, analysts at Clarivate, a London-based intelligence and research firm, identified seven experimental treatments in late-stage development that they expect to deliver annual sales of more $1 billion within five years.

They include treatments for common conditions such as Alzheimer’s disease and asthma to those for very rare diseases such as 

, which is characterized by a build-up of deposits of amyloid, a protein, in various organs.Transthyretin amyloidosis is less common among Americans of European descent, where it is estimated to affect one in 100,000 people, but cardiac form affects between 3% and 3.9% of African Americans.

Here are the seven treatments that are likely to achieve blockbuster status in the next five years according to Clarivate:

 (Mirati Therapeutics Inc and Zai Lab Limited). The “long-awaited, targeted treatment” will likely be the first such treatment option in patients with colorectal cancerwith the KRASG12C mutation, who historically have had very few treatment options. Clarivate said in a 

 (Roche and Chugai Pharmaceutical). For patients with diabetic macular edema (DME) or wet age-related macular degeneration (AMD), faricimab offers a potentially more convenient option as it will be administered less frequently, on average, than the standard of care, Clarivate said in its news release. “As the first bispecific antibody to launch in ophthalmology, it also has the potential to be more efficacious than current standard of care, although data so far indicate it is non-inferior to the standard of care,” said the release

 (Eli Lilly) .“In this underserved market, anti-Aβ MAbs lecanemab and donanemab are poised to follow on the heels of the U.S. FDA’s landmark accelerated approval of Aduhelm for the treatment of AD,” Clarivate said. Lecanemab and donanemab could offer differentiated clinical profiles, which may be bolstered by phase 3 results that are expected to be reported beginning in late 2022. “Data across clinical trials suggest that sufficient exposure to optimal doses of anti-Aβ MAb therapy could be clinically effective in early AD,” Clarivate said.

(Amgen and AstraZeneca). The medication is a “potential game changer” for patients with non-TH2 or TH2-low asthma whose asthma is not well-controlled with inhaled corticosteroids, the current standard of care, according to Clarivate. “If approved, it would be a first-in-class biologic for this patient population. Tezepelumab will likely be a first-line biologic for severe TH2-low asthma and a treatment option for patients with TH2-high asthma for whom existing therapies have been less successful,” Clarivate said.

(Eli Lilly). The drug offers indication-leading reductions in weight loss and improvements in glycemic control in a growing patient population, which has the potential to reduce the incidence of complications from type 2 diabetes. “A new treatment that can more effectively address both weight loss and glycemic control than existing treatments would potentially be of great benefit to patient outcomes,” Clarivate said.

 (Alnylam Pharmaceuticals). Not only does this drug enter a relatively underserved market overall, it also has more convenient dosing options than other transthyretin amyloidosis -specific drugs on the market, Clarivate said. “For a progressive disease with a lot of unmet need, this drug brings efficacy, a generally favorable safety profile, and improvements in delivery that will benefit patient quality of life,” said the Clarivate press release.

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Lecanemab and donanemab, monoclonal antibodies for Alzheimer’s, are on the list of drugs in late-stage development that Clarivate analysts will have annual sales of a $1 billion or more in the next five years. 

Analyst Report: These 7 Treatments Destined To Be Blockbusters Within 5 Years

So far this month, pharma makers raised prices on 644 prescription drugs by an average of 5.7%, according to 

from prescription savings service SingleCare.

“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 

The biggest price changes were seen in antiviral and antiasthmatic medications, Yacoub told 

January 2022 Drug Price Increases tracker

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

According to SingleCare, the largest price hikes included: Advanced Accelerator Application’s Luthera (lutetium Lu 177 dotatate) up $3,552; Ipsen Biopharmaceutical’s Somatuline Depot (lanreotide) up $3,078; Acrotech Biopharma’s Zevalin Y-90 (ibritumomab tiuxetan) up $2,531; Gemzyme’s Lemtrada (alemtuzumab) up $1,868; and Recordati Rare Diseases’ Signifor Lar (pasireotide) up $1,853.

