Author: Randy Chase

Some years ago, payers demanded that specialty pharmacies obtain accreditation to even be considered for inclusion in their specialty pharmacy networks. It was an effective blocking tactic…. for a while. As many specialty pharmacies obtained specialty pharmacy accreditation those wraskley payers upped the game by requiring two accreditations.  

Since then, accreditations have been offered for a host of other niche business segments including Mail Order, Long Term Care, and Infusion Pharmacy. Oh, and throw in ‘Distinctions’ in Oncology, and Rare and Orphan Diseases, and more. Piling on accreditations is a strong argument that the specialty pharmacy meets virtually any requirement a payer could throw at them. 

The article below is timely as it raises awareness of the need for yet another accreditation.   CMS is requiring a special accreditation for delivery of Infusion services resulting in infusion confusion. If your organization hasn’t already moved to obtain the new accreditation it is time to play catch up. You may have accreditation in Infusion Pharmacy….. but, that’s not what CMS is looking for. The new version targets the delivery of nursing services in the home.  Just look at it like chocolate and peanut butter. So, read the article to get a full picture or just call your accrediting company and have a discussion.  

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Home Infusion Therapy Accreditation Rolls Out

• Compliance a Must Under CMS Regulations

 By Gina ShawSpecialty Pharmacy Continuum FEBRUARY 23, 2021 — As of Jan. 1, 2021, home infusion providers are officially required by the Centers for Medicare & Medicaid Services (CMS) to obtain accreditation to bill Medicare Part B for home infusion therapy (HIT) services. To make that transition to compliance a success, providers need to consider a number of important factors, according to three organizations now offering the accreditation. 

The first is to know that Medicare HIT accreditation is not necessarily for everyone, noted Jon Pritchett, PharmD, the program director overseeing pharmacy programs for the Accreditation Commission for Health Care (ACHC). “Some places just focus on pediatric infusions, and Medicare may not be a significant part of what they do,” he explained. “But for organizations that have a heavy Medicare population and a lot of those medications are covered, then there’s a good return on investment for this accreditation.” 

It’s also important to know why HIT accreditation has gained traction. Historically…………CLICK HERE TO READ THE FULL ARTICLE

Almost ten years ago we started to raise the alarm of the threat that hospital-owned and operated specialty pharmacies pose to the Specialty Pharmacy (SP) industry given their ability to direct prescriptions ‘in house’. That trend has accelerated to the point where a large percentage of such systems are now in the business.

The article below is the first that I’ve seen that raises another red flag. This time it is a concern for the health systems, and it has everything to do with a practice that has gotten many a provider into hot water – self-referral.

The article points out that health systems that haven’t yet fully jumped into the Specialty Pharmacy pool are now contracting with outside entities to run their SP operations for them under contract. That kind of relationship can actually generate additional compliance issues and state and federal scrutiny particularly surrounding anti-kickback statutes, and how each ‘partner’ is reimbursed.

We learned in the recent merger of Shields Health and ExceleraRx, that they are promoting contract SP deals. Over the past decade they have helped most of the larger health systems open in-house SP operations. Smaller hospitals, however, are more likely to favor the contract vendor solution and wash their hands of day to day operational challenges. In that case the contract vendor would likely take on more responsibilities and, logically, get more compensation.

Regulators will focus on a number of factors to ensure that the arrangement between the health system and management company is compliant with key statutes. Read the article for a short list of red flags that could suggest a questionable contracting arrangements and consider the following excerpts.
“You can’t just have a management company coming in and taking over everything and giving the hospital a fee for this contractual arrangement.”
“If you can reduce costs, keep utilization low, improve patient outcomes and not be anti-competitive, then it should be a very good arrangement under the Anti-Kickback Statute.”

So, is the tsunami of hospitals and systems cannibalizing traditional specialty pharmacy ready to subside? Not likely…… just sayin’.

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Hospitals Contracting for Specialty Pharmacy Services Face Compliance Issues

By Gina Shaw, Specialty Pharmacy Continuum
As more and more health systems enter the specialty pharmacy space, many are turning to outside third-party entities to manage their on-site specialty pharmacies. Although the arrangements offer many benefits, those involved in the partnerships need to be ready for state and federal scrutiny surrounding anti-kickback statutes, reimbursement and other compliance issues that could derail these arrangements if not managed proactively.

