for neurodegenerative diseases such as Alzheimer’s. The guidance recognized the need for drugs that would address the pathology of Alzheimer’s disease before it manifested itself in declines in cognitive function that can be measured by tests such as the Min-Mental State Examination. The effectiveness of such drugs needs to be measured with surrogate markers that are correlated with the decline, and Gottlieb noted the lack of those for Alzheimer’s. Beta-amyloid plaque formation has been candidate, but FDA and others have questioned whether the evidence for it was strong enough.
“The FDA changed its view on the science and in the context of the Aduhelm decision they said, ‘We how have sufficient evidence, based in part on the data generated in the context of this review that we know believe plaque formation is a reasonable surrogate.’ That is what changed,” Gottlieb told the Asembia audience. Every other element of the Aduhelm was very consistent with that 2018 guidance.”
The agency’s approval of Aduhelm has led to criticism of accelerated approval. Gottlieb said legislation to tighten up the requirements for confirmatory studies may result. He also said that while small companies with investors that want a return will continue to pursue accelerated approval, larger, well-capitalized companies may hold back and pursue full approval because it is a safer from commercial cost-benefit point of view.
But Gottlieb defended accelerated approval based on smaller, early-stage trials as a reflection of better understanding of the biology of many illnesses and the stronger scientific understanding of medications can target an underlying disease process. “The mechanism of the disease and how the drug intervenes is so well worked out in advance that in many cases you have seen outsize benefits in early-stage studies,” Gottlieb said. Much of criticism of accelerated approval is a “proxy discussion” about high drug prices, he said.
Gottlieb was critical of CMS decision to limit coverage of Aduhelm to patients who are enrolled in clinical trials, although CMS did broaden requirements for acceptable trials in its final decision in April to include any trial approved by the FDA or the National Institutes of Health. Gottlieb said the CMS decision was predicated, at least in part, on Aduhelm getting accelerated approval. As FDA commissioner, Gottlieb said he worked with the then-CMS Administrator Seema Verma to successfully push back on plan by the state of Massachusetts’ Medicaid program to limit coverage of drugs that had received accelerated approval. “Now CMS has opened the barn door to this kind of policy making,” said Gottlieb. “You are going to see state Medicaid plans follow suit and you are going to eventually see commercial plans and they are going to use accelerated as the sole basis for not putting a drug on formulary.”
Gottlieb said another long-term effect of the CMS Aduhelm decision may Medicare Part B as a market for new drugs. Historically, he said. Part B was seen as an avenue to automatic coverage and CMS, a price taker.
“I think more and more companies are going to realize that maybe Part B is not such a good deal anymore.”
But shifting to biosimilars, Gottlieb sounded an optimistic note. He called the less expensive versions of expensive biologics as being “largely a success story” even if the “on ramp” has been longer in the U.S. than in Europe. He said some characterizations of the limited effect of biosimilars on prices have misleading because they didn’t take into account the lowering of the prices of the brand-name, “originator” drugs in response to biosimilar competition.
Gottlieb also said the technology has advanced so that for simple biologics, such as insulin, the physical structures can be compared. He said that technology could be used to establish therapeutic equivalence and true interchangeability, so a less expensive drug could be substituted for a more expensive one at the pharmacy level.
Gottlieb also fielded Fein questions on drug prices and rebates. Rebates have been justified as lowering premiums, but Gottlieb said he wasn’t sure that was as true as it used to be and that rebates are now increasing seen by PBMs and others as a separate revenue stream that doesn’t necessarily translate into lower premiums. He said the gap between gross and net drug prices created by rebates is narrowing. “The pharmaceutical companies realize that has become a major political vulnerability.”
Gottlieb also gross-net difference is “moving in better direction” and with that, for the PBMs to start focusing on providing services and medical management.