Author: Randy Chase

Just before Thanksgiving the FDA approved a new ORAL therapy, Livtencity (maribavir) from Takeda Pharmaceuticals, with an indication for the treatment of adults and pediatric patients (12 years of age and older and weighing at least 35 kg) with post-transplant cytomegalovirus (CMV) infection/disease that is refractory to treatment (with or without genotypic resistance) with ganciclovir, valganciclovir, cidofovir or foscarnet.

Post-transplant cytomegalovirus (CMV) is a rare disease and is one of the most common infections experienced by transplant recipients. The incidence rate varies by specific diagnosis with 16-56 % in Solid Organ Transplant (SOT) recipients and 30-70 % in Hematopoietic Stem Cell Transplant (HSCT) patients.

Takeda has not yet released the cost of Livtencity.

Takeda subsequently announced that the therapy will be available only through a select network of specialty pharmacies and distributors.

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FDA Approves First Treatment for Common Type of Post-Transplant Infection that is Resistant to Other Drugs

November 23, 2021 — Today, the U.S. Food and Drug Administration approved Livtencity (maribavir) as the first drug for treating adults and pediatric patients (12 years of age and older and weighing at least 35 kilograms) with post-transplant cytomegalovirus (CMV) infection/disease that does not respond (with or without genetic mutations that cause resistance) to available antiviral treatment for CMV. Livtencity works by preventing the activity of human cytomegalovirus enzyme pUL97, thus blocking virus replication.

“Transplant recipients are at a much greater risk for complications and death when faced with a cytomegalovirus infection,” said John Farley, M.D., M.P.H., director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research. “Cytomegalovirus infections that are resistant or do not respond to available drugs are of even greater concern. Today’s approval helps meet a significant unmet medical need by providing a treatment option for this patient population.”

CMV is a type of herpes virus that commonly causes infection in patients after a stem cell or organ transplant. CMV infection can lead to CMV disease and have a major negative impact on transplant recipients, including loss of the transplanted organ and death.

Livtencity’s safety and efficacy were evaluated in a Phase 3, multicenter, open-label, active-controlled trial that compared Livtencity with a treatment assigned by a researcher running the study, which could include one or two of the following antivirals used to treat CMV: ganciclovir, valganciclovir, foscarnet or cidofovir. In the study, 352 transplant recipients with CMV infections who did not respond (with or without resistance) to treatment randomly received Livtencity or treatment assigned by a researcher for up to eight weeks.

The study compared the two groups’ plasma CMV DNA concentration levels at the end of the study’s eighth week, with efficacy defined as having a level below what is measurable. Of the 235 patients who received Livtencity, 56% had levels of CMV DNA below what was measurable versus 24% of the 117 patients who received an investigator-assigned treatment.

The most common side effects of Livtencity include taste disturbance, nausea, diarrhea, vomiting and fatigue. Livtencity may reduce the antiviral activity of ganciclovir and valganciclovir, so coadministration with these drugs is not recommended. Virologic failure due to resistance can occur during and after treatment with Livtencity, therefore CMV DNA levels should be monitored and Livtencity resistance should be checked if the patient is not responding to treatment or relapses.

Livtencity received Breakthrough Therapy and Priority Review designations for this indication. Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s). Priority Review designation directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions when compared to standard applications.

The FDA granted the approval of Livtencity to Takeda Pharmaceuticals Company Limited.

Last week the FDA approved a new infused therapy, Fyarro (sirolimus protein-bound particles for injectable suspension / albumin-bound) from Aadi Bioscience, for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa).

Fyarro is the first and only approved therapy for adults with this condition, an ultra-rare and aggressive form of sarcoma with a strong female predominance. Malignant PEComas may arise in almost any body site (typically the uterus, retroperitoneum, lung, kidney, liver, genitourinary, and gastrointestinal tract.

It is estimated that there are only about 100-300 new patients per year in the United States.

Fyarro’s wholesale acquisition cost was announced at $6,785.00 for a single-use 100 milligram vial. Utilization is dependent on the patient’s body mass and any dosing modification resulting in a cost of approximately $468,000 per year. Aadi said that “Discounts, such as Medicaid rebates, sales to 340B covered entities and VA facilities among others, will reduce the net price by approximately 15% to 20%.”

Given the small patient population in the US it is expected that Fyarro will be launched through a specialty pharmacy distribution (direct to physician) program.

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Aadi Bioscience Announces FDA Approval of its First Product FYARRO for Patients with Locally Advanced Unresectable or Metastatic Malignant Perivascular Epithelioid Cell Tumor (PEComa)

LOS ANGELES, Nov. 23, 2021 — Aadi Bioscience, Inc., a biopharmaceutical company focusing on precision therapies for genetically-defined cancers with alterations in mTOR pathway genes, today announced that the U.S. Food and Drug Administration (FDA) has approved FYARRO™ (sirolimus protein-bound particles for injectable suspension) (albumin-bound) for intravenous use for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). FYARRO is the first and only FDA-approved treatment for advanced malignant PEComa in adults.

Neil Desai, Ph.D., Founder, Chief Executive Officer and President of Aadi, stated, “We are thrilled to have received full FDA-approval of FYARRO. The approval of FYARRO is a momentous event not just for Aadi but, importantly for advanced malignant PEComa patients. We reiterate that all of us at Aadi are incredibly grateful to all of the people with advanced malignant PEComa, their families and caregivers, as well as the healthcare professionals who made the FYARRO clinical studies possible.”