In these partnerships, the pharmacies are still owned by the hospitals, but they’re managed by outside vendors with specific expertise in specialty pharmacy operations—such as Recept, Shields Health Solutions and Trellis Rx—in exchange for fees and, sometimes, a share of the profits.

“There are core competencies that come with running specialty pharmacies, and depending on what expertise a hospital or health system already has on board, the management companies can really help with those, including access to payor networks, access to limited distribution drugs and assistance with accreditation,” said Todd Nova, JD, an attorney with Hall, Render, Killian, Heath & Lyman, an Indianapolis-based firm specializing in health law.

But contracting with a third-party specialty pharmacy management company poses a set of legal and regulatory issues that hospital and health-system compliance departments will have to navigate, said John W. Jones Jr., JD, a partner in the Philadelphia-based firm of Troutman Pepper Hamilton Sanders LLP.

Anti-kickback regulations are a major focus for HHS OIG, he noted. The regulators have highlighted several areas of concern that would raise red flags suggesting a questionable contracting arrangement, he said:
The owner (the hospital or health system) expands into a related line of business, which is dependent on referrals from, or other business generated by, its existing business.
The hospital or health system neither operates the new business itself nor commits substantial financial, capital or human resources to the venture—in this case, a specialty pharmacy. Instead, it substantially contracts out virtually all of the new business.
The third-party contractor is an established provider of the same services as the new line of business and, absent the contract, would be a competitor, providing items and services in its own right, billing insurers and patients in its own name, and collecting reimbursement.
The owner and third-party contractor share in the economic benefit (the profits) of the business, in the economic benefit of the owner’s new business.
Payments to the third-party management company vary by the value or volume of business generated for the specialty pharmacy by the hospital.

Jones explained that the Department of Health and Human Services Office of Inspector General (OIG)…………….

CLICK HERE TO READ THE FULL ARTICLE

The FDA approved a new infused specialty therapy last week, Pepaxto (melphalan flufenamide) from Oncopeptides AB, for patients with relapsed or refractory multiple myeloma following four or more lines of therapy. It is the first anticancer peptide-drug conjugate approved by the FDA.

Multiple myeloma is a cancer of plasma cells, a type of white blood cell which produces antibodies to help fight infection. Multiple myeloma causes cancer cells to accumulate in the bone marrow.

Approximately 7 per 100,000 Americans per year are diagnosed with multiple myeloma, making it a rare disease. However, the number of patients diagnosed with multiple myeloma is growing and the number of cases diagnosed annually is expected to almost double in 20 years. The average age for diagnosis is 70 years of age, and there is currently no cure.

Pepaxto is administered intravenously over 30 minutes on Day 1 of each 28-day cycle until disease progression or until unacceptable toxicity. Pepaxto is administered in combination with dexamethasone 40 mg orally or intravenously on Days 1, 8, 15 and 22 of each cycle.

Pricing for Pepaxto has not yet been confirmed.

Oncopeptides will release Pepaxto in the U.S. this month. They also announced that the product will be available through both wholesalers and specialty pharmacies. They did not specify whether they will implement a specialty pharmacy limited distribution program for this infused product. Given the small US patient population an LD program is likely.

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FDA approves Oncopeptides’ PEPAXTO® ( melphalan flufenamide) for patients with relapsed or refractory multiple myeloma

STOCKHOLM, Feb. 26, 2021 /PRNewswire/ — Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO), a global biotech company focused on the development of therapies for difficult-to-treat hematological diseases, today announced that the U.S. Food and Drug Administration, FDA, has approved PEPAXTO® (melphalan flufenamide, also known as melflufen), in combination with dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

The product has been granted accelerated approval based on the phase 2 HORIZON study in relapsed or refractory multiple myeloma.

“The accelerated approval of PEPAXTO in the US is an important……….
Click here to access the full press release

The FDA approved a new infused therapy last week, Amondys 45 (casimersen)) from Sarepta Therapeutics, with an indication for Duchenne Muscular Dystrophy (DMD). Amondys is further limited to treat the 8% of Duchenne patients with the exon 45 skipping genetic mutation. It is administered weekly by IV infusion in the home or infusion center.

