Biogen's 'shockingly broad' Aduhelm label—and $56K price—set up a $10B launch

 Biogen didn't just win the most closely watched FDA green light of the year. Its newly minted Alzheimer's drug, Aduhelm, snared an approval that covers all Alzheimer's patients, not just a select group of them, meaning millions could be eligible.

And it set an aggressive price tag, in the words of one analyst, that's several times higher than market watchers had predicted—roughly $56,000 for the average patient.

The upshot? Some $10 billion in peak sales, analysts say. And "one of the biggest launches in biopharma history."

Aduhelm, also known as aducanumab, will face its challenges. With the much-publicized controversy over its approval—including a scathing thumbs-down from an FDA advisory panel—some doctors will need convincing to prescribe it, and some patients might be skeptical as well.

Before the approval, analysts were torn on whether Biogen would score the Alzheimer’s nod at all. Some placed the drugmaker’s chances of clean approval at less than a coin flip.

But it not only scored its approval. It won a "shockingly broad" label, Bernstein analysts wrote to clients.

The FDA approved the drug for all Alzheimer's patients—totaling more than 6 million people in the U.S.—even though the drug was only studied in patients with early disease.

The agency also didn’t place a limit on treatment duration, suggesting patients could stay on Aduhelm “until either all plaque is removed or the patient progresses,” the Bernstein analysts noted. The treatment is a monthly IV infusion.

Aduhelm, under that label, has millions of patients to target, and they could all take the drug indefinitely. But there's another key variable in the launch equation—price—and Biogen came out aggressive.

Biogen set Aduhelm’s list price at $4,312 per infusion for a patient of average weight, or $56,000 per year—several times higher than experts had previously estimated. It’s well above the recommendation from the drug-cost watchdogs at the Institute for Clinical and Economic Review, which previously said Aduhelm should cost $8,300 per year—at most—given the “insufficient” evidence supporting its benefits. Several analysts had estimated the drug would cost around $10,000 per year.

Analysts have already started laying out lofty sales estimates. Aduhelm could reach $10 billion in peak sales, Bernstein analysts said in their note. Meanwhile, Cantor Fitzgerald analysts wrote that Biogen "is now set up for one of the biggest drug launches in biopharma history." The investment bank predicted peak sales of roughly $8.2 billion in 2028. 

Biogen "has the potential to generate (at least) $10 billion in peak sales" and a successful launch "has the potential to completely change the profile of the company," Guggenheim analyst Yatin Suneja said, Reuters reports. 

If one thing’s for certain, Biogen needed an FDA win for Aduhelm. The Massachusetts-based company has gone all-in on the drug amid serious troubles elsewhere in its business. Multiple sclerosis drug Tecfidera and spinal muscular atrophy med Spinraza have been facing increasing competitive pressures, dragging Biogen to a sales decline in 2020.

The FDA handed aducanumab an accelerated approval based on a surrogate endpoint—the destruction of amyloid plaques—rather than the drug's ability to slow cognitive decline. A reduction in those plaques is “reasonably likely to predict important benefits to patients,” the agency argued.

The endorsement is contingent on results from a confirmatory trial. But analysts weren't worried.

"We're confident the Street will not be overly concerned on this, and it would be done in a way that would not have significant jeopardy to stakeholders, in our view," Jefferies analysts said in a note Monday. 

Shares of Biogen, which were halted Monday morning pending the FDA's decision, jumped roughly 52% to about $434 per share once trading resumed.

Even with an agency go-ahead in hand, analysts have said that aducanumab could face a number of hurdles before it reaches patients. Physicians may be unsure who should get it and for how long, while payers may balk at its lofty price tag and erect barriers that could limit reimbursement, analysts warn.

After the approval, Mizuho analyst Salim Syed wrote to clients that there's "a lot of pressure" on payers, and that insurers could point to the drug's data to "make this difficult for doctors and patients alike." The launch "may be not be as smooth at the market is currently implying," Syed wrote.

https://www.fiercepharma.com/pharma/alzheimer-s-fda-nod-bag-biogen-faces-historic-drug-launch-and-10b-potential-sales-analysts

AstraZeneca Redefining Cancer Care in Breast Cancer, Leukemia at ASCO

 Throughout the past few days, AstraZeneca has been presenting data at the American Society of Clinical Oncology (ASCO) Annual meeting that reaffirms the company’s commitment to redefine cancer care.

