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.

The FDA approved the last specialty therapy for 2020 just in time for Christmas. The new oral drug, Orgovyx from four-year-old Myovant Sciences, is indicated for advanced prostate cancer.

The American Cancer Society estimates more than 190,000 cases of prostate cancer in the U.S. will have been diagnosed in 2020. Current treatment options for advanced prostate cancer includes androgen deprivation therapy, which uses drugs to lower levels of the hormones that help prostate cancer cells grow. Current FDA-approved treatments of this type are infused or placed as small implants under the skin. Orgovyx is a first-in-class, non-infused option for these patients. Analysts believe that patient concerns associated with COVID-19 exposure will drive Oncologists to prescribe an oral regimen vs. hospital or clinic infusions/implants.

The company plans to launch Orgovyx , a gonadotropin-releasing hormone antagonist, in January.

Orgovyx carries a list price of $2,313 per 30 tablet supply.
The approval of Orgovyx was another lump of coal in the Christmas stocking of specialty pharmacies nationally. Only a few select SPs will enjoy yet one additional limited distribution product this new year.

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Myovant scores FDA nod for Orgovyx, a first-in-class pill for advanced prostate cancer

Dec 21, 2020 — Myovant Sciences has its first FDA approval in Orgovyx, a new oral treatment for advanced prostate cancer. A once-daily pill, the new medicine could become an attractive option for patients looking to avoid in-person injections during the ongoing COVID-19 pandemic.

With the nod, advanced prostate cancer patients “now have a new oral treatment option that has demonstrated robust efficacy and safety, all with one pill taken once a day,” Myovant CEO Lynn Seely, M.D., said in a statement. The company plans to launch Orgovyx in January.

Aside from scoring a new drug approval, the company has “successfully built our commercial capabilities” and aims to make the treatment the new standard of care, Seely said.

In a phase 3 trial, investigators enrolled 934 men with advanced prostate cancer. Two-third received Myovant’s GnRH receptor antagonist, while the other third received depot injections of leuprolide, the standard of care for people undergoing androgen deprivation therapy.

In those who received the Myovant drug, testosterone was suppressed to castrate levels in 96.7% of patients from week five to week 48, compared with 88.8% for leuprolide acetate injections. The FDA requires new drugs to achieve suppression levels in 90% of patients for approval.

In a note Friday, Evercore ISI analyst Josh Schimmer wrote to clients that the label “reads pretty clean” and that his team’s communications with specialists revealed enthusiasm about the drug among prescribers.”

Aside from its initial approved use, Myovant is testing relugolix—the active ingredient in Orgovyx—as a combination tablet for uterine fibroids and endometriosis-associated pain.

December 29, 2020Winter Garden, FL

More catching up — The FDA approved another specialty therapy earlier this month. The new approval is Margenza (margetuximab-cmkb) from MacroGenics and is indicated for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens. It the first HER2-targeted therapy to have improved progression-free survival (PFS) versus Herceptin (trastuzumab), when both are combined with chemotherapy. Margenza is an infused therapy. Other 2020 approvals for HER2 breast cancer have been orals.Pricing was not announced at the time of approval.Product launch is targeted for March 2021. Because of its anticipated high cost and a black box warning, Margenza will likely launch as yet another distribution product via a specialty pharmacy, direct-to-office/hospital. MacroGenics Announces FDA Approval of Margenza  for Patients with Pretreated Metastatic HER2-Positive Breast Cancer ROCKVILLE, MD, Dec. 16, 2020 (GLOBE NEWSWIRE) — MacroGenics, Inc., a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, today announced that the U.S. Food and Drug Administration (FDA) has approved Margenza  , in combination with chemotherapy, for the treatment of adult patients with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Margenza is the first product approved from MacroGenics’ promising pipeline. The approval was based on safety and efficacy results from the pivotal Phase 3 SOPHIA trial. “The approval of Margenza….. Click here to read the full press release ——————– Anton RX Reports are copyrighted by Anton Health, LLC. ——————– Executive Editor William Sullivan wsullivan@AntonHealth.com For more information contact: Jim Larweth Anton Health 773-230-2525 AntonRxReport@AntonHealth.com www.AntonHealth.com

There really hasn’t been a lot of good news in the specialty pharmacy industry this year. Demand has been down due to the virus. Increasing DIR fees continue to bleed off profits. Virtually no FDA 2020 approvals will come to market in open access. But, the press release below from the National Association of Specialty Pharmacy (NASP) unwraps a gift under the 2020 specialty pharmacy Christmas tree.

