Denise Myshko

 Saphnelo (anifrolumab-fnia) for the treatment of adult patients with moderate-to-severe systemic lupus erythematosus (SLE) who are receiving standard therapy.

The agency's OK marks the first regulatory approval for a type I interferon (type I IFN) receptor antagonist and the first new treatment approved for SLE in more than decade.  

The FDA's approval is based on efficacy and safety data from several clinical trials, including two phase 3 trials and one phase 2 trial. In those trials, more patients treated with Saphnelo compared with those treated with a placebo were more likely to experience a reduction in overall disease activity across organ systems — including skin and joints — and achieved sustained reduction in oral corticosteroid use. In the trials. The trials were designed so that both the Saphnelo and the placebo groups were also treated with standard therapy.

Results from the TULIP-2 phase 3 trial were published in 

 in January 2020, results from the TULIP-1 phase 3 trial were published in 

 in December 2019, and results from the MUSE phase 2 trial were published in 

“Our treatment goals in systemic lupus erythematosus are to reduce disease activity, prevent organ damage from either the illness itself or the medications, especially steroids, and improve one’s quality of life,” 

, M.D., chief of the division of rheumatology at Northwell Health in New York, said in a 

. “Today’s approval of anifrolumab represents a big step forward for the entire lupus community. Physicians will now be able to offer an effective new treatment that has produced significant improvements in overall disease activity, while reducing corticosteroid use.”

 that 1.5 million Americans, and at least five million people worldwide, have a form of lupus. About 90% of the people living with lupus are women. The disease typically first occurs between ages of 15 and 44. 

Articles

This is the first new approval for lupus in a decade.

FDA Approves AstraZeneca Lupus Drug

 the Clozapine Risk Evaluation and Mitigation Strategy (REMS). Starting November 15, 2021, pharmacies that dispense clozapine will now need to obtain a pre-dispense authorization that can be accessed on the Clozapine REMS website (

) or the Clozapine REMS Contact Center (888-586-0758). They will no longer be able to use the current system, which is called the “switch system,” for verification.

Dispensing pharmacies, as well as wholesalers and distributors, will also need to recertify or re-enroll in the program, which can be done on the website beginning August 16, 2021.

Health care professionals prescribing clozapine will need to re-enroll all patients that are currently prescribed clozapine into the new Clozapine REMS. Physicians can now submit Patient Status Forms monthly, but there is a new form that is being used to document the absolute neutrophil count (ANC) results, monitoring frequency, and appropriateness to continue treatment.

Clozapine, including generics and branded therapies (Clozaril, Fazaclo ODT, Versacloz), is an atypical antipsychotic medicine used to treat schizophrenia symptoms that are not controlled with standard antipsychotic drugs. The drug is also used in patients with recurrent suicidal behavior associated with schizophrenia or schizoaffective disorder.

Clozapine, however, is associated with neutropenia, which can lead to serious and fatal infections.

The Clozapine REMS program was originally approved in September 2015 to monitor patients taking any of the clozapine products. Before this, each manufacturer operated separate monitoring programs.

Pharmacies will need to obtain pre-dispense authorization for clozapine.

FDA Updates Clozapine REMS Program

 to safety labeling for Piqray (alpelisib), Novartis’ therapy for patients with advanced or metastatic breast cancer, saying there have been some fatal cases of ketoacidosis in the postmarket setting.

The Warnings and Precautions section of the label, under hyperglycemia, now reads: “Severe hyperglycemia, 

in some cases associated with hyperglycemic hyperosmolar non-ketotic syndrome (HHNKS)

 or ketoacidosis has occurred in patients treated with PIQRAY. 

Some fatal cases of ketoacidosis have occurred in the postmarketing setting 

…” (Additions/changes are in italics.)

HHNKS is a serious complication of type 2 diabetes resulting from high blood glucose levels, which can result in a coma or seizures. Ketoacidosis is a serious complication of diabetes that occurs when liver metabolizes fat for fuel, resulting in high levels of ketones, a byproduct of that process.  

 Piqray in 2019 for use in combination with Faslodex (fulvestrant) for postmenopausal women, and men, with HR+/HER2- PIK3CA-mutated advanced or metastatic breast cancer following progression on or after an endocrine-based regimen.

A Novartis spokesperson said the company continues to learn more about the therapy as additional patients are treated. In the postmarketing setting, it is a regulatory requirement to continue to collect real-world safety data.

This process showed increased severity of an already known adverse reaction ketoacidosis, which triggered the prescribing Information update, the spokesperson said in an email. “At Novartis, patient safety is our utmost priority. The updated guidance for additional safety monitoring is to help physicians appropriately manage potential serious side effects,” she said.

