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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.

During 2020 we saw a measurable uptick in the number of FDA approved therapies that were LD-DTO….. which you should know stands for Limited Distribution, Direct-to-Office (LD-DTO) for office administration. 

Manufacturers have gotten very comfortable with specialty pharmacies dispensing their products and managing patients through traditional Limited Distribution (LD) direct to patient. They are rapidly warming up to the idea of specialty pharmacies also handling their buy-and-bill meds, especially for orphan drugs and those that may be out of the ordinary and in need of some ‘specialty’ tender lovin’ care. 

Here’s an example of a new application of LD-DTO that we tripped across recently. 

Orsini Specialty Pharmacy was selected some months ago by Glaukos Manufacturing to manage a drug originally launched in 2016. The therapy, Photrexa / Photrexa Viscous, is shipped DTO and is used incident to a procedure called corneal collagen cross-linking (CXL) by a corneal specialist. 

So why go to Orsini to set up a specialty pharmacy LD-DTO solution years after original launch? The specialists were still running into reimbursement issues, challenges with inventorying high cost therapy, and complicated billing practices as the drug incident to an eye laser procedure. 

The drug has an AWP of $3750 per eye….. so it is in the specialty pharmacy sweet spot. Orsini has worked with payers and PBMs to open up the AOB billing option and those efforts are paying off. Specialists and patients are equally enjoying the journey on increasingly smoother roads. 

As other manufacturers see the benefits of such a relationship we will likely see more LD-DTO deals in the future.    

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Orsini Specialty Pharmacy Selected By Glaukos® Corporation As A Specialty Pharmacy Distribution Partner For Photrexa® And Photrexa® Viscous 

ELK GROVE VILLAGE, Ill., Jan. 19, 2021 /PRNewswire/ — Orsini Specialty Pharmacy, a leader in rare diseases and gene therapies, announced today that it has been selected by Glaukos® Corporation as a specialty pharmacy distribution partner for Photrexa® (riboflavin 5′-phosphate ophthalmic solution) and Photrexa® Viscous (riboflavin 5′-phosphate in 20% dextran ophthalmic solution) for the treatment of patients with progressive keratoconus and corneal ectasia following refractive surgery. Using Photrexa Viscous and Photrexa with a proprietary UV light delivery system, Glaukos’ iLink™ corneal cross-linking procedure is the first and only FDA approved therapeutic treatment that strengthens the cornea to slow or halt the progression of keratoconus. 

Keratoconus is a rare, degenerative eye condition that occurs when the normally dome-shaped cornea weakens and begins to bulge into a cone-like shape resulting in vision loss. Keratoconus often appears in individuals who are in their late teens to early 20s and occurs in approximately 1 out of every 2,000 people in the United States.   

“We are honored to be Glaukos’ specialty pharmacy partner for Photrexa, which offers hope for individuals with progressive keratoconus,” said Mike Fieri, Orsini Chief Executive Officer. “Our dedicated Photrexa Care Team is committed to providing high touch, individualized services for people with this condition.” 

Tim Homer, Vice-President of Global Market Access added, “We at Glaukos are excited to partner with Orsini. This partnership offers our providers the option of obtaining Photrexa through a specialty pharmacy so they can focus on providing access to the iLink procedure to their patients.” 

About Orsini Specialty PharmacyProviding patients with comprehensive and compassionate care since 1987, Orsini is a leading, independent specialty pharmacy focused on rare and ultra-rare diseases and gene therapies. Orsini’s high touch care model is centered around experienced, therapy-specific care teams who provide personalized care to patients based on their specific condition and treatment. The company’s comprehensive solutions include medication adherence programs, data analytics, customized manufacturer programs and nationwide nursing coverage for convenient in-home infusion services. Headquartered in Elk Grove Village, IL, Orsini Specialty Pharmacy holds accreditations with the Accreditation Commission for Health Care (ACHC), The Joint Commission, URAC, NABP, and most recently was awarded ACHC’s Distinction in Rare Diseases and Orphan Drugs. 