Recently, the US Supreme Court issued an 8-0 decision confirming a state’s right to regulate the level of reimbursement by PBMs to specialty pharmacies. It has the effect of ensuring that specialty pharmacies should not be reimbursed at a rate lower than their actual acquisition cost. In short, pharmacies will not have to suffer an automatic loss on many prescriptions where the PBM arbitrarily sets reimbursement in RED levels. That is a BIG deal and the best gift that the industry could hope for at the close to a very challenging year.

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Specialty Pharmacy Applauds Supreme Court Decision to Allow States to Regulate PBM Practices

WASHINGTON, Dec. 11, 2020 /PRNewswire/ — The National Association of Specialty Pharmacy (NASP) applauds the 8-0 decision by the Supreme Court to restore Arkansas’ right to govern the amount that Pharmacy Benefit Managers (PBMs) reimburse pharmacies, in Rutledge v. the Pharmaceutical Care Management Association (PCMA). This decision will give states more flexibility to oversee PBM reimbursement practices to ensure patient access and affordability and protect market competition.

Since 2012, NASP members have reported a dramatic decrease in prescription reimbursement and an increase in claw-back fees such as Direct and Indirect Remuneration (DIR) by many PBMs.

“NASP is pleased with the Supreme Court’s unanimous ruling and believes this decision will protect states’ rights to oversee and control abusive practices. Reimbursements from PBMs that are below a specialty pharmacy’s cost threaten patient care and medication access. Specialty pharmacies provide critical care and services for patients living with cancer, rheumatoid arthritis, multiple sclerosis, cystic fibrosis, HIV/AIDS, and other chronic and complex diseases. Today’s decision is a key step in providing the oversight needed to ensure patients have access to the quality care that specialty pharmacies provide,” said Sheila M. Arquette, RPh, NASP President & CEO.”

Contact: Sheila M. Arquette, RPh, President & CEO, (703) 842-0122

The National Association of Specialty Pharmacy (NASP) is the only national association representing all stakeholders in the specialty pharmacy industry. NASP members include the nation’s leading specialty pharmacies, pharmaceutical and biotechnology manufacturers, group purchasing organizations, patient advocacy groups, integrated delivery systems and health plans, technology and data management vendors, wholesalers/distributors, healthcare providers, and practicing pharmacists. With over 130 corporate members and approximately 1,800 individual members, NASP is the unified voice of specialty pharmacy in the United States.

SOURCE National Association of Specialty Pharmacy

This year saw few specialty pharmacy acquisitions…. but that just changed with the announcement by Centene Corporation that it has acquired PantherRx Rare Pharmacy. Terms were not disclosed.

It is an important acquisition, but first, let’s look at Centene.
Centene Corporation is a large, publicly-traded, multi-line managed care enterprise that serves as a major intermediary for government-sponsored managed care plans for uninsured, underinsured, and low-income individuals. It also offers traditional, privately-insured health care programs.

Centene also contracts with other healthcare and commercial organizations to provide specialty services, including pharmacy benefits management (PBM), specialty pharmacy dispensing, mail service pharmacy, behavioral health care services, case management software, correctional insurance, in-home health services, life and health management, vision, and telehealth services. (Wikipedia).

Centene has a history of growth through acquisition in virtually all of these areas. One of its largest acquisitions happened in March 2019 when Centene acquired WellCare for $17 billion. Since the acquisition, Centene merged Exactus Pharmacy Solutions, WellCare’s specialty pharmacy, into Acaria Specialty Pharmacy which they previously acquired in January 2013.