DMD is the most common type of muscular dystrophy. DMD is caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between 3 and 5 years of age and worsen over time. The disease often occurs in people without a known family history of the condition and primarily affects boys, but in rare cases it can affect girls. DMD occurs in about one of every 3,600 male infants worldwide. Since there are about 40,000 individuals with DMD in the US that translates into only ~3,200 candidates for the 8% that Amondys targets.

There are other dystrophin-gene-mutation, disease-modifying therapies for DMD on the market– Exondys 51 (skips dystrophin gene #51) and two that target gene #53, Vyondys 53 and Viltepso. All directly promote dystrophin production in the body.

People with DMD progressively lose the ability to perform activities independently and often require use of a wheelchair by their early teens. As the disease progresses, life-threatening heart and respiratory conditions can occur. Patients typically succumb to the disease in their 20s or 30s; however, disease severity and life expectancy vary.

Amondys 45 53’s price will be comparable to Vondys 53 and Exondys 51 (both are Sarepta therapies)….. neither of which is cheap. It is dosed based on weight. For example, a 50 lb. child would run a whopping $350,000 per year with older /larger patients costing upwards of $1 million annually.

All DMD products have been launched through limited distribution (direct-to-office / hospital/home infusion) using a specialty pharmacy. Since dosing is weekly home infusion will be common. We have been able to confirm that Sarepta has selected Orsini Specialty Pharmacy to support their limited distribution – direct-to-office (LD-DTO) program.

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FDA Approves Targeted Treatment for Rare Duchenne Muscular Dystrophy Mutation

February 25, 2021 — Today, the U.S. Food and Drug Administration granted approval for Amondys 45 (casimersen) injection for the treatment of Duchenne muscular dystrophy (DMD) in patients who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping The agency approved Amondys 45 based on an increase in dystrophin (a protein that helps keep muscle cells intact) production in skeletal muscle observed in patients treated with the therapy. This is the first FDA-approved targeted treatment for patients with this type of mutation. Approximately 8% of patients with DMD have a mutation that is amenable to exon 45 skipping.

“Developing drugs designed for patients with specific mutations is a critical part of personalized medicine,” said Eric Bastings, M.D., deputy director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Amondys 45 provides a targeted treatment option for Duchenne muscular dystrophy patients with this confirmed mutation.”

Amondys 45 was evaluated in a double-blind, placebo-controlled study in which 43 patients were randomized 2:1 to receive either intravenous Amondys 45 (30 mg/kg) or placebo. All patients were male, between 7 and 20 years of age, and had a genetically confirmed mutation of the DMD gene that is amenable to exon 45 skipping.

In the study, patients who received Amondys 45 showed a significantly greater increase in dystrophin protein levels from baseline to week 48 of treatment compared to those who received placebo.

The FDA has concluded that the data submitted by the applicant demonstrated an increase in dystrophin production that is reasonably likely to predict clinical benefit in patients with DMD who have a confirmed mutation of the dystrophin gene amenable to exon 45 skipping. A clinical benefit of the drug, including improved motor function, has not been established. In making this decision, the FDA considered the potential risks associated with the drug, the life-threatening and debilitating nature of the disease, and the lack of available therapy.

The most common side effects observed in DMD patients treated with Amondys 45 were upper respiratory tract infections, cough, fever, headache, joint pain and throat pain.

Although kidney toxicity was not observed in the Amondys 45 clinical studies, kidney toxicity was observed in the nonclinical studies. Kidney toxicity, including potentially fatal glomerulonephritis, has been observed after administration of some antisense oligonucleotides. Kidney function should be monitored in patients taking Amondys 45.

Amondys 45 was approved using the Accelerated Approval pathway, under which the FDA may approve drugs for serious conditions where there is unmet medical need and a drug is shown to have certain effects that are reasonably likely to predict a clinical benefit to patients. Further study is required to verify and describe anticipated clinical benefits of Amondys 45, and the sponsor is currently conducting an ongoing, double-blind, placebo-controlled, multicenter study designed to evaluate the safety and efficacy of Amondys 45 in ambulatory DMD patients.

The FDA granted this application Fast Track and Priority Review designations. Amondys 45 also received Orphan Drug designation, which provides incentives to assist and encourage the development of drugs for rare diseases.

The FDA is granting the approval to Sarepta Therapeutics, Inc.

