Medicare's National Coverage Determination Could Boost Chances of Limited Aduhelm Coverage

Biopharmaceutical Report II



Issue24_September 2021


By opening a National Coverage Determination (NCD) on Biogen’s (NASDAQ:BIIB)

Aduhelm (aducanumab) for Alzheimer’s disease, Medicare has signaled a willingness to

provide some level of coverage in the US without outright denying its use.


Typically, the Center for Medicare & Medicaid Services (CMS) makes coverage decisions through Local Coverage Determinations (LCDs), which largely remain unnoticed. NCDs are normally employed for controversial medical technologies.


However, in the case of Aduhelm, a former CMS official said an NCD is a promising

sign for Biogen. Since the drug has faced uniquely intense public scrutiny, most LCDs

would have denied coverage to avoid controversy. However, an NCD signals the CMS’

openness to significantly restricting the drug without completely denying coverage.


Given the thorough, transparent process of an NCD, the CMS could confidently stand

behind a decision to provide limited coverage in the face of political pressures, a

healthcare regulatory consultant explained. The CMS’ best tool for narrowing

coverage—the rarely used Coverage with Evidence Determination (CED) process—is

only available via an NCD, a bioethicist added. A CED would only provide Aduhelm

coverage to patients in open-label studies or enrolled in future studies and planned

clinical trials, subject to the population coverage restrictions applied by the CMS.


Nevertheless, there has been a trend toward more stringent NCDs and increased pressure

to avoid the same kind of controversy as the FDA faced following its Aduhelm approval,

adding uncertainty to the process.


On 29 July, the expected nine-month NCD process began with an open public comment

period. Biogen did not respond to a request for comment.


National determination could be a positive sign


Under an NCD, all Medicare Administrator Contractors (MACs)—which normally make

Medicare coverage decisions on the regional level—are bound to follow the NCD

outcome. Historically, NCDs are extremely rare for drugs, with almost all NCDs taking

place for medical devices, said James Chambers, PhD, researcher, Center for the Evaluation of Value and Risk in Health, Tufts Medical Center, Medford, Massachusetts.

Chambers, who has researched trends in NCDs, noted NCDs, have almost always

provided coverage for FDA-approved therapies but occasionally deny coverage for

devices.


Given the unprecedented backlash against Aduhelm, the safest and most likely decision

from MACs would be to deny Aduhelm coverage because its evidence does not meet

Medicare coverage requirements, the former CMS official, now a regulatory consultant,

said. As a result, the decision to pursue an NCD is likely a positive sign for Biogen, he

explained. By pursuing this route, the CMS has signaled the tools available in an NCD

are more useful for granting some Aduhelm coverage than if the issue were left to

regional MACs, he said.


Nevertheless, LCDs give the manufacturer multiple opportunities to gain regional

coverage without the risk of national noncoverage as a result of one NCD, Chambers

noted. However, the CMS normally strongly considers the impact of any debilitating

condition on patients and their families in its coverage decisions, the former official

noted. And as a result, an NCD is very unlikely to deny Aduhelm coverage without first

pursuing every possible route to providing some form of limited coverage, he said.

Additionally, although Biogen has requested for MACs to make coverage decisions while

awaiting the NCD, it is unlikely any MAC would make a coverage decision given all the

attention Aduhelm garners, the former CMS official said.


CED route last resort over denial


If the evidence gathered in the NCD process opposes Aduhelm, the CMS would likely

cover the drug under CED over an outright coverage denial, the former CMS official

said.


Although the CED process is exceedingly rare and normally unexpected for an FDA-

approved drug, the unprecedented scrutiny of the Aduhelm decision and competing

political pressures make it a much more likely outcome, said a Medicare healthcare

consultant. Still, this decision would be largely unprecedented, as a CED designation is

typically reserved for “close call situations” when the CMS decides more evidence is

needed for a Medicare-specific population, the former CMS official explained.


Even with a CED, it is debatable whether additional data collected outside of a

randomized control trial would be valuable, Chambers noted. Because Aduhelm is

intended to slow disease progression rather than stop or reverse progression, it is unclear

if patients who experience cognitive decline on Aduhelm are gaining no benefit, or if

they would have been worse without it, said bioethicist Leonard Fleck, PhD, professor,

Center for Bioethics and Social Justice, Michigan State University, East Lansing.


In a November 2020 FDA Advisory Committee meeting, Aduhelm’s efficacy was

overwhelmingly rebuked by a panel of experts and biostatisticians. However, in June, the FDA granted Aduhelm accelerated approval after determining the demonstrated

reduction in amyloid plaque is “reasonably likely” to translate to clinically meaningful

improvement on cognitive decline.

As part of the accelerated approval process, Biogen has nine years to complete a confirmatory trial establishing whether a reduction in amyloid plaque does in fact translate to clinically meaningful disease outcomes. If the trial fails to do so, the FDA could remove marketing authorization for Aduhelm.