“The approval of FYARRO, the first approved drug for advanced malignant PEComa, an aggressive sarcoma with a poor prognosis and few treatment options, will provide physicians with a new weapon for treating patients with this rare disease,” added Andrew Wagner, M.D., Ph.D., a senior oncologist at Dana-Farber Cancer Institute and the Principal Investigator in the pivotal AMPECT registrational trial. “In our AMPECT trial, FYARRO demonstrated durable responses in mTOR inhibitor-naïve patients with locally advanced unresectable or metastatic PEComa, with an acceptable and manageable safety profile. This is a drug that will be welcomed by the physician community as the only approved therapeutic option for patients with advanced malignant PEComa.”

In the Phase 2 registrational AMPECT trial the overall response rate as assessed by independent review was 39% (12/31) with 2 patients achieving a Complete Response after prolonged follow up. The median duration of response has not been reached with a median follow-up of 36 months, and a range of 5.6 to 55.5+ months and ongoing. Among responders, 92% had a response lasting greater than or equal to 6 months; 67% had a response lasting greater than or equal to 12 months; and 58% had a response lasting greater than or equal to 2 years. As is the case with other therapeutics of the mTOR class, the FYARRO prescribing information includes warnings and precautions related to stomatitis, myelosuppression, infections, hypokalemia, hyperglycemia, interstitial lung disease, hemorrhage, and hypersensitivity reactions. Grade 3 non-hematologic events occurring in more than 10% of patients included stomatitis, rash, fatigue and infections. Grade 3 laboratory abnormalities occurring in more than 10% of patients that worsened from baseline included lymphocytopenia, increased glucose, and decreased potassium. For detailed important safety information, please see below.

Brendan Delaney, Chief Operating Officer of Aadi, added, “We have built a strong commercial team and devised a thoughtful strategy in preparation for FYARRO’s launch. With FYARRO’s demonstrated clinical profile we believe it will become a standard of care for advanced malignant PEComa. We look forward to engaging with physicians to educate the market about this new treatment.”

About Malignant PEComa
Advanced malignant PEComa, defined by the World Health Organization as ‘mesenchymal tumors composed of distinctive cells that show a focal association with blood-vessel walls and usually express both melanocytic and smooth muscle markers,’ are a rare subset of soft-tissue sarcomas, with an undefined cell of origin. While there is no formal epidemiology for malignant PEComa, with a female predominance) and can have an aggressive clinical course including distant metastases and ultimately death. The estimated prognosis based on retrospective reports is 12-16 months. Cytotoxic chemotherapies typically used for sarcoma show minimal benefit and there are currently no drugs approved for this disease. Malignant PEComas have been shown to frequently harbor mutations in the TSC1 and/or TSC2 genes that result in the activation of mTOR pathway making it a rational therapeutic target for this disease.

I’ve editorialized about the encroachment of health system owned specialty pharmacies (HOSPs) into the independent SP space since 2013. Each prescription that is directed ‘in-system’ is a prescription that doesn’t go to an independent…. or even a big box SP.

Consider the article below. One key line reads….. “there hasn’t been one organization that represents all the interests of the industry in one place.”

It is curious that the HOSP Alliance feels that the HOSP segment voice is not now being adequately represented. You may, however, get a different view by visiting the NASP web site. As most of us know, NASP is one organization that has represented all the interests of the SP industry for years. But, the fastest growing NASP segment (based on a quick count of corporate sponsors on the NASP site) appears to be, you may have guessed it, health system owned specialty pharmacies. Upwards of 30 health systems are current NASP sponsors, including Shields/ExceleraRx and TrellisRx (companies that have led the charge to form HOSPs). That’s more than 20% of all NASP sponsors!

So, ask yourself….. “Why does the HOSP Alliance feels that it now needs its own ‘industry’ voice?”

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How a health system alliance is advocating for hospital-owned specialty pharmacies

In October 2020, seven health systems united to form the Health System Owned Specialty Pharmacy Alliance, or HOSP, to advocate for health system-owned specialty pharmacies.

The group has grown significantly since its launch, with nearly 30 health systems now participating. Here, Gary Kerr, PharmD, the president of HOSP’s board of directors and the chief pharmacy officer at Springfield, Mass.-based Baystate Health, answers questions about the group’s work and plans.

Editor’s note: Responses have been lightly edited for clarity and style.

Q: Why do health system-owned specialty pharmacies need their own voice?
Dr. Gary Kerr: HOSP acts as the “face and voice” of the integrated specialty pharmacy industry, advocating for and uniting members around common industry interests and concerns. The industry needs its own voice because while there are several organizations that represent many general interests impacting health system specialty pharmacy, there hasn’t been one organization that represents all the interests of the industry in one place. Our goal is to help bring the industry together, so health system-owned specialty pharmacies have a seat at the table and ensure that their interests are represented. That said, we recognize there is some great work underway by other organizations, and we don’t intend to duplicate efforts. Rather, we are supportive of that work and intend to focus on the areas where there are gaps.

Specialty pharmacies focus on delivering medications for more complex and chronic illnesses. More than 1 in 4 specialty pharmacies are now owned by health systems, a trend that is continuing to grow as hospitals look for ways to improve patient care. The integrated specialty pharmacy model helps keep a critical piece of patient care — medication management and treatment — inside the health system, instead of outsourcing to a more fragmented approach to care. From a physical plant perspective alone many of these system-owned specialty pharmacies operate on campus along with the clinicians’ offices, share the electronic medical record with the prescribers and control all aspects of the land-based courier services.

