So, can you easily explain the differences between a chemically synthesized drug and a biologic?
You might be surprised how difficult that has become.

The article below should be thought provoking for those in the specialty pharmacy industry as it goes to the core of what exactly SPs actually sell….. chemically synthesized drugs and biologics. But…. if you were asked to list which column your drugs should be listed you would likely be stumped.

Here’s why….. the Consolidated Appropriations Act of 2020 included new guidance on how drugs can be classified. Specifically, the change states that the purpose of the amendment is to allow for the possibility that a manufacturer may chemically synthesize a biologic product. Huh??

Here’s an example…. Vondys 53, a biologic analog made through synthetic chemistry – not by any biologic process – is considered a biologic. The author of the (somewhat ‘tongue in cheek) article below polled pharma colleagues for their opinion as to whether similar drugs – are or aren’t biologic drugs.
The results:
41% agreed that these new drugs were biologics, 39% disagreed, 20% responded “Confused”
….. so am I.

Non-pharmacists may be a bit intimated by the technical references in the article…. just skip over them as that’s not the point of this Alert. The real purpose is to alert those working in the specialty pharmacy industry that today’s crop of new biologics ‘ain’t your grandfather’s biologics’. If you are going to be selling both chemically synthesized drugs and biologics you should have, at a minimum, a basic understanding of these developments.

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What is a Biologic Drug Anyway?

Or, How I Learned to Stop Worrying and Love My Own Definition

January 19, 2020 — Recently I posted on “biologic drugs” which were approved in 2019. All was well in my little scientific universe, until I received this in an email:

“You recently reported on “14 novel biologic drugs,” referring to ‘novel’ biopharmaceuticals approved through CDER. But, … You also include several synthetic drugs, which are clearly not biopharmaceutical/biologics.”

Wait, what? Synthetic drugs are clearly not biopharmaceutical/biologics? Sure, the siRNA drug, Givlaari, and the antisense oligonucleotide, Vyondis 53, are both technically made by chemical synthesis. But, not considering these RNA-based drugs “biologic drugs” just felt… wrong.

It got me thinking – what is the definition of a biologic drug, anyway? I immediately started my research the way any good, card-carrying scientist does — I punched it into the Google:

GOOGLE: A biopharmaceutical, also known as a biologic medical product, or biologic, is any pharmaceutical drug product manufactured in, extracted from, or semisynthesized from biological sources. [source] Wikipedia

Though Wikipedia delivers good answers to probably 90% of my questions, I knew this definition was incomplete – nobody considers natural products like penicillin “biologic drugs.” Not wanting to spend the rest of my Sunday night reading FDA guidance documents, I did instead what any good millennial does – I asked social media.

As one comment pointed out, the term “biologic” itself is anachronistic, coming from a time when chemistry and biology were considered distinct (i.e. before chemists started getting upset about Nobel Prizes in Chemistry going to “biologists”). The Biologics Control Act, which first gave the US government control over the processes to make biological products, was passed in 1902 – long before it was clearly established that proteins are polymers of amino acids and that genetic information is stored chemically in nucleobases.

Digging Deeper
Based on the lack of strong consensus, I decided this was a topic worth diving further into.

Readers likely remember that “biologic” became a charged term in the 2000’s, due to expensive biologic products like filgrastim and epoetin alfa, approved under Biologic License Applications (BLAs) rather than New Drug Applications (NDAs). Since the abbreviated generic drug approval process (ANDA) only applied to originals filed under NDAs, there was no way to create a “generic” biological product without repeating expensive and lengthy clinical trials. This loophole led to the creation of the abbreviated follow-on biologicals approval pathway (aBLA) through the 2009 Biologics Price Competition and Innovation Act (BPCI).

So how are the adjectives, “biologic” or “biological,” legally defined in the US Code of Laws after BPCI in 2009? Turns out, they’re not. The term “biological product,” is legally defined only with examples, not properties:

“The term “biological product” means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.”
42 U.S. Code § 262. Regulation of biological products.

With no basis in the text for determining what an “analogous product” is, no definition of what exactly makes a product “biologic” or “biological,” and with, of all things, arsphenamine (or any other trivalent organic arsenic compound) being the only exemplified exception, no wonder everyone is confused. The FDA and the industry spend an enormous amount of resources deciding new registrants on a case-by-case basis, which was part of the justification for a recent change in the definition.

A Legal Update on Synthetic Processes
It gets better. The Further Consolidated Appropriations Act, 2020, signed into law in December 2019, amended this definition by removing the phrase “except any chemically synthesized polypeptide”:

“The term “biological product” means a virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product, protein (deleted: except any chemically synthesized polypeptide), or analogous product, or arsphenamine or derivative of arsphenamine (or any other trivalent organic arsenic compound), applicable to the prevention, treatment, or cure of a disease or condition of human beings.”

New legal definition of “biological product” after the Further Consolidated Appropriations Act.
The recent FDA press release on the change states that the purpose of the amendment is to allow for the possibility that a manufacturer may chemically synthesize a biologic product. Under the old definition, if an original biologic product was licensed under a BLA, a new chemically synthesized biologic follow-on could not be licensed through an abbreviated aBLA pathway, since it was made by a synthetic process, but also could not be licensed through an ANDA, since the original was not filed under an NDA.