"If the evidence gathered in the NCD process opposes Aduhelm, the CMS would likely cover the drug under CED over an outright coverage denial"

Precedent for narrower label


On 7 June, the FDA granted Aduhelm accelerated approval for all Alzheimer’s disease

patients, despite clinical testing only covering mild patients. Still, in an 8 July press

release, Biogen said Aduhelm should be used in patients with “mild cognitive impairment

or mild dementia stage of disease.”


Beyond this initial narrowing, if the CMS does not pursue the CED route in favor of

greater coverage, the coverage would likely come with even further restrictions, the

former CMS official said. The CMS has several options available for limiting

aducanumab’s use, including restrictions on age groups, disease severity, disease

biomarkers, and who can prescribe the treatment, the health care consultant explained.


Beyond the NCD label decision, the growing scrutiny of Aduhelm will likely further limit

the label, said George Perry, PhD, Semmes Foundation Distinguished University chair in

Neurobiology, University of Texas, San Antonio. Clinicians will be reluctant to prescribe

the drug given its safety and efficacy concerns, and it is likely many would try and sway

patients against its use, Perry explained.


Medicare hampered by bargaining, cost analysis restrictions


In an ideal scenario, Medicare would cover Aduhelm at the price of manufacturing, at

approximately USD 2,500–5,000, plus a modest profit for Biogen, Fleck said. However,

given the enormous restrictions on Medicare, this outcome is far from likely, he noted.

Medicare cannot negotiate prescription drug prices, nor does it explicitly consider cost in

its coverage decisions, Chambers explained. The FDA is tasked with determining if a

drug is “safe and effective,” while the CMS determines if a drug is “reasonable and

necessary,” with no specific mandate related to cost-effectiveness. Biogen announced Aduhelm will have a list price of USD 56,000 per patient per year. However, to be cost-

effective, the Institute for Clinical and Economic Review (ICER) independently

determined Aduhelm should be priced at USD 2,950–8,360 per person per year.


Overall, the NCD process can only determine if and to what extent a drug should be

covered, and it does not deal with the amount Medicare will reimburse for a specific drug

or device, the former CMS official explained. As a result, considering Medicare’s many

restrictions and the unprecedented scrutiny surrounding Aduhelm, the NCD process’ flexibility to provide some level of coverage in the face of mounting criticism could be

the best sign for Biogen, he said.




Prophylactic antibiotics may be a valuable tool to extend survival


Another possible way to help increase Pepaxto’s OS data is to use prophylactic

antibiotics, Martin said. Triple-class refractory multiple myeloma patients are already

fragile, having gone through many prior lines of therapy on top of having low bone

marrow reserves, he explained. And Pepaxto can further negatively impact these reserves,

increasing risk of infection, he added. And so, preventive antibiotics might be able to

help.


Apart from prophylactic antibiotics, another way is to increase these patients’ leukocyte

count, especially neutrophils, to be able to combat infections, Mellqvist added. Pepaxto’s

FDA label warns of thrombocytopenia, neutropenia, anemia and infections, among

others. Patients who end up with neutropenia become highly sensitive to infections, and

severe cases can be fatal, Martin explained.


But the spokesperson noted OCEAN did allow for antibiotics as prophylaxis and was

recommended in both arms. While prophylactic antibiotics might be helpful, Schjesvold

said that the number of infections in OCEAN between arms is not dramatically different.

Pomalyst had slightly more infection events than Pepaxto in OCEAN, according to a 26

May company presentation.


OCEAN efficacy data still worth digging into


While it was judicious for the FDA to pause ongoing Pepaxto trials on the back of new

OS data, there is still potential for the treatment to be used in its present setting where

there are currently limited options, experts said. In OCEAN’s primary endpoint,

progression-free survival (PFS), final analysis shows Pepaxto was superior to Pomalyst

(p=0.0311).


In OCEAN, while the OS data might favor Pomalyst, the confidence interval of the

hazard ratio shows it may not be a definitive finding, Schjesvold added. The hazard ratio

for OS of Pepaxto versus Pomalyst was 1.104, with a 95% confidence interval range of

0.846 and 1.441.


"While it was judicious for the FDA to pause ongoing Pepaxto trials on the back of newm OS data, there is still potential for the treatment to be used in its present setting where there are currently limited options"

However, based on available data so far, it might be challenging for Pepaxto to

demonstrate dramatic superiority over Pomalyst in the OS endpoint, Schjesvold said.

Pomalyst is a high bar, in contrast to Pomalyst’s registrational trial which only compared

it to steroids, Mellqvist noted. Pomalyst was FDA approved in multiple myeloma in

2013.


Oncopeptides has a SEK 3.08bn (USD 358.1m) market cap.





William Newton

Reporter, New York


William Newton is a healthcare reporter for GlobalData focusing on central nervous system diseases and ophthalmology. Previously, he worked at the healthcare information firm Close Concerns, where he covered breaking news in diabetes therapeutics and technology for the company’s industry-facing publication, and at the digital health startup Fitscript, where he assisted in researching digital health and lifestyle intervention approaches to treating diabetes. He graduated Williams College with a BA in Economics and Spanish and worked as a News Editor, Executive Editor, and Managing Editor of the Williams Record.