 a supplemental biologics license application (sBLA) for the potential expanded use of Takeda’s Takhzyro (lanadelumab-flyo) to prevent attacks of hereditary angioedema (HAE) in pediatric patients 2 to <12 years of age. Currently, children with HAE under the age of 6 have no approved prophylaxis treatment. If approved, Takhzyro could potentially become the first treatment for this population. The FDA has granted priority review and indicated a decision is expected in the first half of 2023.

Takhzyro is currently approved in patients 12 years and older to prevent attacks of hereditary angioedema (HAE), a rare disease that cause recurrent episodes of swelling of the limbs, face, intestinal tract and airway. Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. On average, untreated individuals have an attack every one to two weeks, and most episodes last for about three to four days.

Hereditary angioedema is estimated to affect 1 in 50,000 people. Hereditary angioedema type I and type II is caused by mutations in the 

 gene. Type III is cause mutations of the 

“Unpredictable, debilitating and potentially life-threatening HAE swelling attacks can cause a physical and emotional toll on those living with this rare disorder; this is burdensome for young children and their caregivers,” Cheryl Schwartz, senior vice president, U.S. rare disease business unit at Takeda, said in a press release.

The sBLA is based on data from the SPRING study, a phase 3 trial for HAE patients under the age of 12. Study findings 

 in June 2022, indicated children ages 2 to <12 experienced 94.8% fewer hereditary angioedema attacks during treatment with Takhzyro over the 52-week treatment period compared with baseline. No deaths or serious treatment-emergent adverse events were reported during the study, and no patients withdrew from the study due to adverse events. The most commonly reported adverse event was injection site pain, and most were mild or moderate in severity. These results are consistent with the favorable efficacy and safety profile of Takhyzro observed in earlier studies with adult and adolescent patients.

Articles

The FDA is expected to make a decision on approval in this patient population in the first half of 2023.

FDA Accepts BLA for Takhzyro in Young Children with HAE

Denise Myshko is your editorial contact for the Formulary Watch. She joined Formulary Watch as editor is June 2021 from Oncology Live. Prior to that, she was managing editor of PharmaVOICE, a trade publication in the pharmaceutical industry. Email: dmyshko@mjhlifesciences.com

Medicare and Medicaid spent more than $18 billion from 2018 to 2021 for 18 drugs granted accelerated approval that have incomplete confirmatory trials past their original planned completion date, according to new 

 by the Office of Inspector General, the U.S. Department of Health and Human Services. The OIG estimated that Medicare Part B and Part D spent more than $14 billion, and Medicaid spending —for both fee-for-service and managed care— for these drugs was nearly $3.6 billion.

“For a variety of reasons, sponsors do not always complete trials promptly,” OIG officials said in a 

 “This can result in drugs staying on the market-and being administered to patients for years without the predicted clinical benefit being verified. And insurers — including Medicare and Medicaid — are paying billions for treatments that are not verified to have clinical benefit.”

OIG officials began this review after the accelerated approval of Biogen’s Aduhelm (aducanumab) to treat patients with Alzheimer’s disease. The approval in June 2021 was made after an advisory committee voted against approval. Biogen is currently recruiting patients for its confirmatory trial ENVISION, which is expected to be completed in October 2026.

OIG officials indicated this review stemmed from concern that the regulator’s oversight of accelerated approval was lax. Accelerated approvals often use surrogate endpoints that predict clinical benefit, but don’t measure clinical benefit. The pathway is meant to provide earlier access to drugs to treat serious diseases. Companies are required to conduct confirmatory trials to verify clinical benefit and to provide a timeline for completion.

Since the accelerated approval pathway began in 1992, 278 drug applications have been granted accelerated approval by the FDA’s Center for Drug Evaluation and Research (CDER). Of these applications, 104 have incomplete confirmatory trials. Of those 104, 34% (35 of 104) have at least one trial past its original planned completion date. Additionally, 13% of all accelerated approval drug applications have been withdrawn, half of which were withdrawn since January 2021.