About Glaukos CorporationGlaukos (www.glaukos.com) is an ophthalmic medical technology and pharmaceutical company focused on novel therapies for the treatment of glaucoma, corneal disorders and retinal diseases. The company pioneered Micro-Invasive Glaucoma Surgery, or MIGS, to revolutionize the traditional glaucoma treatment and management paradigm. Glaukos launched the iStent®, its first MIGS device, in the United States in July 2012, its next-generation iStent inject® device in the United States in September 2018 and most recently, its iStent injectW device in the United States in October 2020. In corneal health, Glaukos’ proprietary suite of single-use, bio-activated pharmaceuticals are designed to strengthen, stabilize and reshape the cornea through a process called corneal collagen cross-linking to treat corneal ectatic disorders and correct refractive conditions. Glaukos is leveraging its platform technology to build a comprehensive and proprietary portfolio of micro-scale surgical and pharmaceutical therapies in glaucoma, corneal health and retinal disease. 

For more information about Orsini’s specialty pharmacy services, contact us at 847-734-7373 ext. 545, e-mail us at orsini@orsinihc.com, or visit https://www.orsinispecialtypharmacy.com/. 

iLink™ is a trademark of Glaukos Corporation. Glaukos and Photrexa® are registered trademarks of Glaukos Corporation.

The FDA has approved a new, first ever therapy for Lupus nephritis, Lupkynis (voclosporin) from Aurinia Pharmaceuticals, in combination with background immunosuppressive therapy. It is indicated for the treatment of adult patients with active lupus nephritis (LN) . Lupus nephritis (LN) is a serious progression of SLE, a chronic, complex, and autoimmune disease.

Lupkynis has been approved with a black box warning including malignancies and serious infections.

About 200,000-300,000 people live with SLE in the U.S. and approximately one out of three of these individuals, +-85,000, have already developed LN at the time of SLE diagnosis. If poorly controlled, LN can lead to permanent and irreversible tissue damage within the kidney, resulting in kidney failure.

In the past, repurposed anti-inflammation drugs, steroids, immunosuppressants and antimalarials like hydroxychloroquine were the only options to manage lupus symptoms. The last approval for LN was ten years ago in 2011, Benlysta.

Aurinia announced in an investor call that it has targeted ~12,000 physicians in the rollout and has already approached ~50 payers that cover two-thirds of LN lives in the US.

Forecasting patient cost is not easy.
Aurinia announced a list price of $3,950 for 60 capsules. But that translates into only 10 days of therapy at the start up (also ongoing) dosing schedule. However, the label details complex dose reductions based on close physician monitoring and lab results especially in the first months. So, a patient that well tolerates the drug will require a maximum of 180 capsules a month….. that’s ~$12,000. A patient with complications may see dose reduction by up to two thirds, requiring only 2 tablets a day / 60 tablets a month….. that’s ~$4,000. Analysts suggest that once up and running the weighted average annual cost of therapy will likely top out at about $65,000.

Aurinia did not release distribution details. We expect that Lupkynis will launch into specialty pharmacy limited distribution given the cost of therapy, a black box warning, a complex dosing regimen, and testing for adverse reactions long term.

FDA Approves Aurinia Pharmaceuticals’ LUPKYNIS™ (voclosporin) for Adult Patients with Active Lupus Nephritis

• LUPKYNIS is the first FDA-approved oral therapy for lupus nephritis (LN), a condition that causes irreversible kidney damage and increases the risk of kidney failure, cardiac events, and death –
• LUPKYNIS demonstrated significantly improved renal response rates compared to typical standard-of-care (SoC) in clinical trials
• LUPKYNIS is now commercially available in the U.S. – JANUARY 22, 2021 VICTORIA, British Columbia & ROCKVILLE, Md.–(BUSINESS WIRE)– Aurinia Pharmaceuticals Inc. today announced that the U.S. Food and Drug Administration (FDA) has approved LUPKYNIS (voclosporin) in combination with a background immunosuppressive therapy regimen to treat adult patients with active lupus nephritis (LN). LUPKYNIS is the first FDA-approved oral therapy for LN. LN causes irreversible kidney damage and significantly increases the risk of kidney failure, cardiac events, and death. It is one of the most serious and common complications of the autoimmune disease systemic lupus erythematosus (SLE). LUPKYNIS is now available to patients in the United States (U.S.).

In pivotal trials,………………………
CLICK HERE TO ACCESS THE FULL PRESS RELEASE

The 340b program is once again in the news. All the wailing and gnashing of teeth over recent years boiled over on 2020 with a bright red line in the sand drawn by manufacturers against covered entities. The battle cry “We’re not gonna take it anymore!” resulted in manufacturers not providing drug at 340b acquisition prices to the many contract pharmacies nationally that dispense those drugs to eligible patients. That created a big problem for the covered entities and put a kink in the revenue pipeline for the many retail contract pharmacies and specialty pharmacies.