In a pre-ASCO panel co-led by The Cancer Support Community, AstraZeneca asked the million-dollar question: Are we ready to talk cure in cancer? While the panelists, which included oncologists, researchers and AstraZeneca executives, didn’t come to a clear conclusion, the company is making headway in at least two indications: post-surgery, high-risk HER2-negative early breast cancer and chronic lymphocytic leukemia (CLL).

During ASCO’s plenary session on Sunday, data was presented from the OlympiA Phase III trial showing that LYNPARZA® (olaparib), the first poly ADP ribose polymerase (PARP) inhibitor to show clinical benefit in the adjuvant setting for early breast cancer, reduced the risk of invasive breast cancer recurrences, second cancers, or death by 42%.

After three years, 85.9% of patients treated post-surgically with Lynparza were free of invasive breast cancer and second cancers compared to 77.1% of the placebo group. 

“Patients with early-stage breast cancer who have inherited BRCA mutations are typically diagnosed at a younger age compared to those without such a mutation. Olaparib has the potential to be used as a follow-on to all the standard initial breast cancer treatments to reduce the rate of life-threatening recurrence and cancer spread for many patients identified through genetic testing to have mutations in these genes,” said Andrew Tutt, OlympiA trial steering committee chair and professor of Oncology at The Institute of Cancer Research, London and Kings College London. 

The blockbuster therapy, which is being jointly developed and commercialized by AstraZeneca and Merck in a global strategic oncology collaboration struck in 2017, also met its key secondary endpoint, reducing the risk of distant disease recurrence or death by 43%. 

“New results for LYNPARZA® (olaparib) and IMFINZI® (durvalumab) continue to validate our strategy of treating cancer early in settings with curative intent, and data for CALQUENCE deliver on our commitment to improve the patient experience by demonstrating efficacy with safe, tolerable medicines,” said Dave Fredrickson, executive vice president of AstraZeneca’s oncology  business unit, prior to the conference.

On Monday, AstraZeneca will present final data from its ELEVATE-RR Phase III trial of Bruton’s tyrosine kinase (BTK) inhibitor, CALQUENCE® (acalabrutinib) in adults with previously treated chronic lymphocytic leukemia (CLL) at high risk for progression. In comparison with Imbruvica (ibrutinib), Calquence demonstrated significantly lower atrial fibrillation, fewer cardiac events, and fewer discontinuations.

Calquence met its primary endpoint, showing progression-free survival (PFS) non-inferiority versus ibrutinib with a median PFS of 38.4 months in both arms. Patients treated with Calquence were 6.6 times less likely to develop all-grade atrial fibrillation compared with those treated with ibrutinib. (9.4% versus 16.0%).

Adverse events led to treatment discontinuation in 14.7% of patients on Calquence, while 21.3% discontinued treatment with ibrutinib.

“We do not presently know or understand why some BTK inhibitors might be more prone to triggering cardiac adverse events such as hypertension or atrial fibrillation. However, additional studies presented within the summer meetings demonstrate that second-generation BTK inhibitors have fewer cardiac adverse events,” Dr. Jeff Sharman, medical director of hematology research for US Oncology at the Willamette Valley Cancer Institute & Research Center, told BioSpace.

Sharman explained that B-cell receptor signaling, which is vital to the survival of chronic lymphocytic leukemia cells, is impeded by BTK inhibitors, resulting in reduced proliferation and increased cell death among the malignant cells. CLL is the most common form of adult-onset leukemia.

ELEVATE-RR is the first head-to-head Phase III trial of two Bruton’s tyrosine kinase inhibitors (TKIs) in CLL.  Calquence won U.S. Food and Drug Administration (FDA) approval in this indication, as well as for small lymphocytic lymphoma (SLL) in November 2022. 