Four drug applications have confirmatory trials that are significantly late — ranging from more than five years to nearly 12 years past their original completion dates. OIG researchers found that of these four drugs that were significantly late with confirmatory trials, Proamatine (midodrine hydrochloride) had the highest Medicare Part D estimated spending at $142 million and Makena (hydroxyprogesterone caproate) had the highest estimated Medicaid spending, nearly $700 million.

Proamatine was given accelerated approval in 1996 to treat postural hypotension, and the FDA attempted to withdraw the application in 2010. Although the original sponsor no longer markets the product, generics are available even though a complete picture of risk and benefits doesn’t exist. OIG researchers speculate that the generic competition and the fact that the brand is no longer on the market may have decreased the sponsor’s incentive to complete confirmatory trials.

Makena was granted accelerated approved in 2011 to reduce the risk of preterm birth. It was developed by Amag Pharmaceuticals, now a subsidiary of Covis Pharma. The regulatory agency in 2020 began the process of removing Makena from the market, but the process can be lengthy if a manufacturer disagrees. An FDA 

 is scheduled for Oct. 17, 2022 to Oct. 19, 2022, to discuss the withdraw accelerated approval of Makena and whether available evidence demonstrates that Makena is effective for its approved indication.

Medicare and Medicaid spent more than $18 billion on drugs without verified clinical benefit.



OIG: One-third of Accelerated Approvals have Delayed Confirmatory Trials

Mark Cuban CostPlus Drug Company has added 12 new products and lowered the price of 39 additional medications. This follows an announcement in August where the company added 13 products and lowered the cost of 30 drugs.

Mark Cuban Cost Plus Drug Company launched in January 2022 to provide lower-cost generic medications. Medications are priced at cost with a 15% markup. The direct-to-consumer pharmacy now carries almost 1,000 medications.

Related:First PBM Integrates with Mark Cuban Cost Plus Drug Company

• Sirolimus 1 mg/mL (generic for Rapamune)

• Bupropion HCl SR 100 mg (generic for Wellbutrin SR)

• Glipizide Extended Release (ER) 10 mg (generic for Glucotrol XL)

• Hydroxyzine HCl 25mg (generic for Atarax)

• Ipratropium Bromide Nasal Spray 0.06% (generic for Atrovent)

• Ipratropium-Albuterol Solution 0.5-2.5 mg/3mL (generic for DuoNeb)

• Irbesartan 300 mg (generic for Avapro)

• Spironolactone / HCTZ 25 mg-25 mg (generic for Aldactazide)

• Triamcinolone Acetonide Lotion 0.025% 60 mL (generic for Kenalog)

• Triamcinolone Acetonide Cream 0.1% 454 gm (generic for Triderm)

• Triamcinolone Acetonide Ointment 0.1% 454 gm (generic for Aristocort A)

• Triamcinolone Acetonide Cream 0.1% 30 gm (generic for Triderm)

Some of the lower-price medications include:

• Albuterol 90 mcg Inhaler from $43.25 to $40.71 for 18 grams

• Atomoxetine HCl 25 mg Capsule from $21.90 to $15.60 for 90 capsules

• Atomoxetine HCl 60 mg Capsule from $36.30 to $23.70 for 90 capsules

• Atomoxetine HCl 80 mg Capsule from $43.50 to $25.50 for 90 capsules

• Atomoxetine HCl 100 mg Capsule from $59.70 to $28.20 for 90 capsules

• Estradiol Vaginal Estrogen Cream 0.01% from $54.32 to $34.28 for 42.5 grams

• Famotidine 40 mg Tablet from $10.20 to $5.70 for 90 tablets

• Fluticasone-Salmeterol 250 mcg/50 from $110.04 to $60.50 for 60 doses

• Norethindrone Acetate & Ethinyl Estradiol-1 mg/20mcg from $6.90 to $5.80 for 28 tablets

• Ondansetron ODT 4 mg Tablet from $26.40 to $20.10 for 90 tablets

• Rizatriptan Benzoate 10 mg Tablet from $82.20 to $71.40 for 90 tablets

• Venlafaxine 37.5 mg Tablet from $12.00 to $8.40 for 90 tablets

The online pharmacy has added 12 new products and lowered the costs of 39 medications.

