 to restrict Medicare coverage of Aduhelm (aducanumab) to people enrolled in approved clinical trials would likely lead to fewer Alzheimer’s patients taking the drug and reduced Medicare expenditures.

Even so, the cost burden of Aduhelm worries payers. The discussion of the drug's cost has been almost exclusively on the price of the drug itself, which Biogen slashed in half late last year, from $56,000 to $28,200, in a bid to make the drug more palatable to payers. In November 2021, before Biogen announced the price cut, CMS announced a 14.5% increase in 2022 Medicare Part B premiums that was attributed, in part, to the added cost of covering Aduhelm.

., of UCLA argue in a research published in 

 yesterday that Aduhelm will result in spending on PET and MRI scans and other “ancillary” services beyond the cost of the drug itself. In their calculations, the cost of those ancillary services would  comprise 20% of the total estimated Medicare Part B spending associated with Aduhelm.

Prior to the CMS proposal that might restrict coverage to those enrolled in sanctioned clinical trials, Mafi and his colleagues calculated that 1.1 million people might be eligible for Part B coverage of Aduhelm in a “lower bound” estimate that assumes prescribers would stick to the criteria used in clinical trial. Their “upper bound” estimate of eligibility was 5.7 million people.  

Based on those estimates and a projection that just 25% of those eligible would receive Aduhelm, the researchers estimated that Medicare spending on Aduhelm could range from $7 billion per year, $1.4 billion of which would be for ancillary services, up to $37.4 billion, $7.5 billion would be for ancillary services.

Some of the ancillary services included in these calculations are PET scans ($2,300 per year per patient on average, counting  patient coinsurance), routine MRIs ($555), APO E serum testing ($100 per patient), and hospitalization for adverse events ($294). 

One of the important predicates for these calculations is that a large percentage (41% of those on the highest dose) of the patients in the pivotal clinical trials of Aduhelm developed 

 (ARIA) that are characterized by fluid retention and microhemorrhages in the brain. The ARIAs weren’t necessarily serious or symptomatic, but they would likely to mean additional MRI scans and visits with neurologists and, therefore, added expense.

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In a research letter published in JAMA Health Forum, researchers say most of the cost figures for Aduhelm have left out the additional MRI scans and other services that will be required because the drug is associated with the development of amyloid-related imaging abnormalities (ARIAs).

Researchers: Ancillary Services Would Comprise 20% of Medicare Spending on Aduhelm

N-nitrosodimethylamine (NDMA), a carcinogen, has been detected in metformin, before and that has led to recalls of a drug taken by millions to manage their type 2 diabetes.

In the first drug recall of 2022, Cranford, New Jersey-based Viona Pharmaceuticals is voluntarily recalling 23 lots of metformin hydrochloride extended-release tablets, USP 750 mg, at the consumer level. The pharma maker shipped the metformin nationwide to distributors.

Viona found an out of specification (OOS) result for NDMA in one lot of the product. “In an abundance of caution, the firm has decided to voluntarily recall 23 batches, which we have determined having a valid shelf life within the US market,” Viona said.

The metformin in question was manufactured by Cadila Healthcare Limited in Ahmedabad, India.

Despite the recall, patients who have received the impacted lots are advised to continue taking their medication and contact their physician for advice regarding an alternative treatment, Viona said.

“According to the FDA, it could be dangerous for patients with this serious condition to stop taking their metformin without first talking to their healthcare professionals,” Viona said.

The metformin recalls began in early 2020, when the FDA said its testing found “certain extended release metformin products contain NDMA above the acceptable level.”

At that time, five major pharmaceutical manufacturers recalled their extended-release metformin tablets. Apotex, Amneal, Teva Pharamceuticals and Marksans Pharma Limited were among those issuing recalls.

Then, later that year, several other pharma makers followed suit with major metformin recalls.

For example, in October 2020, Marksans Pharma Limited in India is expanded its earlier initiated recall in June to include an additional 76 lots of Metformin Hydrochloride Extended-Release Tablets, USP 500 mg and 750 mg to the consumer level.