“Our ambition is to develop treatments that can provide meaningful time to patients and ultimately that can lead to cure. Treating cancer early is one of the critical ways of making this happen,” said AstraZeneca SVP of Late Development Oncology R&D, Christian Massacesi on the panel discussion. 

https://www.biospace.com/article/astrazeneca-redefining-cancer-care-in-breast-cancer-leukemia-at-asco/

J&J backs out of $1.6bn blood cancer antibody alliance with Argenx

 Belgian biotech Argenx has lost its development partner for acute myeloid leukaemia antibody cusatuzumab, after Johnson & Johnson backed away from the alliance after two and a half years.

J&J’s Cilag unit – part of its Janssen pharma division – said this morning that it had decided not to continue the collaboration after a “review of all available cusatuzumab data and in consideration of the evolving standard of care for the treatment of…AML.”

J&J paid Argenx a hefty $300 million upfront to secure rights to cusatuzumab (also known as JNJ-4550) in December 2018, and also made a $200 million equity investment in the Belgian company as part of a deal that had a total value of $1.6 billion.

At the time, cusatuzumab was billed as an important new treatment candidate for AML and other haematological cancers like myelodysplastic syndrome (MDS). The antibody blocks CD70, an immune checkpoint, and is designed to kill malignant cells by activating the immune system against them.

Since then however the programme has generated some disappointing clinical results, including follow-up results from the phase 1/2 CULMINATE trial announced earlier this year.

The study paired cusatuzumab with chemotherapy azacitidine in people with newly-diagnosed AML who were not physically strong enough to handle intensive chemotherapy, the main first-line therapy for this type of cancer.

Initial results from CULMINATE reported in 2018 just as the partnership with J&J was announced revealed that in the phase 1 stage of the study cusatuzumab achieved an 83% response rate, with five patients testing negative for minimal residual disease (MRD) – pointing to a good chance of long-term benefit.

Fast forward to January, and data from the phase 2 stage of CULMINATE showed that the response rate had dropped to 40%, raising big questions about its efficacy.

Argenx said it was waiting for the results of a phase1b ELEVATE trial of the antibody with azacitidine and Roche/AbbVie’s Venclexta (venetoclax), and in an update today said that so far that trial has a 93% overall response rate, including 48% a complete remissions.

“We believe these interim data show that cusatuzumab could be meaningful to AML patients,” said the biotech’s chief executive Tim Van Hauwermeiren, adding: “We plan to evaluate all alternatives to advance cusatuzumab on behalf of the AML community.”

In a statement Janssen said it will work with Argenx to transition the cusatuzumab programme back, adding that patients currently enrolled in ongoing trials “will continue to be supported through treatment and follow-up.”

Argenx had received $25 million in milestones before J&J’s exit was announced. The company share’s price was 6% weaker in early trading today but avoided a big selloff, suggesting that investors had already dialled down the importance of cusatuzumab to the biotech.

While clearly a big disappointment, Argenx will draw comfort from the progress being made with its lead programme efgartigimod for autoimmune disease generalised myasthenia gravis (gMG), which has been filed for approval in the US and Japan.

https://pharmaphorum.com/news/jj-backs-out-of-1-6bn-blood-cancer-antibody-alliance-with-argenx/

Alzheimer’s approval a huge boost for Biogen, but not everyone will be celebrating

 Biopharma’s biggest event of the year has swung Biogen’s way. News of aducanumab’s approval sent drug stocks higher; that the FDA is comfortable with ruling against a largely negative advisory committee and has granted approval despite inconclusive clinical data confirms the US agency as one of biopharma’s firmest friends.

The FDA’s nod to the controversial dataset is an accelerated approval, with the requirement to conduct a further study. This is unlike to appease critics of the decision, however: the trial will take years to conduct and will likely prove tricky to recruit if patients are reluctant to risk getting a placebo.

That means either designing the trial without a control arm – which seems unlikely – or perhaps running it outside of the US. Either way, the FDA has previously placed little pressure on developers to get such confirmatory studies under way quickly, meaning Biogen will have many years of aducanumab revenues to look forward to.

Considering the investment that Biogen has made in Alzheimer’s, this will be relief to both executives and investors, who were no doubt bracing themselves for a huge write off in R&D costs. Evaluate Omnium estimates that running aducanumab’s clinical trials cost $1.63bn, although total expenditures are likely to be much higher.