Earlier this month the FDA approved another infused specialty therapy, Cosela (trilaciclib) from G1 Therapeutics. It is the first therapy in its class to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving certain types of chemotherapy for extensive-stage small cell lung cancer (when the cancer has spread beyond the lungs).

Cosela is to be used as a protective agent against bone marrow loss among adults before chemotherapy regimens that contain a platinum agent/etoposide or topotecan for extensive-stage small cell lung cancer. Previous treatments that address bone marrow injury have only attempted to remedy it after the fact.

The American Cancer Society estimates for all types of lung cancer in the United States for 2021 are:
~235,000 new cases of lung cancer (119,100 in men and 116,660 in women)
~131,000 deaths from lung cancer (69,410 in men and 62,470 in women)
Small Cell Lung Cancer represents ~20%+ of new cases or ~50,000 new cases annually

Cosela will hit the market at a wholesale acquisition cost of $1,471 per vial, and a full treatment will cost about $34,000 per patient on average.

Distribution details were not released by G1 Therapeutics. Given the fairly large eligible patient population and ‘relatively’ low price, it is unlikely that this new specialty therapy will be handled through specialty pharmacy distribution.

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FDA Approves Drug to Reduce Bone Marrow Suppression Caused by Chemotherapy
Drug Is Given Before Chemotherapy to Protect Bone Marrow Function

February 12, 2021 — Today, the U.S. Food and Drug Administration approved Cosela (trilaciclib) to reduce the frequency of chemotherapy-induced bone marrow suppression in adults receiving chemotherapy for extensive-stage small cell lung cancer. Cosela may help protect bone marrow cells from damage caused by chemotherapy by inhibiting cyclin- dependent kinase 4/6, a type of enzyme.

“For patients with extensive-stage small cell lung cancer, protecting bone marrow function may help make their chemotherapy safer and allow them to complete their course of treatment on time and according to plan,” said Albert Deisseroth, M.D., Ph.D., supervisory medical officer in the Division of Non-Malignant Hematology in the FDA’s Center for Drug Evaluation and Research. “Today’s approval of Cosela will give patients a treatment option that can reduce the occurrence of a common, harmful side effect of chemotherapy.”

Chemotherapy drugs are designed to kill cancer cells but can damage normal tissues as well. The bone marrow is particularly susceptible to chemotherapy damage. The bone marrow makes red blood cells, white blood cells, and platelets (small fragments in the blood) that transport oxygen, fight infection, and stop bleeding.

The effectiveness of Cosela was evaluated in three randomized, double-blind, placebo-controlled studies in patients with extensive-stage small cell lung cancer. Combined, these studies randomly assigned 245 patients to receive either an infusion of Cosela in their veins or a placebo before chemotherapy. The studies then compared the two groups for the proportion of patients with severe neutropenia (a very low count of white blood cells called neutrophils) and the duration of severe neutropenia in the first cycle of chemotherapy. In all three studies, patients who received Cosela had a lower chance of having severe neutropenia compared to patients who received a placebo. Among those who had severe neutropenia, patients who received Cosela, on average, had it for a shorter time than patients who received a placebo.

The most common side effects of Cosela include fatigue; low levels of calcium, potassium and phosphate; increased levels of an enzyme called aspartate aminotransferase; headache; and infection in the lungs (pneumonia).

Patients should also be advised about injection site reactions, acute drug hypersensitivity, interstitial lung disease/pneumonitis (lung tissue inflammation) and embryo-fetal toxicity.

Cosela received FDA Priority Review and Breakthrough Therapy designations for the indication noted above.

The FDA granted the approval of Cosela to G1 Therapeutics, Inc.

As readers of the AntonRx Report may know, we scan hundreds of articles each week to sleuth out information that is timely and important to specialty pharmacies. Earlier this week we ran across the first article we’ve seen that directly addresses Covid 19 and the specific impact to patients on a specialty therapy, in this case Rheumatoid Arthritis.

The article is a bit lengthy but offers a template for any specialty pharmacy to develop their own therapeutic protocol. Since virtually all specialty pharmacies are now accredited, it is incumbent on specialty pharmacies to develop such enhanced therapeutic protocols as new information becomes available.