As you may recall from prior coverage of the 340b skirmishes, the 340b program was implemented to ensure that disproportionate share hospitals (by definition, those that serve mostly economically underprivileged patients) can obtain drugs at the deepest discount offered and, theoretically, pass those saving on to patients. Sounds great, huh? But Pharma doesn’t think that is what is happening. As detailed in a recent article below, Pharma continues to hold the line against the hospitals saying that they are gaming the program with rampant double dipping of discounts (340b and Medicaid). And, they also accuse covered entities of not passing the savings on to patients.

To the Battlements
Hospitals have benefited greatly by the savings and they don’t want to see them go away. In response, the hospitals ramped up a massive PR campaign in 2020 with special focus on Congress. They showed that it is easier to get a politician to respond favorably to a plea to help patients get access to desperately needed drugs vs. manufacturer claims that they are being robbed. They were particularly keen on strong arming HHS, which controls the 340b program, that the manufacturers’ policies violate the 340B statute.

In short, the end of 2020 was not the best time to get Congress or HHS to get involved. Hence, Plan B was implemented by the covered entities. Lawsuits are now seeking court relief to return the status quo. They are even seeking damages!

Pharmacies Continue to be Caught in the Middle
The big box SPs dispense the bulk of specialty meds in the program, but, many independent specialty pharmacies are also very active as hospitals can contract with multiple pharmacies. The pharmacies then earn a dispensing fee which, more often than not, generates more net revenue than the usual margin earned on a routine ‘fill’ for the same, non-discounted drug.

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340B Rollback Prompts Action by Stakeholders

JANUARY 20, 2021 — The dispute between drugmakers and covered entities under the 340B Drug Pricing Program has ramped up, as a number of hospital and pharmacy associations are suing the Department of Health and Human Services to undo manufacturer limitations on 340B discounts.

Their efforts have paid off: On Dec. 30, HHS issued an advisory opinion stating that drug manufacturers are required to deliver 340B discounts on covered outpatient drugs when contract pharmacies are acting as agents of 340B covered entities. Although advisory opinions do not carry the force of law, “they set out the agency’s current views on issues,” HHS said in a statement. “Those views may be reflected in the … enforcement and oversight powers the federal government has to run the 340B Program.”

Beginning in mid-2020, a growing number of drug companies have restricted discounted sales of almost all drugs to covered entities dispensing 340B drugs through contract pharmacies, which a majority of 340B covered entities use as a channel for providing the discounted drugs. As per the 340B statute, manufacturers and covered entities cannot file lawsuits against one another, which is why HHS is the defendant for all of the covered entity lawsuits targeting manufacturer actions.

“Ideally, this should have been……….

CLICK HERE TO ACCESS THE FULL ARTICLE

Last week the FDA approved a new specialty therapy for adult HIV positive patients.

Be patient, it will take some time to explain this announcement as there are several moving parts.

The new therapy is Cabenuva from ViiV.
Now pay attention…..
The biggest difference with 95% of the other HIV oral therapy options is that Cabenuva is administered monthly by intramuscular injection in the gluteus. Cabenuva is a combo therapy that includes one injection for cabotegravir and a second injection for rilpivirine, each is an extended-release injectable suspension. It is meant to be administered in the physician’s office.

But….. The FDA also approved a new ORAL form of cabotegravir called Vocabria along with ORAL rilpivirine (already approved under the brand name Edurant). Why? This one month course is taken prior to the initiation of the injectable combo therapy to ensure the medications are well-tolerated.

The new combo was made available in Europe last year and patient feedback has been surprisingly popular in spite of the fact that the therapy requires an office visit for the monthly injections. A patient survey in Europe showed that two-thirds of HIV patients were “likely” to switch to a long-acting injectable regimen. ViiV also said that feedback in the US is even higher.

Are there benefits to the injectable regimen?
Reduced pill burden. As with injectable therapies in other therapeutic categories, a once a month office injection can correct poor compliance with a daily oral therapy (often requiring multiple drugs daily). Poor compliance on HIV orals has been associated with developing drug resistance.
HIV patients are concerned with their privacy. A once a month office injection eliminates having lots of HIV pills in the medicine cabinet.
HIV patients typically see a clinician only about every 3-6 months. Seeing a clinician monthly facilitates virus level monitoring, promotes disease education, nutrition and psychological counseling, and identification of emergent concomitant medical issues.
While the FDA approval now only covers monthly use, word is that ViiV will seek approval for bimonthly administration. A big problem with HIV therapy has been missed doses, very often due to loss of insurance coverage. A two month, long-acting injectable regimen would help bridge coverage gaps.