Problems with N-nitrosodimethylamine (NDMA)-contaminated metformin were identified by the FDA in 2020. Viona Pharmaceuticals announced in earlier this month that it was recalling 23 lots of the popular diabetes medication.

In First 2022 Recall, Metformin Pulled Back Because of Carcinogenic NDMA

 Adbry (tralokinumab-ldrm) injection for the treatment of moderate-to-severe atopic dermatitis in adults whose condition is not controlled with prescription topical agents or when topical therapies are not advisable.

Adbry joins IL-4 receptor antagonist Dupixent (dupilumab) as the second biologic FDA-approved to treat atopic dermatitis. The FDA approved Dupixent in 2017. The approval of Adbry was announced on Dec. 28, 2021. The new treatment is expected to be available in pharmacies next month.

Atopic dermatitis, also called eczema, is a chronic inflammatory skin condition typically characterized by patches of red, dry, itchy, and scaly skin. Excessive scratching of lesions can cause the skin to break, which can lead to skin infections and other complications. Symptoms can significantly affect quality of life, causing sleep disruptions, anxiety, and depression in some cases. Interleukin (IL)-13 was recently identified as a culprit cytokine in inflammation, skin infection, and other symptoms associated with atopic dermatitis.

Adbry, which was developed by Leo Pharma, is a fully human monoclonal antibody that specifically binds to IL-13 and blocks its inflammatory effects. It is the first FDA-approved biologic that binds to and inhibits IL-13. Adbry is administered by subcutaneous injection and can be used with or without topical corticosteroids.

Adbry’s FDA approval was based on the results from three randomized, double-blind, phase III clinical trials. The 

 trials evaluated the safety and efficacy of Adbry in adults with moderate-to-severe atopic dermatitis. The 

 trial assessed the safety and efficacy of Adbry in combination with topical corticosteroids in adults with moderate-to-severe atopic dermatitis. Primary endpoints for all trials included clear or almost clear skin at week 16 based on Investigator’s Global Assessment (IGA) scores and at least 75% improvement in Eczema Area and Severity Index (EASI) at week 16. A higher percentage of patients taking Adbry alone or with topical corticosteroids met all endpoints at week 16 than those in the placebo groups, and the frequency of adverse effects was comparable to that of placebo in all trials.

Leo Pharma's Adbry (tralokinumab-ldrm) is the second, FDA-approved  biologic for atopic dermatitis. Dupixent (dupilumab) was the first.

Dupixent Has Company. The FDA Has Approved Another Biologic for the Treatment of Atopic Dermatitis.

The Centers for Medicare and Medicaid Service’s (CMS) 

 to only cover Biogen’s Aduhelm (aducanumab-avwa) with significant restrictions will greatly hamper sales of the controversial Alzheimer's treatment drug , according to an analyst.

Under the proposed rule, CMS would cover Aduhelm and other monoclonal antibodies for Alzheimer’s disease patients only if they are participating in approved clinical trials. That limitation could significantly limit access, said Rose Joachim, pharma analyst at GlobalData, in a 

“The Centers for Medicare & Medicaid Services (CMS) proposes to cover FDA approved monoclonal antibodies directed against amyloid for the treatment of Alzheimer’s disease (AD) under Coverage with Evidence Development (CED) in CMS approved randomized controlled trials…and in trials supported by the National Institutes of Health (NIH),” CMS said in the 

 about the proposed coverage decision. . “All trials must be conducted in a hospital-based outpatient setting.”

“CMS’s decision to limit Medicare reimbursement of anti-amyloid mAb products to AD patients participating in randomized controlled trials (RCTs) will significantly delay and limit patient access to these products in the near term, with Biogen’s Aduhelm likely bearing the brunt of these troubles,” Joachim said.

Based on Aduhelm’s modest uptake, as well as Biogen's decision to cut the price of the drug by half, GlobalData estimates Aduhelm’s  sales to reach $906.1 million in 2028— only a quarter of the sales GlobalData had previously forecast for that year.

Biogen executives are also concerned about the CMS decision, which denies “nearly all Medicare beneficiaries from accessing Aduhelm….as well as future amyloid-directed therapies,” Biogen said in a 

“It is imperative to change this draft decision to be aligned with reimbursement for other therapies for progressive diseases, where patients have immediate and equal access to medicines approved by the FDA,” Biogen said. “It is urgent to act. Thousands of patients progress each day from mild to moderate disease stages, where treatment may potentially no longer be an option.”