The most noteworthy article element addressed medication dosing schedule adjustments for patients before / after receiving the Covid 19 vaccine.
“Medications include:
Methotrexate: Hold for one week after each vaccine dose for people with well-controlled disease.
JAK Inhibitors: Hold for one week after each dose.
Abatacept for subcutaneous delivery: Hold for one week before and one week after the first dose only; for IV delivery, time the first vaccine only to occur four weeks after the drug’s infusion, then postpone the subsequent infusion by one week, for a five-week gap.
Rituximab: Schedule vaccine about four weeks before next scheduled cycle and delay the drug two to four weeks after the vaccine series is completed, if possible.
Cyclophosphamide: Time drug administration about one week after each vaccine dose, if possible.
There were no recommendations to alter drug regimens for hydroxychloroquine, intravenous immunoglobulin (IVIG), prednisone less than 20 milligrams per day, sulfasalazine, leflunomide, mycophenolate, azathioprine, cyclophosphamide, TNF inhibitors, belimumab, oral calcineurin inhibitors, or IL-6R, IL-1, IL-17, IL-12/23, or IL-23.

It is possible that people taking immune-compromising medication may have a lower
response to the vaccine, the ACR Task Force notes.”

Does your specialty pharmacy support drug-specific dosing adjustments for your RA patients receiving the vaccine?
If not, why not?

Our suggestion is to use this template to prepare such enhanced protocols for each therapeutic category you support including desktop workflows for patient coordinators and pharmacists to determine if a dosing schedule adjustment is warranted. Notes to the patient file should include patient status and follow up to ensure that the specialty therapy resumes. A call to the treating physician may be required as well. Each manufacturer should be able to provide their dosing recommendation for their drug.

Developing a full suite of protocols will be challenging but is essential to a high-quality therapeutic management program.

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8 Things People With Rheumatoid Arthritis Must Know About the COVID-19 Vaccines

Learn about the safety, effectiveness, and importance of getting the COVID-19 vaccines if you or a loved one is living with rheumatoid arthritis.

By Meryl Davids Landau
Medically Reviewed by Alexa Meara, MD

February 11, 2021 — With two COVID-19 vaccines already authorized by the U.S. Food and Drug Administration (FDA) and others potentially on the way, immunizations have begun in the United States and around the world. People living with rheumatoid arthritis (RA) and their loved ones may have questions about whether the vaccines are safe and effective for those with this condition.

Based on a substantial body of evidence, there is no need to hesitate, says Onyema Ogbuagu, MBBCh, an infectious disease specialist and a principal investigator of the Pfizer COVID-19 vaccine trial at the Yale School of Medicine in New Haven, Connecticut.

People with rheumatoid arthritis should roll up their sleeves as soon as a shot is offered to them, he says. With COVID-19 a widely circulating, deadly disease, it’s important to get protection as soon as you can. “Don’t delay. Do it yesterday,” he urges.

Below are expert answers to your pressing questions about the COVID-19 vaccines……..
CLICK HERE TO READ THE FULL ARTICLE

Last week the FDA approved yet another uber expensive therapy, Evkeeza from Regeneron Pharmaceuticals, to treat homozygous familial hypercholesterolemia (HoFH), an ultra-rare inherited condition that affects approximately 1,300 patients in the U.S. and is characterized by extremely high low-density lipoprotein cholesterol (LDL-C)

Evkeeza is an infused therapy and is weight based. The recommended dosing regimen of Evkeeza is 15 mg per kilogram of body weight every 4 weeks. Evkeeza was also granted a pediatric indication and can be combined with other lipid lowering therapies. Evkeeza is the first FDA approved treatment that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein that plays a key role in lipid metabolism.

Wholesale Acquisition Cost (WAC) per patient in the U.S. will vary based on weight and is expected to be approximately $450,000 per year on average.

Orsini Specialty Pharmacy, a leader in rare diseases and gene therapies, has announced that it has been selected by Regeneron Pharmaceuticals as the exclusive specialty pharmacy partner for Evkeeza. Product will be shipped direct to the treating physician office, another example of a limited distribution – direct-to-office (LD-DTO) program. Orsini will also provide HUB services including product information, insurance benefit verification, community resources and appointment reminders.