Mark Cuban Pharmacy Adds Products, Lowers Costs on Others

The U.S. Department of Defense (DoD) has awarded a contract to SIGA Technologies to purchase up to $10.7 million of oral Tpoxx (tecovirimat), a treatment for monkeypox and smallpox.

“We are pleased to continue our growing relationship with DoD, which encompasses, among other things, providing oral Tpoxx to support the fight against orthopoxvirus risks such as smallpox and monkeypox and working closely with DoD on the continued development of the PEP indication for oral Tpoxx,” Phil Gomez, Ph.D., CEO of SIGA, said in a 

SIGA said $5.1 million of oral Tpoxx is targeted for delivery in 2022 and the remainder is subject to an option at the sole discretion of the DoD.

The Biomedical Advanced Research and Development Authority (BARDA), part of the office of the Administration for Strategic Preparedness and Response at the Department of Health and Human Services (HHS) also 

 it would buy $26 million worth of SIGA Technologies' IV TPoxx treatment courses. The IV form is an important option for those who are unable to swallow, SIGA said in a 

Additionally, SIGA has been collaborating with the DoD’s Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense (JPEO-CBRND) to develop the post-exposure prophylaxis indication for oral Tpoxx, and this work is supported by a separate development contract worth about $26 million.

issued an emergency use authorization (EUA) 

for Bavarian Nordic’s Jynneos monkeypox vaccine intradermal injection for people, including those under the age of 18, who are at high risk for monkeypox infection. This will increase the total number of doses available by up to five-fold, FDA said in a 

Jynneos, the modified vaccinia ankara (MVA) vaccine, was 

 as a subcutanous injection in 2019 for prevention of smallpox and monkeypox disease in adults 18 years of age and older determined to be at high risk for smallpox or monkeypox infection.

SIGA indicated that $5.1 million of oral Tpoxx is targeted for delivery in 2022. 

 U.S. to Buy up to $10.7 Million of Monkeypox Treatment

Beginning in 2023, Cigna will offer three new Medicare supplemental Prescription Drug Plans (PDPs) in all 50 states, the District of Columbia and Puerto Rico. The three plans include:

• Cigna Saver Rx: This economical plan includes low premiums, low copays and savings on generic drugs.

• Cigna Secure Rx: Available to serve customers with a low-income subsidy.

• Cigna Extra Rx: Provides a high level of coverage and savings on select insulins with copays as low as $0 at a preferred pharmacy.

All plans have $0 copay options for select medications purchased through preferred home delivery.

Additionally, Cigna will offer Medicare Advantage (MA) plans with enhanced features and benefits in 581 counties within 28 states. Cigna has also doubled the size of its MA provider network over the past two years, including significantly increasing the number of available specialists. Some enhanced features include: Cigna Healthy Today flex card that provides wellness incentives; a caregiver support program; companionship and support program; and Part B rebate plans.

Medicare Advantage customers can access care through a 24-hour nurse help line, $0 copay virtual healthcare for medical, behavioral health and physical therapy needs at in-network providers, home delivery of maintenance medications and over-the-counter supplies, and the MyCigna app.

Related: Humana Updates Medicare Pharmacy Benefits

Other companies including Humana have also updated their Medicare pharmacy benefits. In Medicare Part D, Human updates will include $0 copays for many commonly prescribed medications and a network of retail and mail-order pharmacies that offer preferred cost-sharing, including Walmart, Sam’s Club and several grocery chains. In addition, covered vaccines will be offered at $0 copay and covered insulins at no more than $35 for every one-month (up to a 30-day) supply. In partnership with Walmart, Humana will continue to offer the Humana Walmart Value Rx plan that features affordable copays and access to a preferred cost-sharing network.