Despite this year’s price hikes, drug prices rose much more steeply (10.6% on average) in last January. “The higher mark by drug manufacturers in January 2021 was likely because of market effects of the COVID-19 pandemic,” Yacoub told 

The 5% increase is in line with recent years, he added, particularly since many 

manufacturers promised to keep annual increases

“While the manufacturer cost doesn’t directly translate to what the consumer pays at the pharmacy counter, the bottom line is that most consumers should not expect a substantial change in the price of their prescriptions, especially for those filling generic medications,” Yacoub noted.

According to a recent SingleCare survey, nearly half (47%) of Americans said that they’ve either skipped a prescription or a refill in the past year because the price of the drug was too expensive.

More than 600 drugs had price increases this month

 Leqvio (inclisiran) injection to be used in conjunction with diet and maximally tolerated statin therapy to lower LDL cholesterol in adults with familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL cholesterol. HeFH is a hereditary gene mutation that interferes with a person’s ability to clear cholesterol. Patients with HeFH typically have LDL cholesterol levels at least twice as high as normal levels and have an increased risk of cardiovascular events, such as stroke, coronary artery disease, and heart attack. ASCVD refers to cholesterol plaque buildup in arteries, which can lead to life-threatening events, such as heart attack, stroke, and peripheral artery disease.

Novartis Resubmits Application for Inclisiran

Leqvio (pronounced leck-vee-oh), which was developed by Novartis, is the first small interfering RNA (siRNA) therapy FDA-approved to lower LDL cholesterol. It interferes with RNA in hepatocytes to decrease the production of PCSK9, a protein that can increase circulating LDL levels. As a result of decreased PCSK9 production, Leqvio helps lower LDL cholesterol levels.

Leqvio is injected subcutaneously every six months after giving two loading doses three months apart.

Three randomized, double-blinded, placebo-controlled clinical trials studied the effectiveness of Leqvio in over 3,000 adults with HeFH or clinical ASCVD who were taking maximally tolerated statin therapy and required additional lowering of LDL cholesterol. The effectiveness of Leqvio was assessed by measuring the percentage change in LDL cholesterol levels after 17 months of treatment. In 

, patients taking Leqvio had an average of 51% decrease in LDL levels. Patients in the Leqvio group in 

 had an average of 46% decrease in LDL levels. In 

, patients taking Leqvio had an average of 40% decrease in LDL cholesterol levels. In all three trials, patients in the placebo group saw an increase in LDL cholesterol levels between 1% and 8%.

 ICER Chief on Bempedoic Acid and Inclisiran: Don’t Repeat the PCSK9 Mistake

Leqvio (inclisiran) is the first small interfering RNA therapy approved to lower LDL cholesterol in certain adults at risk for life-threatening cardiovascular events.

FDA Approves First-in-Class Therapy to Lower LDL Cholesterol

Walmart and Sam’s Club pharmacies are ready to receive and dispense Paxlovid and Molnupiravir, antiviral medications to treat COVID-19, in certain areas.

 for Merck’s molnupiravir to treat mild-to-moderate COVID-19) in adults with positive results of direct SARS-CoV-2 viral testing who are at high risk for progression to severe COVID-19 and for those whom for alternative COVID-19 treatment options authorized by the FDA are not accessible or clinically appropriate, the agency said in a 

 was originally going to be a treatment flu, but researchers at the Emory Institute for Drug Development in Atlanta shifted gears and developed it as a treatment for COVID-19

A day before the EUA for molnupiravir, the agency issued an 

 for Pfizer’s Paxlovid (nirmatrelvir tablets and ritonavir tablets, co-packaged for oral use) to treat mild-to-moderate COVID-19 in adults and pediatric patients.

Both antivirals are available by prescription only. Last summer, the Biden administration announced a plan that involves plowing $3.2 billion into research of antivirals as treatments for COVID-19.

Paxlovid and Molnupiravir will only be available at certain Walmart and Sam’s Club locations in a limited number of states until more supply is available, Walmart said in a 

Walmart worked closely with the federal government and state health departments to select locations where states determined the treatment was needed most, according to the retailer.