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FDA Approves First-in-class Evkeeza for Patients with Ultra-rare Inherited Form of High Cholesterol

Feb. 11, 2021 /PRNewswire/ — Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately 1,300 patients in the U.S. and is characterized by extremely high low-density lipoprotein cholesterol (LDL-C)

In pivotal Phase 3 HoFH trial, adding Evkeeza to standard lipid-lowering therapies reduced LDL-C by nearly half at 24 weeks, compared to placebo

Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced that the U.S. Food and Drug Administration (FDA) approved EvkeezaTM (evinacumab-dgnb) as an adjunct to other low-density lipoprotein cholesterol (LDL-C) lowering therapies to treat adult and pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH). Evkeeza is the first FDA-approved treatment that binds to and blocks the function of angiopoietin-like 3 (ANGPTL3), a protein that plays a key role in lipid metabolism.

“The FDA’s approval of Evkeeza is a watershed moment…………
CLICK HERE TO READ THE FULL PRESS RELEASE

Earlier this month the FDA approved a new ORAL therapy, Tepmetko (tepotinib) from EMD Serono, for the treatment of naïve and previously treated patients with advanced or metastatic NSCLC with MET exon 14 skipping alterations.

Tepmetko is the only FDA approved MET inhibitor that offers once-daily oral dosing and is administered as two 225 mg tablets (450 mg).

Tepmetko is a precision medicine that advances patient access to a targeted treatment highlighted by routine comprehensive biomarker testing. It works as a tyrosine kinase inhibitor that targets the tyrosine kinase MET. MET is an enzyme, a type of protein, that is involved in various cellular processes. Its activity is abnormal or increased in cancer, which may lead to the uncontrollable growth of cells and tumor development.

Patients with this aggressive lung cancer are often elderly and face a poor clinical prognosis.

Tepmetko is the second drug with the same indication. In May of 2020, the FDA approved Tabrecta (capmatinib) from Novartis. Merck hasn’t confirmed the cost of therapy for Tepmetko, however, the list price for Tabrecta is $17,950 for a 28-day supply. Analysts believe that the two therapies will compete on price in this small patient population.

Merck did not indicate if Tepmetko will launch through limited distribution. By way of reference, the competing Novartis product (Tabrecta) launched through LD last year. We expect that Tepmetko will follow suit.

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FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer

On February 3, 2021, the Food and Drug Administration granted accelerated approval to tepotinib (Tepmetko, EMD Serono Inc.) for adult patients with metastatic non-small cell lung cancer (NSCLC) harboring mesenchymal-epithelial transition (MET) exon 14 skipping alterations.

Efficacy was demonstrated in the VISION trial (NCT02864992), a multicenter, non-randomized, open-label, multicohort study enrolling 152 patients with advanced or metastatic NSCLC with MET exon 14 skipping alterations. Patients received tepotinib 450 mg orally once daily until disease progression or unacceptable toxicity.

The main efficacy outcome measures were overall response rate (ORR) determined by a blinded independent review committee using RECIST 1.1 and response duration. Among the 69 treatment naïve patients, the ORR was 43% (95% CI: 32%, 56%) with a median response duration of 10.8 months (95% CI: 6.9, not estimable). Among the 83 previously treated patients, the ORR was 43% (95% CI: 33%, 55%) with a median response duration of 11.1 months (95% CI: 9.5, 18.5).

The most common adverse reactions (≥ 20% of patients) were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea. Tepotinib can also cause interstitial lung disease, hepatotoxicity, and embryo-fetal toxicity.

The recommended tepotinib dose is 450 mg orally once daily with food.

This indication is approved under accelerated approval based on overall response rate and response duration. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

This review used the Real-Time Oncology Review, which streamlined data submission prior to the filing of the entire clinical application. The review also used the Oncology Center of Excellence Assessment Aid and the Product Quality Assessment Aid (PQAA), voluntary submissions from the applicant to facilitate the FDA’s assessment.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this application, a modified Project Orbis was undertaken because of the timing of submission to other regulatory agencies. FDA collaborated with Health Canada, Therapeutic Goods Administration (Australia), and Swissmedic on this review.

This week the FDA approved a new ORAL therapy, Ukoniq (umbralisib) from TG Therapeutics with indications for marginal zone lymphoma (MZL) and follicular lymphoma (FL). (See FDA press release below for indication details.)

Accelerated Approval was granted well in advance of its scheduled approval date. Ukoniq, a dual inhibitor of PI3K-delta and CK1-epsilon, had submitted Phase 2 trial data as recently as this past December.