As of 2020, Centene ranked as the largest provider of government-sponsored health plans with roughly 22 million members. Centene ranked No. 42 in the 2020 Fortune 500 list of the largest United States corporations by total revenue.

Centene announced earlier this month that it also acquired a data analytics firm, Apixio, to support its pharmacy and health management operations, to expand Centene’s existing data analytics, and create the ability to document value-based payments. Value-based contracting, already a proof of concept, is thought to be a critical element to payer coverage of ultra-high cost specialty therapies (e.g., rare drugs) in coming years.

Centene and Specialty Pharmacy —–
Centene took its first deep dive into specialty pharmacy with the acquisition of Acaria Health, a specialty pharmacy in Orlando, FL. for $152million (a bargain price by today’s standards).

The announcement that Centene was doubling down on specialty pharmacy with the PantherRx deal should not be surprising given Centene’s robust acquisition history. PantherRx is a ripe acquisition. PantherRx was ranked as the 12th largest specialty pharmacy in 2019 with $1.2billion in sales. That is a big hunk of revenue and, in combination with the Acaria specialty pharmacy revenue, creates huge clout in the marketplace especially with manufacturers.

Manufacturers are key to fueling PantherRx’s revenue engine. PantherRx opened doors only in 2011 and grew rapidly with an aggressive marketing strategy pursuing new, limited-distribution drugs. These LD deals funneled thousands of new prescriptions to their doors.

PantherRx rebranded themselves in 2019 as PantherRx RARE to reinforce a niche in the exploding orphan drug / genetic therapy market. In 2020, virtually every FDA specialty drug approval has or will come to market through limited distribution. That’s called being in the right place at the right time.

Acaria has operated seamlessly in the marketplace under its original name since the Centene acquisition. Centene has announced that PantherRx Rare will also operate under current management and retain its name…. at least for the time being. Given the pull that the PantherRx name generates, Centene is smartly taking an “ain’t broke, don’t fix it approach”.

So, in closing, think about the bigger picture.

Over the past few years payers have taken the lead in owning/operating specialty pharmacies. We don’t know final numbers for 2020 but the top of the leaderboard includes the following payers: CVS/Aetna, CIGNA/ESI-Accredo, UHC/OptumRx, Humana, and now Centene. One might call that a trend, one that may soon reshape the PBM and specialty markets in unprecedented ways.

Centene Signs Definitive Agreement to Acquire PANTHERx Rare Pharmacy (PANTHERx)

ST. LOUIS, Dec. 15, 2020 /PRNewswire/ — Centene Corporation today announced it has signed a definitive agreement to acquire PANTHERx, one of the largest and fastest-growing specialty pharmacies in the United States specializing in orphan drugs and rare diseases. The transaction is subject to regulatory approvals and is expected to close by the end of 2020.

PANTHERx is a leader in rare disease pharmacy, comprehensively serving patients afflicted with rare and devastating conditions through delivery of medicine breakthroughs, clinical excellence, and access solutions. PANTHERx offers a suite of synchronized compliance, logistics, and analytics solutions to help streamline the process of delivering orphan medications and care to people living with complicated rare diseases.

“Centene has a long-standing commitment to providing care to the most underserved, complex populations,” said Michael F. Neidorff, Chairman, President and Chief Executive Officer for Centene. “PANTHERx adds a unique capability to our comprehensive pharmacy portfolio. We share a common goal of helping to remove barriers and reduce the burden for our members living with complex and rare diseases.”

“We are elated to enter a partnership that will propel us to the next level and provide opportunities for growth and stability while fostering an independence that delivers greater benefits to our patients, partners and associates,” stated Dr. Gordon J. Vanscoy, founder and CEO of PANTHERx. “Centene has committed to nurturing our patient-centric culture and focus on quality that is fundamental to PANTHERx’s tremendous success.”