If CMS continues to require a RCT when it issues a final decision in April, it would likely take in excess of a year to begin enrolling patients, further delaying reimbursement for Medicare beneficiaries, Biogen said.

“It is also particularly concerning that this draft implies that some Medicare beneficiaries will receive a placebo instead of a treatment they are seeking,” the pharma maker added.

Aduhelm has been extremely controversial since its approval earlier this year. In July, some Blues plans 

 they were waiting on the CMS decision on Aduhelm before setting their coverage policies.

Despite Aduhelm’s first-to-market advantage, the months of controversy following the drug’s approval were a “major setback,” Joachim said. “While CMS’s preliminary decision is yet another blow for the drug, the guidance can still potentially change, with a final decision expected in April."

CMS has proposed covering the anti-amyloid treatment only if the person taking it is enrolled in a clinical trial.

Analyst: CMS Decision Will “Significantly Limit" Biogen’s Aduhelm

Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) received 

 for the FDA on Dec. 22, 2021 for the treatment of mild-to-moderate COVID-19 in adults and children 12 years and older weighing at least 40 kilograms (88 pounds) with positive results of direct SARS-CoV-2 testing who are at high risk of progression to severe disease.

Pfizer has begun distributing Paxlovid, but it is available in limited supply. According to HHS, 64,970 courses had been distributed as of Jan. 7, 2022.

Institute for Safe Medication Practices (ISMP)

 has issued important safety concerns regarding Paxlovid and recommendations for physicians and pharmacists when prescribing and dispensing the medication.

, the recommended dose of Paxlovid for patients with normal renal function or mild renal impairment (estimated glomerular filtration rate (eGFR) 

 60 to < 90 ml/min) is 300 milligrams of nirmatrelvir (two, 150 mg tablets) with 100 milligrams ritonavir (one 100 mg tablet). Additionally, all 3 tablets must be taken together orally twice daily for five days. 

Patients with moderate renal impairment (eGFR 

 30 to < 60 ml/min) are supposed to take smaller doses: 150 mg of nirmatrelvir (one tablet) with 100 mg ritonavir (one tablet) taken together twice daily for five days. And patients with severe renal impairment (eGFR < 30 ml/min) are supposed to avoid Paxlovid altogether.

 to remove one of the nirmatrelvir tablets for both the morning and evening doses from each blister card and cover the empty blisters with pre-printed moderate renal impairment dosing instructions on all five cards with manufacturer-supplied stickers prior to dispensing Paxlovid. Pharmacists are also supposed to educate patients with moderate renal impairment that the packaging was altered to reflect the dosing changes. 

 to obtain additional stickers. Pharmacies should ensure that their staff are educated about these essential steps. Additionally, prescribers should ensure that the appropriate dosing is on all Paxlovid prescriptions for patients with moderate renal impairment. 

There are also drug interactions to be aware of with Paxlovid because it is an inhibitor of CYP3A, and it is critical for pharmacists to educate prescribers and patients about these since they can result in decreased Paxlovid efficacy or toxicity of the patient’s other therapies. Paxlovid treatment is contraindicated with the following medications:

Alpha1-adrenoreceptor antagonist: alfuzosin

Antiarrhythmics: amiodarone, dronedarone, flecainide, propafenone, quinidine

Antipsychotics: lurasidone, pimozide, clozapine

Ergot derivatives: dihydroergotamine, ergotamine, methylergonovine

PDE5 inhibitor: sildenafil (Revatio) for pulmonary arterial hypertension

Sedative/hypnotics: triazolam, oral midazolam

Anticonvulsants: carbamazepine, phenobarbital, phenytoin

Smaller doses are recommended for people with moderate renal impairment and the treatment should not be taken by people with serious kidney disease. There are also drug interactions to be aware of because Paxlovid is an inhibitor of CYP3A.