Annual enrollment for Medicare begins Oct. 15, 2022, and continues through Dec. 7, 2022.

Cigna to Offer Three Stand-alone Medicare Drug Plans

 a supplemental new drug application for Alnylam Pharmaceuticals’ Oxlumo (lumasiran) to treat patients with primary hyperoxaluria type 1 (PH1), a rare and serious metabolic disease that often presents with kidney stones. It is caused by mutations in the AGXT gene that leads to the buildup of oxalate, which is filtered through the kidneys. The disease affects less than 5,000 people in the United States.

Oxlumo is an RNAi therapeutic administered via subcutaneous injection and is indicated to lower plasma oxalate levels and urinary oxalate levels in pediatric and adult patients. This approval adds lowering plasma oxalate levels to the indication. The therapy harnesses RNA interference, a natural cellular process of gene silencing.

“The significance of the label expansion of Oxlumo cannot be overstated, as this milestone provides crucial reassurance among a patient population with the highest unmet need, as well as their caregivers and loved ones, that Oxlumo is available in the US for patients living with PH1, including those with advanced disease,” Kim Hollander, executive director of the Oxalosis and Hyperoxaluria Foundation, said in a press release.

The approval is based on results of the ILLUMINATE-C phase 3 study in patients with severe renal impairment, including those on hemodialysis. In the trial, Oxlumo resulted in reductions in plasma oxalate levels and demonstrated an encouraging safety and tolerability profile in patients with compromised renal function, including those with kidney failure and undergoing treatment by hemodialysis. Elevated plasma oxalate levels result in systemic deposition of oxalate outside of the kidneys, potentially leading to bone fractures, cardiomyopathy, impaired erythropoiesis, vision loss, skin ulcers and other serious conditions.

The study assessed both dialysis-independent and -dependent patients. Patients in both cohorts had a reduction in plasma oxalate levels as early as month one. In the arm with six dialysis-independent patients, treatment with Oxlumo led to a 33% least squares mean reduction in plasma oxalate levels from baseline to month six. Least squares is a statistical method for estimating the true value of some quantity. In the arm with 15 hemodialysis-dependent patients, treatment with Oxlumo led to a 42% least squares mean reduction in plasma oxalate levels from baseline to month six.

There were two treatment discontinuations due to adverse events in the extension period of the study, neither of which was drug related. The most common adverse related to therapy was injection-site reaction reported in five of 21 patients (24%), which were all mild and transient.

The supplemental application also includes results from the open-label extensions of the ILLUMINATE-A and ILLUMINATE-B phase 3 studies of pediatric and adult patients with PH1. The label has correspondingly been updated to highlight the maintenance of sustained reductions in urinary oxalate through month 24 and month 12, respectively.

The FDA approved Oxlumo in November 2020 for the treatment of PH1 to lower urinary oxalate levels in pediatric and adult patients.

This approval for Oxlumo adds lowering plasma oxalate levels for patients with primary hyperoxaluria type 1, a rare and life-threatening metabolic disease.

FDA Approves Label Expansion for Oxlumo

Capital Blue Cross in Harrisburg, Pa., will become the first health plan to 

 with the Mark Cuban Cost Plus Drug Company. In 2023, Capital Blue Cross members will be able to use their insurance cards at Cost Plus Drugs. The insurer serves a 21-county region in Central Pennsylvania and the Lehigh Valley by offering health insurance products, services and technology solutions.

This agreement with marks the first time the Cost Plus Drug will accept insurance. Mark Cuban Cost Plus Drug Company launched in January 2022 offering cash-paying customers access to lower-cost generic medications. Medications are priced at cost with a 15% markup. The direct-to-consumer pharmacy now carries almost 1,000 medications.