A look at the estimated cost of clinical trials across the beta-amyloid MAb projects shows that developers have committed billions of dollars to this mechanism. With today’s news those costs start to look salvageable; Lilly shares jumped a huge 12% in response to the approval of aducanumab, which is now brand named Aduhelm.

Targeting amyloid beta: key projects and estimated costs
Project/indication	Company/status	Estimated total cost of registered clinical trials*
Approved
Aduhelm (aducanumab)	Biogen/Eisai - approved by FDA June 2021	$1.63bn
Still in development
Crenezumab	Roche/AC Immune - ph2 in PSEN1 E280A mutation carriers due 2022	$1.01bn
BAN2410 (lecanemab)	Biogen/Eisai - ph3 read out in early disease late 2022	$1.42bn
Gantenerumab	Roche - ph3 readouts in early disease settings due 2022	$2.27bn
Solanezumab	Lilly - ph3 readout in at-risk asymptomatic patients due 2023	$2.8bn
Abandoned
Bapineuzumab	Pfizer/J&J - abandoned 2013	$2.42bn
*Registered on clinicaltrials.gov. Note: Numbers for Lilly's donanemab under review; readouts based on primary completion date in clinicaltrials.gov. Source: Evaluate Omnium.

While many believed that the FDA was likely to grant approval, it was assumed that the label would at least restrict use to certain patients. Instead, the label simply states that Aduhelm is “for the treatment of Alzheimer’s disease”. This means that it is down to payers to ration the drug, which they will surely seek to do considering the minimal efficacy and toxicity burden – and what is likely to be a high price tag.

In a statement from Dr Patrizia Cavazzoni, the director of the agency’s CDER division, the FDA acknowledged that there remains uncertainty about Aduhelm’s benefit. But it seems clear that the agency maintained its belief in the drug, an opinion that first emerged in surprisingly positive briefing documents ahead of the advisory committee.

“In all studies in which it was evaluated … Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion. It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” Dr Cavazzoni said today.

By choosing to grant accelerated approval – which the advisory committee was not asked to consider – the FDA has managed to neatly sidestep the negative panel that followed those briefing documents. But it will not quiet those that believe Biogen should have been required to provide much stronger evidence of this drug’s benefits, versus its risks.

Still, the outcome of Aduhelm’s regulatory review was always going to be controversial, whatever the FDA decided. While many will be happy to see Alzheimer’s patients getting access to what Biogen claims is the first disease-modifying drug, others will be feeling very uncomfortable about the precedent that this decision sets, in Alzheimer’s and beyond.

https://www.evaluate.com/vantage/articles/news/policy-and-regulation/biogen-makes-history-alzheimers-approval

Biogen upped to Outperform from Market Perform by Cowen

 Target to $450 from $225

https://finviz.com/quote.ashx?t=biib

US COVID-19 vaccination rates drop to under 1 million a day

 With only 3 weeks left to President Joe Biden's July 4th goal of seeing 70% of all American adults with at least 1 dose of COVID-19 vaccine, national vaccination rates are dropping across the country to fewer than 1 million shots administered per day.

That's a decline of more than 70% from the national peak of 3.4 million shots per day administered in April, according to a Washington Post analysis.

The slowdown is nationwide, but states in the South and Midwest report plummeting numbers. In Alabama, only 4 people per 10,000 residents got vaccinated last week.

According to the analysis, 13 states have met Biden's goal, and another 15 states, and Washington D.C., have vaccinated well over 60% of their adult populations and are forecasted to meet the Fourth of July goal.

But in 15 states, about half of adults or fewer have received at least one dose, according to a New York Times analysis.

The slowdown in vaccination efforts could lead to a summer and fall surge of virus activity in states with low coverage, including many Southern states, some experts warned.

J&J vaccine demand ebbs

After an 11-day pause in April to investigate possible vaccine-related blood blots, demand and interest in the Johnson & Johnson one-dose COVID-19 vaccine dropped in the United States, and remains low.

Close to half of the 21 million doses produced for the United States remain unused, Reuters reports. During the last week of May, fewer than 650,000 Americans received the vaccine, which mean it represented about 5% of all vaccines administered that week.