Q: How many health systems are involved in HOSP?
GK: We had a great first year, and membership has increased significantly year over year. We currently have nearly 30 health systems participating, and we are growing fast. We also unveiled an active campaign this fall, now underway, to identify and embrace new partnerships beyond the core of the health system specialty pharmacy members. The HOSP Partnership Program offers a unique way for like-minded organizations to collaborate with and support our industry.

Q: What does HOSP’s collaboration with health systems look like?
GK: We don’t collaborate with health systems, but rather our membership is composed of health systems who are generally represented by their system’s integrated specialty pharmacy leadership. Members actively and thoughtfully collaborate to share emerging best practices, discuss innovative work processes and patient care solutions and develop and advance a unified voice on a variety of policy issues. Members are also focused on full engagement on how to demonstrate and share the value of the integrated specialty pharmacy model, by shaping the metrics data aspect of the care model.

Q: What have been HOSP’s biggest accomplishments since its launch?
GK: HOSP has done a lot in one year. We’ve established a very strong board of directors and have been steadily increasing our membership base. We have four dedicated hardworking committees. One is the innovation committee; whose goal is to increase awareness and influence actions to improve quality of care and patient outcomes with improved patient management software integration in health systems-owned specialty pharmacies. They have dug deeply into the patient journey to find where there are gaps that technologies and other solutions could help address. We’ll be highlighting them more in the near future.

Another committee you’ll be hearing about is our Health Economics and Research Outcomes committee, which owns HOSP’s work to develop and collaborate on the most valuable data (metrics) that helps promote the value of the integrated, specialty pharmacy care model. Our advocacy committee just sent a letter introducing HOSP and outlining our top priorities to HHS Secretary Xavier Becerra and top congressional officials.

We’ve also made some great inroads in beginning some new initiatives that we’ll be advancing in 2022, including our HOSP best practice groups, which bring leaders across membership together to share best practices on a variety of issues.

Q: What initiatives does HOSP have planned for the future?
GK: In addition to growing our membership and keeping our committees focused on the great work we are producing. We’re planning an in-person member event in early 2022. Since we launched during the COVID-19 pandemic, we have yet to get together in person, so we’re very excited to finally get together in the same space.

Last week the FDA approved a new subcutaneous therapy, Voxzogo (vosoritide) from BioMarin, to improve growth in children five years of age and older with achondroplasia, the most common form of dwarfism, as well as open epiphyses (growth plates).

Achondroplasia is the most common type of short-limbed dwarfism, with a global incidence of 1 in 15,000 to 40,000 newborns. Most cases are not inherited, but rather result from new mutations (80%) in the FGFR3 gene causing abnormal formation of cartilage and bone and ultimately shorter bones; however, if both parents have achondroplasia, then there is a 50% chance that their children will be affected.

Voxzogo is an analog of C-type natriuretic peptide (CNP), a positive regulator of bone growth. Vosoritide also inhibits fibroblast growth factor receptor 3 (FGFR3), which has a negative effect on bone growth. Vosoritide has a longer half-life than its endogenous form. Across the trial studies, vosoritide was generally well tolerated, with transient injection site reactions and hypotension as the most common TEAEs.

BioMarin announced that the list price per year will run $320,000 per year. After rebates and discounts, Voxzogo will net about $240,000 per patient per year. Given the low incidence of the indicated conditions, it is expected that the therapy will launch in limited distribution.

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FDA Approves First Drug to Improve Growth in Children with Most Common Form of Dwarfism

SILVER SPRING, Md., Nov. 19, 2021 /PRNewswire/ — Today, the U.S. Food and Drug Administration approved Voxzogo (vosoritide) injection to improve growth in children five years of age and older with achondroplasia and open epiphyses (growth plates), meaning these children still have the potential to grow. Achondroplasia is the most common form of dwarfism.

“Today’s approval fulfills an unmet medical need for more than 10,000 children in the United States and underscores the FDA’s commitment to help make new therapies available for rare diseases,” said Theresa Kehoe, M.D., director of the Division of General Endocrinology in the FDA’s Center for Drug Evaluation and Research. “With this action, children with short stature due to achondroplasia have a treatment option that targets the underlying cause of their short stature.”

Achondroplasia is a genetic condition that causes severely short stature and disproportionate growth. The average height of an adult with achondroplasia is approximately four feet. People with achondroplasia have a genetic mutation that causes a certain growth regulation gene called fibroblast growth factor receptor 3 to be overly active, which prevents normal bone growth. Voxzogo works by binding to a specific receptor called natriuretic peptide receptor-B that reduces the growth regulation gene’s activity and stimulates bone growth.

Voxzogo’s safety and efficacy in improving growth were evaluated in a year-long, double-blind, placebo-controlled, phase 3 study in participants five years and older with achondroplasia who have open epiphyses. In the study, 121 participants were randomly assigned to receive either Voxzogo injections under the skin or a placebo. Researchers measured the participants’ annualized growth velocity, or rate of height growth, at the end of the year. Participants who received Voxzogo grew an average 1.57 centimeters taller compared to those who received a placebo.

The most common side effects of Voxzogo include injection site reactions, vomiting and decreased blood pressure. Voxzogo’s labeling also lists decreased blood pressure as a warning and precaution, which means it is a potentially serious side effect.

The FDA approved Voxzogo under the accelerated approval pathway, which allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need, based on a surrogate or intermediate clinical endpoint. A condition of this accelerated approval is a post-marketing study that will assess final adult height. This application also received priority review designation.