“While initial medication supply is limited, Walmart and Sam’s Club pharmacies stand ready to help expand treatment access nationwide,” the company said.

“We are committed to working with our state and federal partners to provide access to new treatment options like authorized COVID-19 antiviral medications, as they become available,” said Kevin Host, senior vice president of pharmacy at Walmart. “This medication offers customers the option to recover at home and helps reduce the burden on our hospitals and communities.”

Customers and healthcare providers can go to 

 to find the nearest store or club that is carrying the medication and to send the electronic prescription.








But Paxlovid and molnupiravir will be available only at certain Walmart and Sam’s Club locations.









Walmart, Sam’s Club to Distribute COVID-19 Antivirals

Included in the 408-page proposed rule are provisions that would make substance abuse treatment centers eligible as essential community providers.

The Biden administration recently released the 

Notice of Benefit and Payment Parameters 2023 Proposed Rule

 that is designed to make health insurance coverage more accessible and affordable in 2023. “Today’s rule is part of the Biden-Harris Administration’s ongoing efforts to ensure an equitable health care system as we continue to make coverage more accessible and affordable,” said Health and Human Services Secretary Xavier Becerra in a 

Executive Order on Promoting Competition in the American Economy

, which emphasizes affordable health insurance. This is the Biden administration’s first full notice and generally applies to changes for the 2023 plan year, not 2022.

The goal of the proposed rule is to improve shopping for healthcare coverage, establish rules ensuring the public can access care, and advance health equity for individuals purchasing coverage on the ACA marketplaces.

All insurance companies selling coverage on the federal healthcare.gov exchange and on the state-based exchanges would be required to provide standardized plan options for every product network type, metal type, and plan classification in addition to any service area where the issuer will provide marketplace plans.

CMS also proposes to implement network adequacy rules, which would include important features such as distance to care and appointment wait times. Additionally, the proposed rule will help to provide healthcare for low-income and medically underserved consumers, specifically through essential community providers (ECPs). Insurers would be required to include 35% of available ECPs in their network for each plan’s service area. The proposed rule would also include substance use disorder treatment centers as eligible ECPs, partly in response to the opioid epidemic. In November 2021, the 

 showing an estimated 100,306 death from drug doses in the 12-month period ending in April 2021, an increase of 28.5% from the April 2019-April 2020 time period. The same announcement said that 75,673 of those deaths were from opioids, an increase of 35% from the year before

The proposed rule will also prohibit health insurance companies from discriminating based on sexual orientation and gender identity and will restore protection for covered services that were previously removed in 2020 to reduce healthcare disparities and increase access to care. Health insurance companies must also rely on evidence-based medicine for making clinical decisions as part of the plan design under the proposed rule requirements.

Katie Keith, J.D., M.P.H., who writes “Following the ACA” analyses for the 

’ Forefront blog, has posted three in-depth pieces about the rule. Full text access it free and available 

. Keith is the director of the Health Policy and the Law Initiative at the O’Neill Institute for National and Global Health Law at Georgetown University Law Center.

Proposed Rule Could Make Healthcare Coverage More Affordable and Accessible for Consumers

 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, estimates of the cost burden of Aduhelm have focused almost exclusively on the annual 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 a 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 will increase Medicare Part B spending on Aduhelm by additional 20%.

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 is 5.7 million factors would be eligible in an “upper bound estimate. 

Based on those estimates and a projections that 25% of those eligible would receive Aduhelm, the researchers estimated that Medicare spending could range from $7 billion per year, of which $1.4 billion would be for ancillary services, up to $37.4 billion, of which $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. They weren’t necessarily serious or symptomatic, but ARIAs are would likely to mean additional MRI scans and visits with neurologists. 

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 Likely To Add 20% to 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.

Researchers: Ancillary Services Likely To Add 20% to Medicare Spending on Aduhelm

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

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

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

Medication Safety Considerations for COVID-19 Treatment Paxlovid