So, will patients flock to Cabenuva ?
Uptake of this new option may most influenced by cost. Therapy will run about $4,000 per month after the induction first dose at $6,000.

How will Payers handle benefit / coverage policies — and Access for Cabenuva?
The ORAL portion of the regimen can be placed under the pharmacy benefit and would likely be available through open access like almost all HIV meds. Since the injectable schedule is office administered one would assume that Cabenuva would be obtained through wholesalers via buy-and-bill. However, given its cost and unknown demand, offices /clinics may be hesitant to stock up on the product. Precedent also shows that such injectables are increasingly placed with specialty pharmacies for limited distribution – direct-to-office (our research shows that the few previously approved HIV injectables all launched LD-DTO). We await to hear details from ViiV.

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FDA approved CABENUVA (cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension), co-packaged for intramuscular use.

First FDA-approved injectable, complete regimen for HIV-1 infected adults that is administered once a month.

FDA also approved VOCABRIA (cabotegravir) 30 mg tablets which should be taken in combination with oral rilpivirine (EDURANT) for one month prior to starting treatment with Cabenuva to ensure the medications are well-tolerated before switching to the extended-release injectable formulation. The EDURANT (rilpivirine) tablet label was revised to reflect the oral lead-in recommendations for use with VOCABRIA.

VOCABRIA is a human immunodeficiency virus type-1 (HIV-1) integrase strand transfer inhibitor (INSTI) indicated in combination with EDURANT (rilpivirine) for short-term treatment of HIV-1 infection in adults who are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine, for use as:
• oral lead-in to assess the tolerability of cabotegravir prior to administration of CABENUVA (cabotegravir; rilpivirine) extended-release injectable suspensions.
• oral therapy for patients who will miss planned injection dosing with CABENUVA.

CABENUVA, a 2-drug co-packaged product of cabotegravir, a human immunodeficiency virus type-1 (HIV-1) integrase strand transfer inhibitor (INSTI), and rilpivirine, an HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI), is indicated as a complete regimen for the treatment of HIV-1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no history of treatment failure and with no known or suspected resistance to either cabotegravir or rilpivirine.

Dosing and Administration:
The recommended dosing is as follows:
The recommended oral lead-in daily dose is one 30-mg tablet of VOCABRIA (cabotegravir) and one 25-mg tablet of EDURANT (rilpivirine).
Intramuscular Injection Dosing with CABENUVA
Initiation Injections (CABENUVA 600-mg/900-mg Kit)
Initiate injections on the last day of oral lead-in. CABENUVA contains cabotegravir and rilpivirine extended-release injectable suspensions. The recommended initial injection doses of CABENUVA in adults are a single 600-mg (3-mL) gluteal intramuscular injection of cabotegravir and a single 900-mg (3-mL) gluteal intramuscular injection of rilpivirine. Administer cabotegravir and rilpivirine at separate gluteal injection sites (on opposite sides or 2 cm apart) during the same visit. Continuation injections should be initiated a month after the initiation injections.

Continuation Injections (CABENUVA 400-mg/600-mg Kit)
After the initiation injections, the recommended monthly continuation injection doses of CABENUVA in adults are a single 400-mg (2-mL) gluteal intramuscular injection of cabotegravir and a single 600 mg (2-mL) gluteal intramuscular injection of rilpivirine at each visit. Administer cabotegravir and rilpivirine at separate gluteal injection sites (on opposite sides or 2 cm apart) during the same visit. Patients may be given CABENUVA up to 7 days before or after the date the patient is scheduled to receive monthly injections.

Missed Injections
Adherence to the monthly injection dosing schedule is strongly recommended. Patients who miss a scheduled injection visit should be clinically reassessed to ensure resumption of therapy remains appropriate.