The FDA granted the approval of Voxzogo to BioMarin.

Specialty pharmacies do a fair amount of business with Medicaid. In many states the Medicaid program allows any willing provider access, sometimes across state lines. The downside is that reimbursement margins may be very thin for the pharmacy. None the less, one element of sustaining any business is cash flow. Even with thin margins, Medicaid sales can be a reliable cash flow generator. As such, keeping an eye on trends in the Medicaid universe is a prudent business practice.

Magellan Rx recently published a nifty analysis for your reading pleasure. It details trends over the past few years. Knowing where the trends are heading can help with allocating resources to build new referral relationships, tweak operational / service planning, and more. The report also includes a bunch of useful charts and graphs.

Key 2020 findings include:

• In 2020, specialty drugs accounted for 51.4% of the net cost in Medicaid
• Specialty drugs only accounted for 1.3% of utilization.
• Traditional net cost trend for Medicaid FFS was positive for the first time in five years driven by new-to-market drugs.
• Medicaid FFS top drug classes remained almost identical to previous years
• HIV/AIDS and antipsychotics accounting for more than 19.8% of the total net drug spend.
• Most key conditions will experience increased trend over the next three years. 
• Conditions with generic drug introductions or specialized management strategies will trend lower.
• The 2020 virus impacted patient continuity of care triggering technology-based solutions (e.g., video conferencing, shift to home care, and more).

CLICK HERE to access the full Magellan report.
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Long Predicted Medicaid Specialty Drug Trend Finally Surpasses 50% of Pharmacy Spend in the Latest Magellan Rx Management Medicaid Pharmacy Trend Report

November 15, 2021  — PHOENIX–(BUSINESS WIRE)– Magellan Rx Management, the full-service pharmacy benefits management division of Magellan Health, Inc. (NASDAQ: MGLN), released its sixth annual Medicaid Pharmacy Trend ReportTM, the industry’s leading report exclusively detailing trends in the Medicaid pharmacy fee-for-service (FFS) space.

The Medicaid Pharmacy Trend Report highlights the evolving landscape of Medicaid, made even more dynamic from the events of the last two years. The report includes an in-depth analysis of class and drug trends, forecasting of Medicaid key conditions, drugs in the pipeline, and Medicaid pharmacy economics. This is also the only detailed industry source for the analysis of Medicaid pharmacy fee-for-service (FFS) gross, net, and forecasted drug cost trends.

“As our nation continues to navigate the lasting impacts of the COVID-19 pandemic, there is no doubt that states are facing unprecedented challenges across all areas of government, especially related to ensuring the mental and physical well-being of their citizens,” said Meredith Delk, PhD, MSW, general manager and senior vice president, government markets, Magellan Rx Management. “The Medicaid Trend Report illustrates critical data-driven observations and solutions. The valuable insights in this report can assist states on their mission to ensure a high quality and cost-effective prescription drug program for their most vulnerable populations.”

“Our ability to offer comprehensive and configurable solutions that fundamentally connect the dots for our customers and their members around the efficacy of drugs, quality care and payments is key,” said Delk.

The Magellan Rx Management Medicaid Pharmacy Trend Report includes data from Magellan Rx’s Medicaid FFS pharmacy programs in 25 states and the District of Columbia. The material is reviewed and supported by a team of Magellan Rx experts with broad national expertise, including 369 years of combined pharmacy benefit administration (PBA) experience.

Last week the FDA approved a new therapy, BESREMi (ropeginterferon alfa-2b-njft) from PharmaEssentia, for the treatment of adults with polycythemia vera (PV). The drug was granted an orphan designation. BESREMi is administered subcutaneously.

Polycythemia Vera (PV) is a cancer that originates from a disease-initiating stem cell in the bone marrow leading to a chronic increase of red blood cells, white blood cells, and platelets. The cancer then frequently results in cardiovascular complications as well as secondary myelofibrosis or leukemia.

BESREMi is a long-acting interferon and is administered once every two weeks until hematologic targets are realized. Patients with a complete hematologic response can then be treated every four weeks.

Analysts expect the annual cost per patient per year (PPPY) to be in the $40,000 range. Details related to channel access were not released. As an orphan drug, BESREMi will very likely be released through limited distribution.

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U.S. FDA Approves BESREMi (ropeginterferon alfa-2b-njft) as the Only Interferon for Adults With Polycythemia Vera

November 12, 2021 — BURLINGTON, Mass.–(BUSINESS WIRE)–PharmaEssentia Corporation (TPEx: 6446), a global biopharmaceutical innovator based in Taiwan leveraging deep expertise and proven scientific principles to deliver new biologics in hematology and oncology, today announced that the U.S. Food and Drug Administration (FDA) has approved BESREMi for the treatment of adults with polycythemia vera (PV).

“With the availability of an FDA-approved, next-generation interferon for this indication, it’s time that we focus on preserving the long-term health of patients with polycythemia vera.”

BESREMi is an innovative monopegylated, long-acting interferon, which exhibits its cellular effects in polycythemia vera in the bone marrow. BESREMi was approved with a boxed warning for risk of serious disorders including aggravation of neuropsychiatric, autoimmune, ischemic and infections disorders. PharmaEssentia is preparing to make BESREMi available in the coming weeks in the U.S.