“Working with a like-minded organization like Capital gives us more momentum to help people get the medications they need at costs they can afford,” Alex Oshmyansky, M.D., Ph.D., CEO of Mark Cuban Cost Plus Drug Company said in a press release.

Related: First PBM Integrates with Mark Cuban Cost Plus Drug Company

This announcement follows one last month in which Rightway became the first PBM to offer access to the generic drugs offered by Cost Plus Drug through its mobile app. Rightway’s pharmacists will identify members, such as those with chronic conditions, who may benefit from the service with Cost Plus Drugs and help them transfer their medications if they choose to do so.

In 2023, Capital Blue Cross members will be able to use their insurance cards at Mark Cuban Cost Plus Drugs. This is the first time the online pharmacy will accept insurance. 

Capital Blue Cross Teams up with Mark Cuban’s Pharmacy

Despite an increase in utilization of medications to treat mental health disorders between 2020 and 2021, EmpiRx Health’s drug spend for commercial payers actually decreased. Overall, behavioral health categories drove an increase of 9.4% in pharmacy claims year-over-year. EmpiRx Health saw a decrease of 4.7% in plan paid per utilizer.

The decrease, EmpiRx Health CEO Karthik Ganesh told 

 in an interview, is a result of the PBM’s value-based approach to healthcare.

“Everything that we do is in concert with the physician,” he said. “Trained pharmacists have critical conversations with the physician about clinically appropriate yet lower-cost alternatives. They help to optimize alternatives for that patient, presenting the clinician with a compelling case study or a case summary.”

Ganesh said the pharmacists are an extension of the patient’s care team. “They have an 88% engagement rate with physicians,” Ganesh said. “These results are directly correlated to our pharmacists being able to convince clinicians to go with a clinically appropriate yet lower-cost alternative.”

EmpiRx uses analytics and AI technology to create a tailored approach for managing a population of patients. Applying this approach to mental and behavioral health medication has led to a decreased drug spend. Specific to anti-depressants, while year-over-year utilization increased by 12%, EmpiRx saw a decrease in gross spend per claim by 1.8%.

Specific to attention deficit/hyperactivity disorder (ADHD), adults over the age of 26 have driven a consistent increase in treatment for more than three years, now accounting for 50% of all ADHD utilizers. Overall ADHD utilization increased by 20.2% year over year, countered by a 9.1% decrease in gross spend per claim.

Ganesh said EmpiRx’s patient population is diverse and mirrors the United States in terms of race, ethnicity, gender, and age, as well as demographic and social and economic factors.

EmpiRx has developed an AI that uses the Johns Hopkins ACG System, which is population health analytics software that uses diagnosis, pharmacy and lab data, and big data tools. The PBM then creates a risk profile to identify personal risk factors.

In 2019, the PBM has developed a complex care management model that includes mental health. The AI system identifies patients who are high risk, who have comorbidities, have called the company two or more times, have been prescribed an antidepressant or a history of opioid abuse to be part of the complex care model. This care model provides patients with a care coordinator to help them manage their care and medications.

EmpiRx Health CEO Karthik Ganesh discusses how the PBM was able to decrease mental health drug spending at a time when utilization is increasing.

EmpiRx Health Lowers Drug Spend in Mental Health

 additional data on Eiger BioPharmaceuticals’ request for emergency use authorization (EUA) of peginterferon lambda to treat patients with mild-to-moderate COVID-19, the pharma maker said it will not submit the EUA.

Following a pre-EUA information exchange with the FDA regarding the phase 3 TOGETHER study of peginterferon lambda for COVID-19, the agency indicated in September that it was not yet able to determine whether the criteria for the submission of an application and issuance of an EUA are likely to be met, Eiger said in a 

The company then submitted a pre-EUA meeting request to FDA, as well as additional morbidity and mortality outcomes data and analyses from the 

“This included further statistical modeling and efficacy analyses of the study's primary and secondary endpoints and long-term follow-up data that the company believes continue to support the initial positive topline outcomes reported in March,” Eiger said. “In response, FDA denied the request for a pre-EUA meeting.”