Medication Safety Considerations for COVID-19 Treatment Paxlovid

A few weeks after Mark Cuban Cost Plus Drug Company established its own pharmacy benefit manager (PBM), the company launched its online pharmacy.

Both the PBM and the online pharmacy are designed to “help shield consumers from inflated drug prices,” the company said in a news release.

Cuban is owner of the Dallas Mavericks, an NBA basketball team, and one of the featured investors on Shark Tank reality television series. Forbes magazine listed his net worth at $4.5 billion and ranked him 247th in its list of the 400 wealthiest Americans.

Cuban’s company is just the latest entry in the online pharmacy space. The number of online pharmacy services, including Amazon Pharmacy, have surged in recent years. And iHealthcareAnalyst projects the global market for internet pharmacies

predicted to attain to reach $191.2 billion by 2027, driven by rising personal disposable income, lower prices, and a surge in internet penetration.

As a registered pharmaceutical wholesaler, it can “bypass middlemen and outrageous markups,” the company said in a press release. The pharmacy's prices reflect actual manufacturer prices plus a flat 15% margin and pharmacist fee.

In addition, the company does not accept insurance and is a cash pay-only venture. The press release says that Cuban’s company “refuses to pay spread prices to third-party PBMs in order to be allowed to process insurance claims.”

This model means that patients can immediately purchase a broad array of medications at prices often less than what most insurance plans' deductible and copay requirements would total, the press release says

"We will do whatever it takes to get affordable pharmaceuticals to patients," said 

, the CEO, said in the press release. "The markup on potentially lifesaving drugs that people depend on is a problem that can't be ignored. It is imperative that we take action and help expand access to these medications for those who need them most.”

According to a September 2021 Gallup poll, 18 million Americans were recently unable to pay for at least one prescription medication for their household due to rising costs, and 1 in 10 Americans have skipped doses to save money, the press release said.

Cuban’s Mark Cuban Cost Plus Drug Company entered the PBM industry to serve companies providing prescription coverage in their employee benefit plans. His PBM has pledged to be "radically transparent" in its own negotiations with drug companies as a PBM, “revealing the true costs it pays for drugs and eliminating spread pricing and misaligned rebate incentives.”

The company plans to integrate its pharmacy and wholesaler with its PBM, so any company that uses its PBM will have access to wholesale pricing through its online pharmacy.

"There are numerous bad actors in the pharmaceutical supply chain preventing patients from getting affordable medicines," Oshmyansky said in the press release. "The only way to ensure affordable prices get through is to vertically integrate."

The company joins the wide array of online pharmacy services, such as Amazon Pharmacy, that have popped up in recent years. Cuban has also launched a namesake PBM.

Mark Cuban Cost Plus Drug Company Launches Online Pharmacy, PBM

The FDA has added two new pediatric indications for Xarelto (rivaroxaban). The regulatory agency’s decision in late December 2021 makes Xarelto the first FDA-approved direct oral anticoagulant (DOAC) for prevention venous thromboembolism (VTE) in patients ages 2 years and older with congenital heart disease after undergoing the Fontan procedure.

The FDA also gave the go-ahead for Xarelto as a treatment of VTE and to reduce the risk of recurring VTE in patients from birth to less than 18 years of age after receiving at least 5 days of initial parenteral anticoagulation therapy. 

Xarelto is the only DOAC available in an oral suspension, which facilitates pediatric weight-based dosing.

The Fontan procedure is a heart surgery performed in pediatric patients with a single functional heart ventricle. The procedure allows blood to flow directly from the heart into the lungs and leaves the functioning ventricle open to pump blood to the rest of the body.

Thrombosis is one of the most common complications associated with the Fontan procedure, and up to 25% of these thromboembolic events can be fatal.

Xarelto, developed by Janssen Pharmaceuticals, is a selective factor Xa inhibitor that directly binds to factor Xa to prevent thrombin formation. Some of its other indications are as a treatment for pulmonary embolism, prophylaxis of venous thromboembolism and risk reduction of major thrombotic vascular events in people with peripheral artery disease.