“The FDA approval of BESREMi for people with polycythemia vera represents the next step in advancing patient care as it provides a critical addition to managing not only symptom burden and near-term complications, but also treating the cancer early, which may help reduce the risk of disease progression over time,” said Srdan Verstovsek, M.D., Ph.D., Director of the Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasms, Department of Leukemia at the University of Texas MD Anderson Cancer Center. “With the availability of an FDA-approved, next-generation interferon for this indication, it’s time that we focus on preserving the long-term health of patients with polycythemia vera.”

“The reality of living with a rare and chronic cancer like polycythemia vera is that it is often under recognized and the limited treatments available cannot properly address the disease beyond the symptoms. Our community welcomes the FDA approval of a new treatment that has the potential to deliver what has been unavailable for so many patients hoping for a better outlook,” said Ann Brazeau, CEO of MPN Advocacy and Education International.

The U.S. FDA approval was based on safety from the PEGINVERA and PROUD/ CONTINUATION-PV studies and efficacy data from the PEGINVERA clinical study program. The study showed that after 7.5 years of treatment with BESREMi, 61% of patients with PV experienced a complete hematological response (defined as hematocrit <45% without phlebotomy for at least 2 months since last phlebotomy, platelets ≤ 400 x 109/L, leukocytes ≤10 x 109/L, normal spleen size (longitudinal diameter ≤12 cm for females and ≤ 13 cm for males). Importantly, 80% of patients achieved a hematological response (based on objective laboratory parameters only, with the exclusion of normal spleen size and thrombosis). These parameters are the most commonly used metrics to make therapeutic decisions.1 In the pooled safety population of patients treated with BESREMi, the most common adverse reactions (incidence >40%) were influenza-like illness, arthralgia, fatigue, pruritis, nasopharyngitis, and musculoskeletal pain. Serious adverse reactions (incidence > 4%) were urinary tract infection, transient ischemic attack and depression.1

“We are incredibly proud to deliver on our goal of bringing treatments like BESREMi to the polycythemia vera community where there is clear unmet need for more effective, tolerable and durable treatments to preserve patients’ health and well-being,” said Ko-Chung Lin, Ph.D., Co-Founder and Chief Executive Officer for PharmaEssentia and inventor of ropeginterferon alfa-2b-njft. “As we begin working closely with the community to integrate this important treatment into clinical practice, we also continue to expand our scientific efforts to unlock the full potential of our pioneering molecule.”

The FDA just approved a new ORAL therapy, Scemblix (asciminib) from Novartis, for patients with Philadelphia chromosome-positive chronic myeloid leukemia previously treated with two or more tyrosine kinase inhibitors (TKIs). Studies show that around 55% of CML patients are intolerant to TKIs and 70% receiving TKIs as a second-line treatment fail to achieve a significant response. Patients who acquire T314I mutations also tend to be resistant to existing TKI therapies. The drug also received full approval for adult patients with Ph+ CML in CP with the T315I mutation.

Chronic myeloid leukemia (CML) is the most common myeloproliferative disorder accounting for ~20% of all leukemia cases. Its annual incidence has been estimated at between 1 and 1.5 cases per 100,000 and its prevalence at around 1 in 17,000. The Philadelphia chromosome is seen in more than 90% of patients with CML.

Pricing for Scemblix was not released. Channel access was not announced. However, given the small patient base for its indication it would be expected that Scemblix will launch via limited distribution.

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FDA approves Scemblix (asciminib) for Philadelphia chromosome-positive chronic myeloid leukemia

On October 29, 2021, the Food and Drug Administration granted accelerated approval to asciminib (Scemblix, Novartis AG) for patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs), and approved asciminib for adult patients with Ph+ CML in CP with the T315I mutation.

ASCEMBL (NCT03106779), a multi-center, randomized, active-controlled, open-label clinical trial, is evaluating asciminib in patients with Ph+ CML in CP, previously treated with two or more TKIs. A total of 233 patients were randomized (2:1) and stratified according to major cytogenetic response (MCyR) status to receive either asciminib 40 mg twice daily or bosutinib 500 mg once daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred. The main efficacy outcome measure was major molecular response (MMR) at 24 weeks. The MMR rate was 25% (95% CI: 19, 33) in patients treated with asciminib compared with 13% (95% CI: 6.5, 23; p=0.029) in those receiving bosutinib. With a median duration of follow-up of 20 months, the median duration of MMR has not yet been reached.

CABL001X2101 (NCT02081378), a multi-center, open-label clinical trial, is evaluating asciminib in patients with Ph+ CML in CP with the T315I mutation. Efficacy was based on 45 patients with the T315I mutation who received asciminib 200 mg twice daily. Patients continued treatment until unacceptable toxicity or treatment failure occurred. The main efficacy outcome measure was MMR. MMR was achieved by 24 weeks in 42% (19/45, 95% CI: 28% to 58%) of the patients. MMR was achieved by 96 weeks in 49% (22/45, 95% CI: 34% to 64%) of the patients. The median duration of treatment was 108 weeks (range, 2 to 215 weeks).

The most common adverse reactions (≥20%) are upper respiratory tract infections, musculoskeletal pain, fatigue, nausea, rash, and diarrhea. The most common laboratory abnormalities are decreased platelet counts, increased triglycerides, decreased neutrophil counts and hemoglobin, and increased creatine kinase, alanine aminotransferase, lipase, and amylase.

The recommended asciminib dose in patients with Ph+ CML in CP, previously treated with two or more TKIs, is 80 mg taken orally once daily at approximately the same time each day or 40 mg twice daily at approximately 12-hour intervals. The recommended asciminib dose in patients with Ph+ CML in CP with the T315I mutation is 200 mg taken orally twice daily at approximately 12-hour intervals.