PANTHERx and its management team will continue to operate independently as part of Centene’s Envolve Pharmacy Solutions, a total drug management program that includes integrated Pharmacy Benefit Manager (PBM) services and specialty pharmacy solutions to millions of members throughout the United States.

Someone must have lit a fire under the FDA new drug approval elves in the last few weeks as the activity level there suddenly boomed. There will be a lot of catch up to cover all the news in coming weeks.

In late November the FDA approved one of the very few new Biologics in 2020. The approval was for Danyelza (naxitamab) from Y-mAbs Therapeutics. The indication was for infusion in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for pediatric and adult patients with relapsed or refractory high-risk neuroblastoma.

Each year, about 800 children age 0 to 14 are diagnosed with neuroblastoma in the United States. It accounts for 6% of all childhood cancers in the United States. Almost 90% of neuroblastoma is found in children younger than 5.

Danyelza received an orphan drug designation as well as a priority review voucher for their rare pediatric disease product application. Pricing for Danyelza has still not yet been released. The MagellanRx Pipeline Report (October 2020) forecasts that the therapy will only generate $27 million in 2021 ramping up to $165 million in 2024….. small potatoes compared with some of the other 2020 approvals.

Given that Danyelza serves a very small patent population and a course of therapy will be costly, we expect that Danyelza will come to market as a distribution item, direct-to-infusion site, through a specialty pharmacy.

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FDA grants accelerated approval to naxitamab for high-risk neuroblastoma in bone or bone marrow

On November 24, 2020, the Food and Drug Administration granted accelerated approval to naxitamab (DANYELZA, Y-mAbs Therapeutics, Inc.) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) for pediatric patients one year of age and older and adult patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow demonstrating a partial response, minor response, or stable disease to prior therapy.

Efficacy was evaluated in patients with relapsed or refractory neuroblastoma in the bone or bone marrow enrolled in two single-arm, open-label trials: Study 201 (NCT 03363373) and Study 12-230 (NCT 01757626). Patients with progressive disease following their most recent therapy were excluded. Patients received 3 mg/kg naxitamab administered as an intravenous infusion on days 1, 3, and 5 of each 4-week cycle in combination with GM-CSF subcutaneously at 250 µg/m2/day on days -4 to 0 and at 500 µg/m2/day on days 1 to 5. At the investigator’s discretion, patients were permitted to receive pre-planned radiation to the primary disease site in Study 201 and radiation therapy to non-target bony lesions or soft tissue disease in Study 12-230.

The main efficacy outcome measures were confirmed overall response rate (ORR) per the revised International Neuroblastoma Response Criteria (INRC) and duration of response (DOR). Among 22 patients treated in the multicenter Study 201, the ORR was 45% (95% CI: 24%, 68%) and 30% of responders had a DOR greater or equal to 6 months. Among 38 patients treated in the single-center Study 12-230, the ORR was 34% (95% CI: 20%, 51%) with 23% of patients having a DOR greater or equal to 6 months. For both trials, responses were observed in either the bone, bone marrow or both.

The prescribing information contains a Boxed Warning stating that naxitamab can cause serious infusion-related reactions and neurotoxicity, including severe neuropathic pain, transverse myelitis and reversible posterior leukoencephalopathy syndrome (RPLS). To mitigate these risks, patients should receive premedication prior to each naxitamab infusion and be closely monitored during and for at least two hours following completion of each infusion.

The most common adverse reactions (incidence ≥25% in either trial) in patients receiving naxitamab were infusion-related reactions, pain, tachycardia, vomiting, cough, nausea, diarrhea, decreased appetite, hypertension, fatigue, erythema multiforme, peripheral neuropathy, urticaria, pyrexia, headache, injection site reaction, edema, anxiety, localized edema, and irritability. The most common Grade 3 or 4 laboratory abnormalities (≥5% in either trial) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased platelet count, decreased potassium, increased alanine aminotransferase, decreased glucose, decreased calcium, decreased albumin, decreased sodium and decreased phosphate.