Planned Missed Injections (Oral Dosing to Replace Up to 2 Consecutive Monthly Injections)
If a patient plans to miss a scheduled injection visit by more than 7 days, take daily oral therapy to replace up to 2 consecutive monthly injection visits. The recommended oral daily dose is one 30-mg tablet of VOCABRIA (cabotegravir) and one 25-mg tablet of EDURANT (rilpivirine). The first dose of oral therapy should be taken approximately 1 month after the last injection dose of CABENUVA and continued until the day injection dosing is restarted.
Unplanned Missed Injections
If monthly injections are missed or delayed by more than 7 days and oral therapy has not been taken in the interim, clinically reassess the patient to determine if resumption of injection dosing remains appropriate

Injection Dosing Recommendations after Missed Injections
Less than or equal to 2 months since last injection:
Resume with 400-mg (2-mL) cabotegravir and 600-mg (2-mL) rilpivirine intramuscular monthly injections as soon as possible.
Greater than 2 months since last injection:
Re-initiate the patient with 600-mg (3-mL) cabotegravir and 900-mg (3 mL) rilpivirine intramuscular injections then continue to follow the 400 mg (2 mL) cabotegravir and 600-mg (2-mL) rilpivirine intramuscular monthly injection dosing schedule

Summary of Clinical Studies:
The efficacy of CABENUVA has been evaluated in two Phase 3 randomized, multicenter, active-controlled, parallel-arm, open-label, non-inferiority trials:
• Trial 201584 (FLAIR, [NCT02938520]), (n = 629): HIV-1–infected, antiretroviral treatment (ART)-naive subjects received a dolutegravir INSTI-containing regimen for 20 weeks (either dolutegravir/abacavir/lamivudine or dolutegravir plus 2 other NRTIs if subjects were HLA-B*5701 positive). Subjects who were virologically suppressed (HIV-1 RNA less than 50 copies/mL, n = 566) were then randomized (1:1) to receive either a cabotegravir plus rilpivirine regimen or remain on the current antiretroviral regimen. Subjects randomized to receive cabotegravir plus rilpivirine initiated treatment with daily oral lead-in dosing with one 30-mg VOCABRIA (cabotegravir) tablet plus one 25-mg EDURANT (rilpivirine) tablet for at least 4 weeks followed by monthly injections with CABENUVA for an additional 44 weeks.
• Trial 201585 (ATLAS, [NCT02951052]), (n = 616): HIV-1–infected, ART-experienced, virologically-suppressed (for at least 6 months; median prior treatment duration was 4.3 years) subjects (HIV-1 RNA less than 50 copies/mL) were randomized and received either a cabotegravir plus rilpivirine regimen or remained on their current antiretroviral regimen. Subjects randomized to receive cabotegravir plus rilpivirine initiated treatment with daily oral lead-in dosing with one 30-mg VOCABRIA (cabotegravir) tablet plus one 25-mg EDURANT (rilpivirine) tablet for at least 4 weeks followed by monthly injections with CABENUVA for an additional 44 weeks.

The primary analysis was conducted after all subjects completed their Week 48 visit or discontinued the trial prematurely.

The primary endpoint of FLAIR and ATLAS was the proportion of subjects with plasma HIV-1 RNA greater than or equal to 50 copies/mL at Week 48.

Adverse Reactions:
The safety assessment of CABENUVA is based on the analysis of pooled 48-week data from 1,182 virologically suppressed subjects with HIV-1 infection in 2 international, multicenter, open-label pivotal trials, FLAIR and ATLAS.
The most common adverse reactions (Grades 1 to 4) observed in ≥2% of subjects receiving CABENUVA were injection site reactions, pyrexia, fatigue, headache, musculoskeletal pain, nausea, sleep disorders, dizziness, and rash.

Injection-Associated Adverse Reactions
Local Injection Site Reactions (ISRs): The most frequent adverse reactions associated with the intramuscular administration of CABENUVA were ISRs. After 14,682 injections, 3,663 ISRs were reported. One percent (1%) of subjects discontinued treatment with CABENUVA because of ISRs. Most ISRs were mild (Grade 1, 75%) or moderate (Grade 2, 36%). Four percent (4%) of subjects experienced severe (Grade 3) ISRs, and no subjects experienced Grade 4 ISRs.

An acquisition that has material implications for the specialty pharmacy industry was announced last week. Shields Health Solutions acquired ExceleraRx for an undisclosed amount. Like ExceleraRx, Shields has been busy building a large network of healthcare system owned specialty pharmacies. ExceleraRx, as our readers should know, has been aggressively pursuing the same segment, healthcare system owned specialty pharmacies. (We’ve been covering ExceleraRx since 2013.)

In a December press release ExceleraRx claimed 25 SP network deals. The press release below states that Shields has outpaced them with 65 health care systems with 700 hospitals in 43 states.