This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. The FDA approved this application 4 months ahead of the FDA goal date.

This application was granted priority review, breakthrough designations, fast track designation, and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

We missed one…….

At the end of August the FDA approved a new therapy, Skytrofa from Ascendis Pharma (lonapegsomatropin-tcgd), indicated for pediatric patients that have short stature due to inadequate secretion of endogenous growth hormone. Skytrofa is the first weekly subcutaneous injectable growth hormone for children with growth hormone deficiency (GHD).

According to the American Academy of Pediatrics, growth hormone deficiency among humans is a rare condition and affects less than one in 3,000. In 2020 there were 74 million kids under the age of 18 in the US. So, we can estimate that there are as many as 25,000 children eligible for hGH.

Skytrofa joins a growing number (pun intended) of competing growth hormone products.
– Accretropin
– Humatrope
– Norditropin
– Norditropin
– Nutropin
– Nutropin AQ
– Nutropin Depot
– Omnitrope
– Saizen
– Serostim
– Skytrofa
– Tev-Tropin
– Zomacton
– Zorbtive

Analysts indicate that the hGH market globally surged in 2019-2020 and is expected to realize a robust 5% compound annual growth rate for the foreseeable future.

Skytrofa is dosed based on weight. It is supplied in nine quantities from 3mg through 13.3mg in prefilled cartridges. Most noteworthy is that this therapy is also supplied with an electric auto-injector (the instructions for use resemble something from IKEA). Each cartridge includes a chamber for the dry powder and a sterile water chamber for mixing with the powder….. inside the electric injector. Safety instructions state not to use near a microwave oven…. now that is something you don’t see in prescribing information every day. The electric injector is replaced after every six injections.

Skytrofa is supplied in a 4-dose carton for once weekly administration. A carton of Skytrofa with a GoodRx discount costs $2,500 – $2,700 depending on pharmacy. Finally a new therapy that is not in limited distribution.

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FDA Approves Weekly Therapy for Pediatric Patients with Growth Hormone Deficiency

FDA has approved Skytrofa (lonapegsomatropin-tcgd) injection to treat pediatric patients age one year and older who weigh at least 11.5 kg (25.4 pounds) and have short stature due to inadequate secretion of endogenous growth hormone. Skytrofa is a human growth hormone (hGH) approved for pediatric patients to take by under-the-skin injection weekly. Other available FDA-approved hGH formulations for pediatric patients with growth hormone deficiency must be administered daily.

Growth hormone deficiency is a disorder characterized by inadequate growth hormone production from the anterior pituitary gland, a small gland located at the base of the brain that produces several hormones. Children with this disorder can receive growth hormone to stimulate growth.

Skytrofa was studied in a 52-week trial that enrolled 161 pre-pubescent research participants (average age was 8.5 years) with growth hormone deficiency who had received no previous growth treatment. Participants were randomly assigned to receive either weekly injection of Skytrofa or daily injection of somatropin, an FDA-approved human growth hormone. Efficacy was determined by the increase in growth rate after 52 weeks of treatment. Weekly Skytrofa treatment for 52 weeks resulted in a growth rate increase of 11.2 cm (4.4 inches) per year and was not inferior to daily somatropin treatment.

The most common side effects of Skytrofa include viral infection, pyrexia (fever), cough, nausea and vomiting, hemorrhage (blood loss), abdominal (stomach) pain, arthralgia (joint pain), arthritis, and diarrhea. Patients with acute critical illness, allergies to somatropin or any Skytrofa excipients, active malignancy, certain types of diabetic retinopathy (eye-related diabetes complications), and Prader-Willi syndrome with other risk factors should not take Skytrofa. Children with closed epiphyses (end part of a long bone) should also not take the drug.

Patients taking Skytrofa are also at increased risk of neoplasms (abnormal tissue growth), intracranial hypertension (buildup of pressure around the brain), fluid retention, hypoadrenalism (underactive adrenal gland), hypothyroidism (underactive thyroid), slipped capital femoral epiphysis (a pediatric hip condition), progression of preexisting scoliosis, and pancreatitis (inflammation of the pancreas).

Skytrofa may interact with glucocorticoid (a type of steroid) treatment, oral estrogen, insulin, and other antihyperglycemic (blood sugar-reducing) agents.

Most of us that work in the specialty pharmacy segment are very familiar with the concept of a HUB. At its rudimentary level a HUB acts as a clearinghouse for a drug to expedite getting the therapy from the prescriber to the patient as efficiently as possible. As is often the case, the therapy is in limited distribution, so the HUB directs traffic to put the prescription on a track to a designated pharmacy. That’s about where the knowledge level starts to fall off for many.

The article below is a good read for new SP staff to get a thorough introduction to the HUB concept. But, it is also a good read for more experienced staff to fill in any blanks so they can give a fulsome explanation of what a HUB does and the benefits and complexities associated with the model.

A couple points that the article did not include—–
– First, many HUBs include multiple participating specialty pharmacies. An underlying reason is that not all specialty pharmacies have payer contracts for reimbursement. By stitching together a network that expands payer reach fewer roadblocks to patient authorization will be encountered.
– Secondly, the importance of data is understated. Manufacturers have increasingly relied on specialty pharmacies to report on ever more granular details including patient status, reasons for termination of therapy, occurrence of ER admissions, patient health progress, etc., etc. These additional data items are usually tailored to each specific therapy. Such services also provide an important revenue source for the specialty pharmacy.