The Johnson & Johnson vaccine was shown to be highly efficacious, but less so than the two mRNA vaccines authorized for use in the United States. Now a new study from the Centers for Disease Control and Prevention (CDC) shows those two vaccines reduce the risk of infection by 91% for fully vaccinated people.

The findings come from 4 weeks of additional data added to CDC's HEROES-RECOVER study of health care workers, first responders, frontline workers, and other essential workers.

A total of 3,975 participants self-administered nasal swabs for 17 consecutive weeks to gauge vaccines efficacy: After one dose of mRNA vaccine, risk of infection dropped to 81%, after full vaccination, protection increased to 91%.

"COVID-19 vaccines are a critical tool in overcoming this pandemic," said CDC Director Rochelle Walensky, MD, MPH, in a media statement.

"Findings from the extended timeframe of this study add to accumulating evidence that mRNA COVID-19 vaccines are effective and should prevent most infections — but that fully vaccinated people who still get COVID-19 are likely to have milder, shorter illness and appear to be less likely to spread the virus to others. These benefits are another important reason to get vaccinated."

US case counts continue to fall

The United States reported 5,395 new COVID-19 cases yesterday, and 251 deaths, according to the Johns Hopkins COVID-19 tracker. 

The CDC COVID Data Tracker shows 371,520,735 COVID-19 vaccine doses have been delivered in the US, and 301,368,578 have been administered, with 138,969,323 Americans fully vaccinated.

But less than 25% of Black Americans had received their first COVID-19 shot as of June 3, despite efforts to accelerate vaccination in minority communities, according to Politico. Vice President Kamala Harris has been tapped to lead a vaccination tour throughout the Southern United States in the coming ways in an effort to quell vaccine hesitancy among Black communities.

https://www.cidrap.umn.edu/news-perspective/2021/06/us-covid-19-vaccination-rates-drop-under-1-million-day

Why Clover Health Investments Fell 22% in May

 Shares of Clover Health Investments (NASDAQ:CLOV) fell 22% in May, according to data from S&P Global Market Intelligence. First-quarter 2021 earnings weren't good enough to offset short sellers betting against the stock after it was noted earlier this year the Medicare insurance technologist is under federal investigation for how it compensates physicians for using its software.

DATA BY YCHARTS.

It's not all bad news for Clover Health, though. The company said revenue was up 21% year over year in Q1 to a record $200 million. Its Medicare Advantage insurance membership was at 66,300 as of the end of March 2021, up 18% from a year ago, and management expects this figure to be 68,000 to 70,000 by the end of this year. More importantly, its new traditional Medicare insurance product is expected to have 70,000 to 100,000 members by the end of 2021. As a result, full-year revenue should be $810 million to $830 million, up 22% from 2020's results at the midpoint of guidance.

The figure that has really captured investor attention, though, is the losses Clover expects to incur as it tries to expand its tech-enhanced Medicare products. Adjusted earnings before interest, taxes, depreciation, and amortization (EBITDA) losses could be as much as $240 million this year, according to the company's latest outlook. 

Clover is not in a dire situation. The company was nearing breakeven when it was in the process of completing its go-public proceedings backed by former Facebook (NASDAQ:FB) executive Chamath Palihapitiya. It had over $720 million in cash and equivalents, and no debt on its books at the end of March -- enough liquidity to last at least a couple of years at the expected rate of loss this year. Though federal investigation into its practices is certainly worth keeping an eye on, no official accusations have been made from authorities as of this writing. 

The real story here is the long-term potential Clover has to disrupt and improve the healthcare and insurance industry. It certainly has the cash to make some real waves and has experienced some early success in its journey. With over one-third of shares outstanding sold short, the pessimism surrounding Clover might be way overblown. 

In the short term, expect this to be a very volatile stock as the bull and bear arguments jockey for position over Clover. Shares are down over 30% year to date but have rallied over 20% from their low point in mid-May. However, if you believe in the long-term potential of this health insurance disruptor, the main metrics to stay focused on are membership growth and the company's cash on hand.

https://www.fool.com/investing/2021/06/07/why-clover-health-investments-stock-fell-22-in-may/