The recommended naxitamab dose is 3 mg/kg/day (up to 150 mg/day) on days 1, 3, and 5 of each treatment cycle, administered after dilution as an intravenous infusion in combination with GM-CSF, subcutaneously at 250 µg/m2/day on days -4 to 0 and at 500 µg/m2/day on days 1 to 5. Treatment cycles are repeated every 4 to 8 weeks.

This application was granted accelerated approval based on overall response rate and duration of response. Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials.

This application was granted priority review, breakthrough therapy, and orphan drug designation. A priority review voucher was issued for this rare pediatric disease product application. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

We ran across a press release recently that looked a tad odd. It appeared that the FDA had approved a new therapy, Alkindi Sprinkle from Eton Pharma indicated as replacement therapy in pediatric patients with adrenocortical insufficiency (AI). But, this drug wasn’t appearing on any market reports for a pending new drug approval. Furthermore, the press release detailed that the drug was going into exclusive distribution via specialty pharmacy. Hmmmmmmm. A few minutes of internet sleuthing assuaged my confusion. It turns out that the approval was for a new formulation of a drug originally approved in 1952!!

But let’s look deeper into whether this drug qualifies as a specialty pharmacy item. We checked GoodRx and found that the cash price with coupon is as low as $215 for a month’s supply.
Whaaaaat????? That can’t be right. But it is.

So, does low price disqualify Alkindi Sprinkle as a specialty pharmacy product? Price has always been a wild card to determine if a drug is counted as a specialty product. But, throw in an Orphan Drug designation (AI affects between 5,000 and 11,000 children in the US) and the consensus has to lean towards awarding this drug a seat at the specialty pharmacy table. Don’t ya think?

This may help explain why Eton has placed it into limited distribution. The new formulation of Alkindi Sprinkle is a low dose oral granule option for children who, since 1952, were forced to rely on adult-strength hydrocortisone tablets to treat adrenocortical insufficiency. Low-dose options now allow for more accurate and individualized dosing for these kids. While there is no black box on the label, there are a few general warnings and precautions that might be of greater concern in children….. adding to the argument for going LD.

Alkindi Sprinkle is exclusively available through AnovoRx Specialty Pharmacy, yet another specialty pharmacy that is rebranding itself as a rare disease pharmacy.

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Availability of Orphan Drug Alkindi Sprinkle (hydrocortisone) in the United States

DEER PARK, Ill., (GLOBE NEWSWIRE) — Eton Pharmaceuticals, Inc (Nasdaq: ETON), a specialty pharmaceutical company focused on developing and commercializing innovative treatments for rare pediatric diseases, today announced the full availability of Alkindi Sprinklefor sale and distribution in the United States. The U.S. Food and Drug Administration (FDA) has approved Alkindi Sprinkle (hydrocortisone) oral granules as replacement therapy for Adrenocortical Insufficiency (AI) in children under 17 years of age. Alkindi Sprinkle is the first and only FDA-approved granular hydrocortisone formulation for the treatment of adrenocortical insufficiency specifically designed for use in children.

Alkindi Sprinkle will be available exclusively through AnovoRx, a specialty pharmacy dedicated to serving patients with rare and chronic conditions. AnovoRx will administer the Eton Cares Program in partnership with Eton Pharmaceuticals. The program will complete prescription fulfillment, insurance benefits investigation, educational support, aid qualified patients to obtain financial assistance along with other services designed to help patients access treatment. To enroll patients in the program and prescribe Alkindi Sprinkle, clinicians will need to complete a patient referral form available at www.alkindisprinkle.com.

The FDA approval of Alkindi Sprinkle was supported by six clinical studies, including the first and only interventional Phase III study of oral hydrocortisone for Pediatric AI in neonates to children under eight years of age. Alkindi Sprinkle achieved significant increases in cortisol levels from baseline (P<0.0001) and was found to be well tolerated with no serious adverse events. Prior to the approval of Alkindi Sprinkle, oral hydrocortisone was only FDA-approved in tablet formulations of 5 mg and stronger. Many pediatric patients require significantly lower doses and the flexibility of precision titration. Alkindi Sprinkle will be available in 0.5-mg, 1-mg, 2-mg, and 5-mg strengths, allowing clinicians greater flexibility to individualize dosing based on each patient’s needs in accordance with the instructions for dosage and administration.