The merged company is expected to reach a $2 billion revenue rate (yes, specialty revenue) next year, more than enough volume to finally impress payors and manufacturers. (Read an unrelated article, Health Systems Versus Payors: A Duel for SP Care, on the challenges such networks have faced gaining payor access. CLICK HERE)

There is some extra icing on the ExceleraRx cake…. they bring a robust manufacturer marketing program, a home infusion solution to create health system owned infusion operations, and even a PBM to the party.

Side note—- In July 2019, Shields Health sold a combined ownership stake of about 50 percent to Walgreens and investment firm Welsh, Carson, Anderson & Stowe in a deal valued at between $850 million and $900 million. It will be interesting to see how the synergies play out and if the relationship can be leveraged.

Final note—- We remain convinced that healthcare system owned specialty pharmacies pose one of the greatest threats to independent specialty pharmacies given their ability to self-direct specialty prescriptions within their walls.

The FDA actually did a remarkable job in 2020 approving new drugs. In spite of the pandemic they managed to approve 53 novel drugs. That’s five more than 2019, when the FDA issued 48 approvals and only a bit short of the all-time record of 59 approvals in 2018. 
But if you use the 2020 number of 53 you would be wrong! Huh??Yep, the real count is 56! 

That’s because all the pundits that issue prior year recaps forget something…. there are also approvals for BIOLOGICS. The specialty pharmacy industry was founded on biologics, but that has shifted substantially in recent years. In 2020 there were only two BLA approvals, one for Tecartus (a gene therapy for cancer), and another for SevenFact (hemophilia).
So, are you saying, “OK wise guy, you are only up to 55, not 56!” My response would be…. ‘Hold yer horses, pardner.’If you look very closely, you’ll see that the FDA granted a new NDC for an old drug, Jelmyto, a cancer therapy reintroduced in a new formulation. We include this one in our annual count as it appears it will be launched via specialty pharmacy limited distribution.

But, what’s the big news in this otherwise totally exciting recap?We’ve created a spreadsheet for your perusal….. and one thing jumps off the page….. of the 33 specialty pharmacy NDA approvals in 2020 only 2 are available through Open Access. The rest will launch through Limited Distribution! The spreadsheet details each new specialty drug and our determination of its LD status. (See the NOTE below for an important disclaimer.)
CLICK HERE TO DOWNLOAD THE SPREADSHEET FROM THE ANTON HEALTH WEBSITE

The Impact of the LD Model

In past years specialty pharmacies were able to benefit from three things to grow their businesses. First, price increases. Second, utilization increases for existing therapies. And last, and perhaps most important, NEW PRODUCTS that usually generate larger per script revenues that boost profit margins. Additionally, new products often allow specialty pharmacies to expand into new therapeutic categories. In 2020 only a handful of the leading specialty pharmacies were the beneficiaries of launching 96% of 2020 specialty approvals via Limited Distribution (some exclusively) including therapies that we’ve classified as Limited Distribution DTO (direct-to-office as a distributor, not as a pharmacy, and most often under the medical benefit).

NOTE: We try to confirm each suspected Limited Distribution (LD) designation. In some cases, manufacturers may name the specialty pharmacy or pharmacies they have selected or simply say that the product will not be available through open access, or nothing at all. When unsure, we seek out key industry contacts to confirm if LD is in play.

Last word—– The article below is worth a quick read to learn about the most noteworthy 2020 approvals, both specialty and non-specialty.

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BIGGEST NOVEL DRUG APPROVALS IN 2020
Jan. 4, 2021 — 2020 was a peculiar year for drug approvals, partly because the ongoing COVID-19 pandemic delayed many clinical trials. Another reason is because several of the highly anticipated drug approvals for the year were surprising failures, such as Novartis’ inclisiran for hyperlipidemia in adults, FibroGen’s roxadustat for anemia in chronic kidney disease, and Gilead Sciences’ filgotinib in rheumatoid arthritis. Some of them may make a comeback in 2021 or later, but they did not hit the mark for one reason or another in 2020.
On the other hand, the pandemic and the astonishing innovations of numerous pharmaceutical companies created drugs to treat COVID-19 in record time. Here’s a look at the top 10 novel drug approvals of 2020, ……………………
CLICK HERE TO ACCESS THE FULL ARTICLE

WOW….. Centene is ponying up $2.2 billion to acquire Magellan Health!