The approval of the new indications was based on results from two Phase 3 trials. The 

 study enrolled 112 children ages 2 to 8 years with single ventricular function and who had undergone the Fontan procedure within four months before trial enrollment. Participants taking Xarelto had fewer thromboembolic events than those taking aspirin, although results were not statistically significant. Both groups had similar rates of adverse events. The 

 study enrolled 500 children ages birth to 17 years with previously diagnosed VTE and who had begun parenteral anticoagulation treatment. After 3 months, a smaller percentage of children taking Xarelto showed signs of recurrent VTE versus participants using standard anticoagulation therapy.

The Janssen drug is the only DOAC available in an oral suspension, which facilitates pediatric weight-based dosing.

Xarelto Becomes the First DOAC FDA-Approved for Use in Pediatric Patients After Fontan Procedure

United States healthcare spending rose 9.7% in 2020, while medication spending is increasing by more than 18%, according to two separate reports.

The average price of branded drugs in the U.S. has increased by a significant 18.3% per year, based on the average over the past five years, according to 

“While drug list prices have only been increasing in the U.S., major markets in the rest of the world are seeing declines,” said Floriane Reinaud, MSc, research and analysis director at GlobalData. Japan, for example, saw drug prices decline by more than 9% while Germany declined by around 7.5%.

Plus, in early January, prescription savings service SingleCare reported that 

 on 644 prescription drugs by an average of 5.7%.

“We’ve already seen hundreds of prescription medications that will be more expensive in 2022, with the majority being brand drugs, and the most expensive changes being for specialty medications,” said Ramzi Yacoub, Pharm.D., the chief pharmacy officer for SingleCare, in a 

January 2022 Drug Price Increases tracker

 identified a similar trend in prices: 517 drugs increase in price by an average of 5%.

As governments in many countries cut drug prices, the pharmaceutical industry “is trying to compensate for revenue loss by increasing prices in the few countries where they are regulated by market forces — including the US,” Reinaud said.

However, the price increases are experienced at the published list level and, at the discount level, there are other trends that have been observed where drug prices are not increasing at the same level, Reinaud added.

“With this in mind, GlobalData still expects that prices will continue to rise in the U.S., at least at the list price level, while more competitive bidding dynamics will ensure that discounted net prices experience different trends,” Reinaud said.

Meanwhile, U.S. healthcare spending increased 9.7% in 2020 to reach $4.1 trillion, a much faster rate than the 4.3 percent increase seen in 2019, according to a new Health Affairs 

Health Affairs attributes the 2020 hike to a 36% increase in federal expenditures — primarily in response to the COVID-19 pandemic.

“At the same time, gross domestic product declined 2.2% and the share of the economy devoted to health care spending spiked, reaching 19.7%,” Health Affairs said.

United States healthcare spending rose 9.7% in 2020, while medication spending is increasing by more than 18%.

US Drug Prices, Healthcare Spending Soars

 has purchased one billion at-home COVID-19 rapid tests, and Americans can order them for free with a kick-off date beginning today.

The site is active now and appears to be working.

There will be 500 million tests available through the initial ordering process. Individuals can order their tests online at 

, and the Administration says they will start shipping them within 7-12 days of ordering. 

The website went live last week but the ordering function was not scheduled to start working till tomorrow. The administration apparently decided switch it on sooner than the announced start time.

Shipping is free, and there is no need to enter credit card information. The initial program permits the ordering of four free tests per household. The White House also says that a call line will also be launched so those without access to the internet will be able to place orders. 

The administration has also pledged to prioritize processing testing orders to communities experiencing the highest COVID-19 cases and mortality as part of a commitment to take into account health inequities and the disproportionate impact of COVID-19. The administration announcement about the testing program says it will work with “local organizations with deep experience serving communities of color, people living with disabilities, and other high-risk communities to serve as navigators, raise awareness about the program, and help people submit requests.”

Increasing the availability of at home tests comes at a critical time when COVID-19 transmission and hospitalizations are high, with the omicron variant accounting for approximately 

 of cases in the United States according to the latest CDC data. The administration also 

 that private health insurance companies are required to cover at-home COVID-19 tests for free starting Jan. 15, 2022. It has also made an additional 10 million tests available to schools nationwide. Private insurers are required to cover eight at-home tests per covered individual per month. However, that requirement leaves out uninsured Americans and those covered by Medicare. 