Follicular lymphoma (FL) is typically an indolent form of non-Hodgkin lymphoma (NHL) that arises from B-lymphocytes. It is the second most common form of NHL. FL is generally not curable and is considered a chronic disease, as patients can live for many years with this form of lymphoma. With an annual incidence in the United States of approximately 13,200 newly diagnosed patients, FL is the most common indolent lymphoma accounting for approximately 17 percent of all NHL cases.

Pricing for Ukoniq was not available.

The trend to launch new therapies, especially in Oncology, through Limited Distribution continues in 2021. TG Therapeutics has announced that Onco360 will be its exclusive specialty pharmacy for this therapy.

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FDA grants accelerated approval to umbralisib for marginal zone lymphoma and follicular

On February 5, 2021, the Food and Drug Administration granted accelerated approval to umbralisib (Ukoniq, TG Therapeutics), a kinase inhibitor including PI3K-delta and casein kinase CK1-epsilon, for the following indications:

Adult patients with relapsed or refractory marginal zone lymphoma (MZL) who have received at least one prior anti-CD20-based regimen;
Adult patients with relapsed or refractory follicular lymphoma (FL) who have received at least three prior lines of systemic therapy.

Approval was based on two single-arm cohorts of an open-label, multi-center, multi-cohort trial, UTX-TGR-205 (NCT02793583), in 69 patients with MZL who received at least one prior therapy, including an anti-CD20 containing regimen, and in 117 patients with FL after at least 2 prior systemic therapies. Patients received umbralisib 800 mg orally once daily until disease progression or unacceptable toxicity.

Efficacy was based on overall response rate (ORR) and duration of response (DOR) using modified 2007 International Working Group criteria assessed by an independent review committee.

For patients with MZL, the ORR was 49% (95% CI: 37.0, 61.6) with 16% achieving complete responses. Median DOR was not reached (95% CI: 9.3, NE) in these patients. For patients with FL, the ORR was 43% (95% CI: 33.6, 52.2) with 3% achieving complete responses. Median DOR was 11.1 months (8.3, 16.4).

The most common (>15%) adverse reactions, including laboratory abnormalities, were increased creatinine, diarrhea-colitis, fatigue, nausea, neutropenia, transaminase elevation, musculoskeletal pain, anemia, thrombocytopenia, upper respiratory tract infection, vomiting, abdominal pain, decreased appetite, and rash. Serious adverse reactions occurred in 18% of patients, most often from diarrhea-colitis and infection. Diarrhea-colitis and transaminase elevation were the most common reasons for dose modifications.

The prescribing information provides warnings and precautions for adverse reactions including infections, neutropenia, diarrhea and non-infectious colitis, hepatotoxicity, and severe cutaneous reactions.

The recommended umbralisib dose is 800 mg taken orally once daily with food until disease progression or unacceptable toxicity.

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

This application was granted priority review for the MZL indication and orphan drug designation was granted for the treatment of MZL and FL. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

The MZL and FL indications were granted accelerated approval based on overall response rate. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

Specialty pharmacies won’t be dispensing Breyanzi, approved by the FDA last week for the treatment of late-stage lymphoma with certain types of large B-cell lymphoma whose cancer has progressed after at least two prior treatments. This newly approved infused CAR-T therapy will be available only at select, vetted hospitals nationally.

The treatment is personalized, made up of a patient’s own immune cells extracted and shipped to special manufacturing facilities. There, the cells are genetically modified to target a particular protein that acts as a flag for the cancer. The modified cells are manipulated to create a 1 time treatment dose that is shipped back to the facility for infusion. One may even ask if it qualifies as a ‘medicine’.

Breyanzi will hit the market three years after the approvals in lymphoma of CAR-T cell therapies Yescarta (Gilead) and Kymriah (Novartis). Neither treatment is a big seller, with use mostly confined to blood cancer patients who have run out of traditional therapy options.

The FDA approved Breyanzi with a black box warning for the risk of neurotoxicity and a type of immune overreaction known as cytokine release syndrome associated with cell therapy. The FDA requires patients to be monitored in person or remotely for the first week after infusion and they must remain close to the facility for at least three more weeks. Bristol Myers will also provide wearable temperature monitors.

So why should specialty pharmacies want to know about a therapy that they can’t dispense?