This comes on the heels of Centene’s recently announced acquisition of PANTHER Rx only a couple of weeks ago. In the Anton Rx Report we sent on December 22nd we learned about Centene’s acquisition spree over recent years which explains a lot of their strategy.

With growing concerns about the future, PBMs are turning towards consolidation and acquisition. You need not go further than the CIGNA /Express Scripts acquisition to realize that big changes have already transpired in the industry. It was no surprise that in April 2019 Magellan was rumored to be courted by both United Healthcare (Optum) as well as Aetna (itself acquired by CVS).

Centene was ranked #42 in the Forbes 500 in May of 2020 while Magellan slipped in at #432. So, let’s look at why Magellan is a good fit for Centene and where Magellan’s specialty pharmacy business can further bolster this critical business segment.

Magellan is an interesting company.
It acquired ICORE in June of 2006 for more than $200 million as its first foray into the world of pharmacy. That was a smart move as the former ICORE unit has since contributed significantly to Magellan’s bottom line with a solid book of specialty pharmacy business. In June of 2009 Magellan acquired Coventry’s First Health Services, a small PBM.

Magellan must have liked what it saw because in the fall of 2011 Magellan announced a rebranding of the ICORE unit into Magellan Pharmacy Solutions (now Magellan Rx), and also announced that they were coming to market with a full service PBM product to run with the big dogs in the PBM pack. To bolster their position Magellan then acquired Partners Rx for $100 million adding 300,000 covered lives in the fall of 2013. Then in May 2014, Magellan acquired CDMI for over $300 million. After that, Magellan followed with the purchase of two other small PBMs…4D in 2015 ($55 million), and Veridicus in 2016 ($74.5 million). Since then, the pharmacy unit has grown but, no surprise, has faced very stiff competition.

As we know, PBM survival requires lives on the table —- ever bigger numbers — to negotiate with pharmacy chains and manufacturers. So, acquisitions (especially accretive) make great sense. PBMs need to shore up margin per member….. especially if other revenue streams – like rebates – fade away.

Magellan also cut its teeth on specialty pharmacy management under not just the pharmacy benefit but also under the medical benefit. This experience makes Magellan all the more attractive to Centene. But as with rebates, the competition within medical pharmacy management is increasing significantly.

Magellan is also diversified. It has a long history of behavioral health and radiology management services which would be icing on the Centene already tasty healthcare cake.

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Centene Signs Definitive Agreement to Acquire Magellan Health

Acquisition will broaden and deepen Centene’s whole health capabilities, while establishing a leading behavioral health platform at a critical time
Combined platform to deliver better health outcomes for complex populations through the integration of physical and mental health care
Important addition to Centene’s Health Care Enterprises, under which Magellan Health will continue to operate independently
Focus on creating next generation behavioral health platform, aligned with Centene’s technology strategy with additional growth opportunities in specialty care and pharmacy
Magellan Health CEO and management to remain in leadership roles, bringing additional talent to Centene and providing continuity
Value creation for shareholders through cost synergies and new growth opportunities

ST. LOUIS and PHOENIX, Jan. 4, 2021 /PRNewswire/ — Centene Corporation (NYSE: CNC) and Magellan Health, Inc. (NASDAQ: MGLN) today announced that they have entered into a definitive merger agreement under which Centene will acquire Magellan Health for $95 per share in cash for a total enterprise value of $2.2 billion. The transaction, which was unanimously approved by the Boards of Directors of both companies, will broaden and deepen Centene’s whole health capabilities and establish a leading behavioral health platform. The combined platform lays the foundation by which the company will continue to invest and innovate for its members, enabling improved health outcomes and faster, diversified growth.

The combination brings together the companies’ complementary capabilities in behavioral health, specialty healthcare and pharmacy management. As a result of the transaction, Centene will establish one of the nation’s largest behavioral health platforms across 41 million unique members with enhanced capabilities to deliver better health outcomes for complex, high-cost populations. Magellan Health will also add to Centene’s leadership in government sponsored healthcare, bringing 5.5 million new members on government-sponsored plans. Magellan Health also provides specialty health services for 18 million third-party customer members in addition to Centene’s own members. Furthermore, the transaction adds 2 million PBM members and 16 million medical pharmacy members, enhancing the scale of Centene’s pharmacy platform with leading capabilities in specialty drug management. As part of Centene’s Health Care Enterprises, Magellan Health will continue to independently support its existing customers and pursue growth opportunities. In addition, the transaction will create attractive shareholder returns through enhanced service capabilities, cross-sell opportunities……………………………

CLICK HERE TO ACCESS THE FULL ARTICLE

We recently sent an RxReport detailing the FDA approval of Orgovyx as the last FDA approval in 2021. That was technically correct….. but there is one last approval that we’ll cover today that officially closes out 2020. Look for a detailed 2020 look-back next week.