With the high demand of COVID-19 tests and limited availability through retailers, the launch of free tests through the Biden Administration’s efforts may help many families across the nation. However, a variety of issues may arise. 

Will the website crash  as millions, maybe even tens of millions, order tests? (So far, so good, today.) 

Will the wait times on the call lines be long? 

The tests will be shipped via the United States Postal Service. Will the postal service be capable of reliably delivering the tests? 

, there are approximately 332 million individuals residing in the U.S. Will there be enough tests? 

Will the people who need tests be able to get them? 

The answers to these and many more questions will become apparent over the next few days and weeks as the administration rolls out an unprecedented effort to have people test themselves and family members for a disease.

Free At-Home Rapid COVID-19 Tests Available To Order Today, A Day Earlier Than Scheduled

The FDA okayed two Janus kinase 1 (JAK1) JAK inhibitors January 14 the for atopic dermatitis (eczema).

AbbVie's Rinvoq (upadacitinib) treats moderate to severe atopic dermatitis (AD) in adults and children 12 years of age and older whose disease did not respond to previous treatment and is not well controlled with other pills or injections, or when use of other pills or injections is not recommended, AbbVie said in a 

Pfizer’s Cibinqo (abrocitinib) treats adults living with refractory, moderate-to-severe atopic dermatitis whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies is inadvisable, the pharma maker said in a 

“The reality for patients living with chronic inflammatory skin disease such as moderate-to-severe atopic dermatitis is that many experience debilitating symptoms that are not managed by current treatment options,” said Jonathan Silverberg, M.D., Ph.D., with the Department of Dermatology at The George Washington University School of Medicine and Health Sciences.

The approval of Cibinqo “will provide an important new oral option that could help those who have yet to find relief,” Silverberg added.

FDA’s approval of the medication was based on results of five clinical trials from a large-scale clinical trial program of more than 1,600 patients. Across the trials, Cibinqo demonstrated a consistent safety profile and profound improvements in skin clearance, extent of disease, and severity, as well as rapid improvement in itch after two weeks, for some people living with AD versus placebo.

In addition, a higher proportion of subjects treated with Cibinqo in two monotherapy trials achieved improvement in itching at week 12 compared to placebo, Pfizer said.

Meanwhile, FDA’s approval of Rinvoq is supported by efficacy and safety data from one of the largest registrational Phase 3 programs for atopic dermatitis with more than 2,500 patients evaluated across three studies, AbbVie said.

Across the three atopic dermatitis pivotal studies, Rinvoq (15 mg and 30 mg, once daily) monotherapy and with topical corticosteroids met all primary and secondary endpoints at week 16, with some patients achieving higher levels of skin clearance (EASI 90 and 100), according to AbbVie.

“In all three studies, a significant improvement in itch (Worst Pruritus NRS ≥4) was observed as early as week one, compared to placebo,” the pharma maker added.

"Despite available therapies, many people with moderate to severe atopic dermatitis are caught in an endless cycle of itching and scratching," said Emma Guttman-Yassky, M.D., Ph.D., Waldman professor and system chair of dermatology at the Icahn School of Medicine at Mount Sinai in New York City.

"In clinical trials, upadacitinib showed a robust response across skin and itch symptoms that may help evolve treatment goals for those who have not achieved adequate control of their disease,” Guttman-Yassky said. “And as an oral pill with two dose strengths, upadacitinib is a welcome addition to the toolbox of clinicians who are striving to make a significant difference for their patients with moderate to severe atopic dermatitis.”

The FDA okayed two Janus kinase 1 (JAK1) JAK inhibitors January 14 the for atopic dermatitis: Cibinqo and Rinvoq.

Mark Cuban Cost Plus Drug Company Launches Online Pharmacy, PBM

Xarelto Becomes the First DOAC FDA-Approved for Use in Pediatric Patients After Fontan Procedure

US Drug Prices, Healthcare Spending Soars

Free At-Home Rapid COVID-19 Tests Available To Order Today, A Day Earlier Than Scheduled

FDA Clears Two JAK 1 Inhibitors for Atopic Dermatitis