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The Value of a Hub in a Limited Distribution Specialty Pharmacy Network

Although specialty pharmacies may be able to offer some of the services that a hub provider does, a hub can standardize patient and provider support across the network.

“What is a hub?”
“What does a hub do?”
“Why is a hub needed?”
“Why would a manufacturer select a hub as part of their network?”

I find myself answering these questions often. For a non-industry native, I find it hard to provide a succinct answer. Fundamentally, a hub provider serves as an extension to the drug manufacturer and administers their branded support programs.

In many instances, a hub proves to be extremely valuable in a network because it can provide unique program services. These services aim to enhance coordination of care, patient access, financial support, and patient and prescriber engagement. Services include, but are not limited to:
– case management
– reimbursement and co-pay support
– specialty pharmacy triage
– network coordination and reconciliation of referrals
– field team support
– nurse navigator and psychosocial support
– free drug qualification and non-commercial pharmacy dispensing
– patient clinical support
– health care provider education
– execution of Risk Evaluation and Mitigation Strategy (REMS) program
– data reporting, analytics, and digital solutions

To get a better understanding of these services and why a hub is poised to provide these services, an understanding of the limited distribution network is warranted.

Understanding the Limited Distribution Network
Beginning at a few years prior to the anticipated Prescription Drug User Fee Act (PDUFA) date and launch of a product, a biopharmaceutical company must define its distribution strategy. This includes designing the network of specialty pharmacies and whether to include a hub service provider, data aggregator, and other vendors.

The number of specialty pharmacies to include in the network heavily depends on the size of the patient population anticipated to be treated with the therapy being commercialized. The larger the patient population, the more pharmacies are likely included in the network.

Depending on the disease state, product considerations and the anticipated size of the patient population, certain specialty pharmacies are considered. For example, if a biopharmaceutical manufacturer is launching an oncology product, they should consider oncology-focused specialty pharmacies.

Similarly, if a product is ultra-rare, then a rare disease-focused specialty pharmacy is the obvious choice to pursue.

Payer and reimbursement factors also play a role in the number and type of specialty pharmacies to include in the network. A biopharmaceutical company must ensure that the network they select enjoys broad coverage of the major payers to guarantee product reimbursement. This can be accomplished by selecting all pharmacy benefit manager (PBM)-owned pharmacies.

Alternatively, a manufacturer can select all independently owned pharmacies without providing access to the product to the PBM-owned pharmacies, which prevents payers from mandating product be filled at their pharmacies.

Once the commercial specialty pharmacy strategy is understood, a decision is made on whether to include a hub service provider in the network. If the patient population is small and the manufacturer decides on an exclusive model in which a single specialty pharmacy has access to the product, then including a hub may not be necessary.

However, as the number of pharmacies grow, positioning a hub to “quarterback” the network becomes the right choice to make.

“So why do I need a hub if specialty pharmacies can do it?”

The Value a Hub Service Provider
A hub can play an essential role in coordinating the specialty pharmacy limited distribution network. Although specialty pharmacies may be able to offer some of the services that a hub provider does, a hub can standardize patient and provider support across the network and coordinate referrals to ensure patients end up at their most appropriate destination.

Referral Reconciliation: Depending on whether the hub model is mandatory or not, referrals can end up at multiple places within the network. The right hub strategy uses a proactive approach to reconcile referrals across the network and ensure no patients are left behind. If referrals are in a stalemate or are being serviced by multiple pharmacies simultaneously, causing unnecessary payer blocks, the hub can step in to assist. This ensures only one pharmacy is moving the patient to therapy or preventing a lapse in therapy.

Sophisticated Network Triage: Sending hub referrals to the appropriate pharmacy is an important role only a hub can play. If the right hub strategy is chosen, it can set up automated triage rules based on payer mandates, physician preference, round robin, and other rules to guarantee referrals make it to the pharmacy that has the highest likelihood of getting a paid claim. If done right, a hub can have a tremendously positive effect on time to therapy by minimizing network transfers.

Enhanced Data Visibility: A hub plays an important role in increasing Health Insurance Portability and Accountability Act (HIPAA) authorization and consent rates into additional programs. Referrals can come into the hub with patient signatures. If that is not the case, the hub can follow up during a welcome call to obtain consent, ideally digitally via e-consent. With increased HIPAA authorization rates comes increased data visibility to the manufacturer. Additionally, if the right hub strategy is chosen, it can set up data agreements across the network to enhance data visibility, allowing it to play an active role in referral reconciliation.

Customizability: Hub providers have a core set of services they offer, but also have the ability to highly customize when necessary. This involves customizing the process flow based on patient and provider needs, the patient engagement journey, and data reporting. The right hub strategy is nimble, able to make process changes on the fly, and captures any data element required for reporting.

Other Important Services a Hub Provides
Case Management and Field Team Support: A hub can employ dedicated case managers that serve as a main point of contact to patients and prescribers. They can assist patients in navigating their journey to treatment and beyond. They can serve as a patient advocate. They can also assist health care providers with prescribing the medication and send field-based team members to properly support prescribers.

Reimbursement and Co-pay Support: Depending on the model, the hub can assist with drug reimbursement and co-pay support. In a mandatory hub model, the hub performs detailed benefits investigation, supports prescribers through prior authorizations and appeals, and triages clean claims to pharmacies for dispensing. After launch, a hub can quickly learn payer requirements, stay up to date with formulary updates, and work with the manufacturer’s market access team to ensure optimization of payer coverage. For commercially insured patients, the hub can enroll them in a co-pay program and communicate the co-pay identification to the pharmacy to use at adjudication, minimizing the patient’s out-of-pocket burden.