That guidance suggests that, in addition to monitoring HbA1C every three months, physicians monitor fasting glucose more frequently for the first few weeks of treatment in patients with high risk factors for hyperglycemia such as obesity, elevated fasting plasma glucose  and HbA1c levels, use of systemic corticosteroids, and those over the age of 75.

Piqray continues to demonstrate that it is an important treatment option to address the needs of about 40% of patients with HR+/HER2- advanced breast cancer whose tumors harbor a PIK3CA mutation, which is linked to a poorer prognosis in the metastatic setting, the spokesperson said.

Some fatal cases of ketoacidosis have occurred, and high-risk patients should be monitored when starting treatment.


Piqray’s Safety Label is Updated

There has been a rapid increase in the costs of oncology drugs, but often they are not priced based on the value they provide, according to Andrew Hertler, M.D., chief medical officer of New Century Health, a specialty care management company focused on oncology and cardiology in Brea, Calif.

The value of new oncology therapies comes from increasing survival and improving the quality of life for patients, but newer therapies only provide incremental benefit that comes with a high price tag. “In 2020 alone, the average prices of new drugs coming to market [were] between $100,000 and $200,000 a year, with some drugs costing as much as $400,000 for an individual dose,” he said in an interview with 

Competition from newly approved therapies in the same class hasn’t worked to lower the cost. “Prices go up about 10% a year at pricing that is determined by what the market will bear. Patients really don’t have an option, because they want to live. We don't really have a shock on the price,” Hertler said.

An example, he said, is the checkpoint inhibitor class. Merck’s Keytruda (pembrolizumab), the first checkpoint inhibitor that targets the PD-1/PD-L1 pathway, was seen as a breakthrough when it was approved in 2014 for advanced melanoma. Since that time, it has received additional approvals and is now approved for 30 indications, with the most 

 being for the treatment of patients with high-risk early-stage triple-negative breast cancer (TNBC) in combination with chemotherapy before surgery and then continued as a single agent after surgery.

Today, Keytruda has a wholesale acquisition

 of $10,067 when given every three weeks, compared with a monthly 

 of $8,725 when it was approved. Since then, several other PD-1 checkpoint inhibitors have become available, including Bristol Myers Squibb’s Opdivo (nivolumab), Genentech’s Tecentriq (atezolizumab), and Regeneron’s Libtayo (cemiplimab).

The newest innovations, the chimeric antigen receptor (CAR) T-cell therapies, have an even higher price tag, especially when the total cost of patient care is considered. In fact, the total cost of administering CAR T-cell therapies averaged more than $700,000, and in some cases exceeded $1 million, even though the wholesale acquisition cost of the treatment is $373,000, according to data from a recent real-world data 

Over two-and-a-half years, Prime investigators looked at 74 members of Blue Cross and Blue Shield plans who received Novartis’ Kymriah (tisagenlecleucel) or Kite Pharma’s Yescarta (axicabtagene ciloleucel for the treatment of B-cell lymphoma.

The cost for CAR-T medication alone was $527,000 on average, which was 74% of the total cost during the initial treatment period. However, 12% of patients with post–CAR-T events incurred more than $1 million for their total cost of care, including drug and other costs, such as infusion center visits or transplants.

A 2018 Institute for Clinical and Economic Review report estimated the cost-effectiveness of the two CAR-T therapies in B-cell cancers and suggested the therapies are priced in alignment with their clinical value, despite their high price. According to the report, the cost-effectiveness of both CAR-T therapies fell near or within commonly cited thresholds of $100,000 to $150,000 per quality-adjusted life years (QALY). Because ICER’s study only estimated total treatment cost, Prime’s real-world evidence is another barometer to consider when evaluating whether CAR-T’s pricing is in line with value.

“Realistically, there has to be a consensus solution for these high costs,” Hertler said. “What we can do as physicians is to follow the clinical pathways for any clinical situation for what is the highest value drug. To me, if a drug just isn't that good, we shouldn’t use it. We routinely see approved drugs with 1.4 months to 1.6 months improvement in progression free survival. For marginal drugs, we don’t have to put them on our pathways.”

Drugs that provide only incremental benefit may not be included on clinical pathways.


Denise Myshko

Articles

FDA Approves AstraZeneca Lupus Drug

FDA Updates Clozapine REMS Program

Piqray’s Safety Label is Updated

Specialty Pharmacies Grapple with Assessing Costs and Value of Oncology Therapies