About Alkindi Sprinkle
Alkindi Sprinkle is an immediate-release oral hydrocortisone granule preparation that has been specifically designed to meet the dosing needs of pediatric patients with adrenocortical insufficiency. Prior to Alkindi Sprinkle’s approval, parent caregivers have had to cut or split higher-strength hydrocortisone tablets to achieve the lower doses required for small children, which could result in inaccurate dosing. Alkindi Sprinkle is manufactured using commercially proven technology in four strengths: 0.5 mg, 1 mg, 2 mg and 5 mg, to give greater dosing flexibility to clinicians. Taste-masking excipients that are acceptable for pediatric use eliminate the bitter taste of hydrocortisone. Alkindi Sprinkle has a shelf -life of three years at ambient temperature and does not require refrigeration.

Earlier this month the FDA approved yet another orphan drug, Orladeyo (berotralstat) from BioCryst Pharmaceuticals. It obtained an indication for the prevention of hereditary angioedema (HAE) attacks. Orladeyo is the first oral, non-biologic, once daily treatment for this condition.

HAE is caused by a genetic defect causing a biochemical imbalance that releases fluids outside of the blood vessels into surrounding tissues. Symptoms include swelling in various parts of the body, including the hands, feet, face and airway. Airway swelling can lead to death by asphyxiation. Before therapies became available, the mortality rate for airway obstruction was as high as 30%. HAE defect interferes with a blood protein (called C1 inhibitor) that helps to regulate blood-based systems involved in disease fighting, inflammation and coagulation.

Only 7,500 people are diagnosed and treated for HAE in the U.S.

Rare conditions are usually lucky to have a single novel therapy for patients. HAE is remarkably different as it has eight….. yep, eight brands to choose from. They include Berinert, Cinryze, Firazyr, Haegarda, Kalbitor, Orladeyo, Ruconest, Takhzyro. Oh, and a few days after the approval of Orladeyo the FDA approved a generic version of Firazyr. The more the merrier??

Orladeyo is a relatively late market entry and will compete with these well-established therapies. Leading competitive therapies include Cinryze and Haegarda, and Takhzyro. However, Cinryze requires intravenous (IV) administration, Haegarda is administered via subcutaneous injection every 3 to 4 days and Takhzyro is SC administered every 2 to 4 weeks. Orladeyo has the advantage of being the first oral formulation.

Specific pricing for Orladeyo was just announced. Many analysts believed that the non-biologic Orladeyo could be priced less than the biologic alternatives currently in use. But NO! Biocryst set the wholesale acquisition cost at $485,004 annually, or $37,308 per 28-day pack of either 150-mg or 110-mg capsules. By comparison, the WAC price for Takhzyro is ~$591,000 per year.

Biocryst announced that it has selected Optime Care Inc. as the exclusive ‘rare disease’ specialty pharmacy provider for Orladeyo. Patient shipments from Optime Care are expected to begin by the end of December.

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BioCryst Announces FDA Approval of Orladeyo™ (berotralstat), First Oral, Once-daily Therapy to Prevent Attacks in Hereditary Angioedema Patients

RESEARCH TRIANGLE PARK, N.C., Dec. 03, 2020 (GLOBE NEWSWIRE) — BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) today announced that the U.S. Food and Drug Administration (FDA) has approved oral, once-daily Orladeyo™ (berotralstat) for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adults and pediatric patients 12 years and older.

“Orladeyo offers people with HAE and their physicians the first orally administered non-steroidal option for preventing HAE attacks and represents an important and welcome step in making more treatment options available to physicians and patients,” said Anthony J. Castaldo, president and chief executive officer of………

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