More than 500 gene-based therapies are in development. So, specialty pharmacies should be concerned. We may start seeing even the most recent generation of ‘wonder drugs’ dispensed by SPs replaced by 1 dose gene therapies.

Also, SPs that work the Oncology segment should know about ALL specialty therapies in the toolbox. With more approvals of such space age therapies such expertise is important to build credibility with patients and Oncologists.

Bristol Myers will charge a list price of $410,300 for Breyanzi. Both Gilead and Novartis offer their competing therapies at ~$373,000. Bristol Myers did not mention offering any results-based financial guarantees.

Is this term in your pharmaceutical vocabulary?…… CAR-T.
CAR-T stands for chimeric antigen receptor T cell (CAR-T) therapy in which T-cells are extracted from a patient’s white blood cells and genetically modified in special facilities to target a specific protein that binds to cancer cells. The modified cells are then infused in the patient.

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FDA Approves New Treatment For Adults With Relapsed Or Refractory Large-B-Cell Lymphoma

February 05, 2021 — The U.S. Food and Drug Administration has approved Breyanzi (lisocabtagene maraleucel), a cell-based gene therapy to treat adult patients with certain types of large B-cell lymphoma who have not responded to, or who have relapsed after, at least two other types of systemic treatment. Breyanzi, a chimeric antigen receptor (CAR) T cell therapy, is the third gene therapy approved by the FDA for certain types of non-Hodgkin lymphoma, including diffuse large B-cell lymphoma (DLBCL). Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

“Today’s approval represents another milestone in the rapidly progressing field of gene therapy by providing an additional treatment option for adults with certain types of cancer affecting the blood, bone marrow, and lymph nodes,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “Gene and cell therapies have evolved from promising concepts to practical cancer treatment regimens.”

DLBCL is the most common type of non-Hodgkin lymphoma in adults. Non-Hodgkin lymphomas are cancers that begin in certain cells of the immune system and can be either fast-growing (aggressive) or slow-growing. Approximately 77,000 new cases of non-Hodgkin lymphoma are diagnosed in the U.S. each year and DLBCL represents approximately one in three newly diagnosed cases.

Each dose of Breyanzi is a customized treatment created using a patient’s own T-cells, a type of white blood cell, to help fight the lymphoma. The patient’s T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing of the lymphoma cells. Once the cells are modified, they are infused back into the patient.

The safety and efficacy of Breyanzi were established in a multicenter clinical trial of more than 250 adults with refractory or relapsed large B-cell lymphoma. The complete remission rate after treatment with Breyanzi was 54%.

Treatment with Breyanzi has the potential to cause severe side effects. The labeling carries a boxed warning for cytokine release syndrome (CRS), which is a systemic response to the activation and proliferation of CAR T cells, causing high fever and flu-like symptoms and neurologic toxicities. Both CRS and neurological events can be life-threatening. Other side effects include hypersensitivity reactions, serious infections, low blood cell counts and a weakened immune system. Side effects generally appear within the first one to two weeks following treatment, but some side effects may occur later.

Because of the risk of CRS and neurologic toxicities, Breyanzi is being approved with a risk evaluation and mitigation strategy (REMS) which includes elements to assure safe use (ETASU). The FDA is requiring, among other things, that healthcare facilities that dispense Breyanzi be specially certified. As part of that certification, staff involved in the prescribing, dispensing or administering of Breyanzi are required to be trained to recognize and manage the risks of CRS and neurologic toxicities. The REMS program specifies that patients be informed of the signs and symptoms of CRS and neurological toxicities following infusion – and of the importance of promptly returning to the treatment site if they develop fever or other adverse reactions after receiving treatment with Breyanzi.

To further evaluate the long-term safety, the FDA is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Breyanzi.

The FDA granted Breyanzi Orphan Drug, Regenerative Medicine Advanced Therapy (RMAT) and Breakthrough Therapy designations. The RMAT designation program was created under the 21st Century Cures Act to help facilitate the expeditious development of regenerative medicine therapies intended for serious conditions. Breyanzi is the first regenerative medicine therapy with RMAT designation to be licensed by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. The Breyanzi application was reviewed using a coordinated, cross-agency approach, including both the Center for Biologics Evaluation and Research and FDA’s Oncology Center of Excellence.

The FDA granted approval of Breyanzi to Juno Therapeutics Inc., a Bristol-Myers Squibb Company.