“Citing its concerns about the conduct of the 

 study, FDA concluded that any authorization request based on these data is unlikely to meet the statutory criteria for issuance of an EUA in the current context of the pandemic,” Eiger added.

However, given peginterferon lambda's mechanism of action and the ongoing need for improved COVID-19 therapeutics, the FDA suggested that Eiger consider requesting an end-of-phase 2 meeting to discuss a company-sponsored pivotal trial that could support an eventual biologics license application (BLA).

“While we are disappointed that the FDA will not consider an EUA application based on results generated from the 

 study, we continue to have strong conviction in the potential of peginterferon lambda to confer a meaningful benefit for patients with COVID-19 and other respiratory viral infections,” David Cory, president and CEO of Eiger, said in a 

. "COVID-19 related deaths remain alarmingly high around the globe, including in the United States where, according to recent data from the Centers for Disease Control and Prevention, about 400 people die every day from this disease.”

Eiger officials said they are evaluating next steps for this program in the United States, as well as ex-U.S. emergency use authorization pathways and strategic options for continued development of peginterferon lambda for COVID-19 and other respiratory viral infections.

Eiger licensed worldwide rights to peginterferon lambda, an investigational late-stage, first-in-class, type 3 interferon (IFN) that stimulates immune responses that are critical for the development of host protection during viral infections, from Bristol-Myers Squibb.

Eiger is also developing peginterferon lambda to treat hepatitis D (HDV) infection. Peginterferon lambda has been administered to more than 4,000 subjects in 28 clinical trials of hepatitis B, hepatitis C, hepatitis D, and COVID-19.

The FDA had indicated that it would not issue an emergency use authorization without additional data for peginterferon lambda to treat patients with mild-to-moderate COVID-19.

Eiger Will Not Submit EUA For COVID-19 Treatment

UnitedHealthcare is offering expanded access and lower prescription drug costs for some 2023 Medicare Advantage and prescription drug plans. The insurer that 99% of members in standard and Chronic Special Needs Plans (C-SNPs) will have stable or reduced premiums – including nearly 3.3 million members with a $0 premium – and all will have stable or improved core and prescription drug benefits.

Additionally, all Medicare Advantage members will see stable ancillary benefits, with 91% receiving better-than-ever ancillary benefits like dental, hearing, over-the-counter and prescription drug coverage. The Medicare Advantage formulary will have more drugs in tier 1 and move even more commonly used drugs to lower tiers, which target conditions such as cardiovascular disease, depression, osteoarthritis, glaucoma, and overactive bladder. 

(See table below for a list tier changes.)

More plans will lower tier 1 retail copays to $0, giving nearly all members in standard plans and Chronic Special Needs Plans (C-SNPs) free access to the most common adherence medications. And 100% of members will have $0 tier 1 and 2 copays through Optum Home Delivery, up from 93% in 2022. Additionally, 87% of members will have no Rx deductibles, up from 59% in 2022.

All members without Extra Help enrolled in C-SNPs will have access to insulin at $25 ($10 less than standard plans) in addition to diabetic supplies on tier 2, giving access to $0 copays for supplies when using home delivery. C-SNP members will also have access to eight medications on a lower drug tier that target cardiovascular disease.

UnitedHealthcare will continue to expand access to $0 copays on covered drugs to 96% of its members enrolled in Dual Special Needs Plan (D-SNP).

* updated to include table with tier changes

UnitedHealthcare is moving more drugs to the lower-cost tiers in its Medicare Advantage plans. Other plans will have $0 copays and insulin at a $25 copay.

FDA Approves Label Expansion for Oxlumo

Capital Blue Cross Teams up with Mark Cuban’s Pharmacy

EmpiRx Health Lowers Drug Spend in Mental Health

Eiger Will Not Submit EUA For COVID-19 Treatment

UPDATED: UnitedHealthcare Makes Formulary Changes for Medicare Plans