Earlier in December the FDA approved another biosimilar, Riabni from Amgen, for Non-Hodgkin’s Lymphoma (NHL) and several related conditions. Riabni is an infused therapy and is Amgen’s fifth US biosimilar approval.

Riabni will join two other Rituxan biosimilars, Genentech’s Truxima (11/19) and Pfizers’s Ruxience (07/19). Riabni will launch in the U.S. this month.

Riabni is being priced at a WAC of $716.80 per 100 mg or $3,584.00 per 500 mg single-dose vial, 23.7% less than the WAC for Rituxan, 15.2% less than the WAC for Truxima and matching the WAC for Ruxience. This price is equivalent to a discount of 16.7% below Rituxan’s Average Selling Price (ASP). So much for those 30%+discounts promised years ago.

Specialty pharmacies again won’t be jumping for joy with this approval. First, Riabni is an infused therapy and, secondly, it will be readily available from both wholesalers and specialty distributors.

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FDA Approves Amgen’s Riabni (rituximab-arrx), a Biosimilar To Rituxan (rituximab)

THOUSAND OAKS, Calif., Dec. 17, 2020 /PRNewswire/ — Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved Riabni (rituximab-arrx), a biosimilar to Rituxan® (rituximab), for the treatment of adult patients with Non-Hodgkin’s Lymphoma (NHL), Chronic Lymphocytic Leukemia (CLL), Granulomatosis with Polyangiitis (GPA) (Wegener’s Granulomatosis), and Microscopic Polyangiitis (MPA).

“The approval of Riabni represents an important milestone across our biosimilar and oncology portfolios,” said Murdo Gordon, executive vice president of Global Commercial Operations at Amgen. “Following the proven success of Kanjinti (trastuzumab-anns) and Mvasi (bevacizumab-awwb) in the U.S. marketplace, Riabni reaffirms Amgen’s long-term commitment to providing high quality biosimilars that can potentially offer more affordable, effective treatment options for cancer and other serious diseases and that contribute to the sustainability of healthcare systems.”

Riabni, a CD20-directed cytolytic antibody, was proven to be highly similar to Rituxan based on a totality of evidence, which included comparative analytical, nonclinical and clinical data, with no clinically meaningful differences in safety or effectiveness. The data package was composed of, in part, results from a pharmacokinetic (PK) similarity study and a comparative clinical study.

The randomized, double-blind, comparative clinical study evaluated the efficacy, pharmacokinetics (PK), pharmacodynamics (PD), safety, tolerability and immunogenicity of Riabni compared to Rituxan in subjects with grade 1, 2, or 3a follicular B-cell NHL and low tumor burden. There were 256 patients enrolled and randomized (1:1) to receive 375 mg/m2 intravenous infusion of either Riabni or Rituxan, once weekly for 4 weeks followed by dosing at weeks 12 and 20. The primary endpoint, an assessment of overall response rate (ORR) by week 28, was within the prespecified margin for Riabni compared to Rituxan, showing clinical equivalence. PK, PD, safety and immunogenicity of Riabni were similar to Rituxan.

Amgen has a total of 10 biosimilars in its portfolio, five of which have been approved in the U.S., and three that are approved in the European Union (EU).

About Riabni (rituximab-arrx) in the U.S.
Riabni is a biosimilar to Rituxan, an anti-CD20 monoclonal antibody. The active ingredient of Riabni is a monoclonal antibody that has the same amino acid sequence as Rituxan. Riabni also has the same strength as Rituxan, and the dosage form and route of administration are identical to the IV formulation of Rituxan.

Riabni (rituximab-arrx) is indicated for the treatment of adult patients with:
Relapsed or refractory, low-grade or follicular, CD20-positive, B-cell NHL as a single agent.
Previously untreated follicular, CD20-positive, B-cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to a rituximab product in combination with chemotherapy, as single-agent maintenance therapy.
Non-progressing (including stable disease), low-grade, CD20-positive, B-cell NHL as a single agent after first line cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy.
Previously untreated diffuse large B-cell, CD20-positive NHL in combination with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or other anthracycline-based chemotherapy regimens.