Nurse Navigator and Psychosocial Support: A hub can enhance patient engagement through nursing and psychosocial support. Nurse navigators can serve as a patient resource through disease state education. They can conduct needs assessments to understand the patient’s knowledge and familiarity with their diagnosis. They can assess the patient’s support system and guide them through their journey. They set the expectation for next steps regarding coverage determination and specialty pharmacy triage. Based on findings from needs assessments, nurse navigators schedule follow ups to discuss appropriate topics that will be beneficial to the patient.

Free Drug Qualification and Non-Commercial Pharmacy Dispensing: A hub can administer free drug programs, such as patient assistance programs, bridge, quick start, dose exchange, voucher, and other forms of “free” drug. This includes qualifying patients based on business rules and triage to a non-commercial pharmacy for dispensing. Ideally, the hub owns a non-commercial pharmacy licensed in 50 states. Having an in-house non-commercial pharmacy prevents roadblocks associated with an outsourced pharmacy that may not be able to accommodate specific program nuances.

Patient Clinical Support: If the hub leverages nurse navigators for disease and psychosocial support, the non-commercial pharmacy can leverage pharmacist clinical support for patients on free drug. Clinical pharmacists can educate the patient about the medication, side effect profile and potential drug-drug interactions. They can set the expectation of the benefit of taking the medication, what to do if doses are missed, how to store the medication and address any questions. If the medication requires a titration, weight-based dosing or has special dosing considerations, the pharmacy can support patients and prescribers through proper administration and dose optimization.

Health Care Provider Education: This includes educating prescribers on sending complete enrollments, guiding them through the reimbursement process and supporting them with medication prescribing and dose adjustments. The hub can provide a dedicated, single point-of-contact to prescribers for protocol support.

REMS Program Execution: If a REMS program is required by the FDA, the hub can customize its process flow to fulfill REMS requirements. This can include medication guide requirements, guiding prescribers to enroll in a program and provide the necessary attentions, enrolling patients and counseling them on potential risks, verifying these enrollments prior to shipments, adverse events reporting, and so forth.

Data Reporting, Analytics, and Digital Solutions: In addition to the services discussed above, hubs communicate activities to the manufacturer through reporting and analytics. Standard reports include status, dispense, and inventory files. Hubs have experience working with data aggregators, have the ability provide custom reports, and have the capability to provide real time insights. Other digital solutions include texting and emailing capabilities, e-consent, electronic prescribing, etc.

Selecting the “Right Hub”
Similar to selecting specialty pharmacies, it is preferred that the hub is focused in the treatment area, such as rare disease for an orphan drug or oncology-focused for a cancer medication. In addition to that, the right hub is dedicated, proactive, attentive to detail, and plays an active end-to-end role in the network.

The right hub is nimble, quickly adaptable, and delivers on promises. Similarly, the right hub has an in-house non-commercial pharmacy that provides a consistent experience with the commercial specialty pharmacies in the network and integrates seamlessly with the patient service provider.

In conclusion, the right hub service provider acts as an internal, external hub to the manufacturer, executing their brand support program flawlessly and setting up the limited distribution network to succeed.

Rami Chammas, PharmD, MPBA
Pharmacy Times

Announcements for newly approved specialty drugs often state that the product will be available through specialty pharmacy in limited distribution. However, the press releases rarely specify the specialty pharmacy(ies) selected as the designated partner(s).

Here are a few LD deals that have been recently publicly confirmed subsequent to the approvals.

Orsini Specialty Pharmacy
Sanofi has selected Orsini as a limited distribution partner for Nexviazyme (avalglucosidase alfa-ngpt). Nexviazyme, an enzyme replacement therapy (ERT), is used for treating patients one year of age and older with late-onset Pompe disease (lysosomal acid alpha-glucosidase [GAA] deficiency).

AllianceRx Walgreens Prime.
Arcalyst (rilonacept) is the first and only FDA-approved product for the treatment of recurrent pericarditis and reduction in risk of recurrence. Pericarditis is a painful and debilitating autoinflammatory cardiovascular disease associated with swelling of the sacklike membrane surrounding the heart. Arcalyst is also approved by the FDA for the treatment of Cryopyrin-Associated Periodic Syndromes (CAPS), a group of rare hereditary autoinflammatory disorders, including Familial Cold Autoinflammatory Syndrome and Muckle-Wells Syndrome, and for the maintenance of remission of Deficiency of Interleukin-1 Receptor Antagonist (DIRA), an autoinflammatory disease affecting fewer than 50 people worldwide. Kiniksa Pharmaceuticals manufactures Arcalyst, which is also a registered trademark of Regeneron Pharmaceuticals, Inc.

Gavreto (pralsetinib) is a once-daily oral prescription medicine used to treat certain cancers caused by abnormal RET-positive (rearranged during transfection) genes in non-small-cell lung cancer that has spread (metastatic) or advanced thyroid cancer that may have spread. Blueprint Medicines manufactures Gavreto.

Maxor Specialty Pharmacy
Elixir has selected Maxor as its exclusive Cystic Fibrosis (CF) provider in its specialty pharmacy network. Maxor Specialty Pharmacy will provide Elixir CF patients with case management, education, such as how to clean and maintain their equipment, and fulfill their prescriptions. Maxor is one of four pharmacies in the United States with access to all CF drugs, including Trikafta.