In the end, what this demonstrates is that there are at least two simultaneous uses of the term “biologic” in the industry – an arbitrary regulatory definition to decide what drugs are licensed under BLAs vs. NDAs, and a scientific colloquialism which most of us use on a day-to-day basis. Neither definition is clear and unambiguous, and no single criterion (e.g. chemical process) universally captures all cases.

Biolognas, Anybody?
Having both uses at the same time is confusing enough to make you want to give “synthetic biologics” a different name without “biologic” in it. But what would we call them? Biologishes? Biolognas? I guess I have a year to think about it before 2020’s Biologic Drug Approvals post.

But back to my original question– since oligonucleotide drugs are all filed under NDAs, they’re regulated more like most small molecules than most biologics. But just because they’re filed under NDAs, doesn’t mean we can’t still call them biologics (e.g. insulins are all filed under NDAs). Anyway, all this makes me very glad that we have a lot of brilliant professionals working in our very important Regulatory Affairs departments, though I’m glad it doesn’t include me!

We dog eared the article below some time ago but never got around to including it in a weekly Anton Rx Report. It is insightful making the point that regulatory policies are creating legal log jams slowing the approval of new, competing therapies.

Specialty pharmacies historically benefited from new brand products coming to market. In most cases they were 5-10% or more costly than the last generation product…. so revenues benefited. These days, however, most of the new approvals are uber costly orphan drugs and are launched through limited distribution. As such, the majority of specialty pharmacies don’t enjoy any measurable benefit.

To keep the revenue pipeline robust, specialty pharmacies would actually benefit from access to new generic and biosimilar products. Hey, some revenue is better than NO revenue. So, when older brands lock out new. lower priced products the market can stagnate. And, those patients facing hefty out-of-pocket costs for the new wonder drug might be happy to access a last generation product or biosimilar that might now be available on a lower cost benefit tier.

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New Biologics Are Skewing Exclusivity Periods Longer, Study Says

The rise of biologics as a class of prescription spending is fueling a trend toward longer exclusivity periods, which ultimately makes access more remote, authors of a new study said.

More new drugs tend to be biologics, approximately 1 in 4, which is a concern because biologics tend to command higher prices and enjoy longer market exclusivity, thereby fending off competitors such as biosimilars that would bring prices down and improve access, authors of a new study wrote.

They studied exclusivity periods for a range of generic and biologic products to understand the changes that are occurring and spot important trends.

“High drug prices charged during exclusivity periods allow drug manufacturers to recoup returns on earlier investment in drug development. However, unnecessarily lengthy exclusivity periods contribute to excess health care spending, and it is not clear whether the current system is financially incentivizing clinically important innovations,” investigators wrote.

Current marketing exclusivity periods for drugs range from 13 to 17 years, although biologics tend to have longer exclusivity, they found. “Policymakers should consider options to encourage timely competition, particularly among biologic drugs.”

The authors used claims data to estimate market exclusivity for 264 small molecule and 4 biologic drugs that faced new generic or biosimilar competition from 2012 to 2018. The exclusivity periods for biologics averaged 21.5 years versus 14.4 years for small molecule drugs (P = .02).

Investigators also found that drugs with lower annual revenues tended to have longer exclusivity periods:
< $75 million = 16.6 years
≥ $500 million = 14.2 years
(P = .006)

Investigators found that versions of existing drugs that had been modified (eg, administration route, therapeutic area) or gained approval via use of expedited approval pathways had shorter exclusivities than new drugs (9.9 vs 14.5 years; P < .01).

Periods of exclusivity make it possible for manufacturers to charge high prices for their innovator drugs, which is partly why brand-name products account for 80% of US prescription drug spending. Once competitor products enter the market, prices may drop substantially, leading to lower-out-of-pocket spending, improved medication adherence, and patient outcomes, authors said.

Therefore, market exclusivity periods are an important factor to consider in the patient-access equation, they said.

The study drew upon records from 17 million commercial and Medicare Advantage patients in 50 states, as well as FDA lists of generic and biosimilar approvals from 2012 to 2018. The study encompassed 109 new products and 159 modified products.

Modified drugs approved under an expedited FDA pathway had longer exclusivity than regular pathway drugs (15.1 vs 9.7 years; P = .01).

Therapeutic area and route of administration also correlated with exclusivity length, with longer periods for new products in the hematology/oncology (14.3 years), infectious disease (16.1), and dermatology (17.0) arenas, and longer periods also for topical (27.6), inhaled or intranasal (17.1 [modified drugs only]) or injected products (15.4).

Authors of the study said they did not find evidence that exclusivity periods lengthened for new small molecule drugs between 2012 and 2018. But longer exclusivity periods were noted “among the first 4 biologic drugs to face biosimilar competition, which is notable because biologics account for a rising proportion of new drug approvals.”

The lack of automatic substitution of biosimilars at the pharmacy counter has the potential to limit competition for innovator drugs, but biosimilars can still make an important difference via their lower prices, the authors said. “Since biosimilar competition can still lead to modestly lower prices even without automatic substitution, timely biosimilar competition is still important for improving patient access to lower-cost treatments and limiting unnecessary spending on these expensive products.”

Investigators found that a generic pathway created via the Hatch-Waxman Act appears to have succeeded in incentivizing earlier generic competition. Hatch-Waxman was designed to encourage generic competition by allowing 180 days of exclusivity to the first generic product to gain tentative FDA approval and go to market against an established brand-name drug. Shorter exclusivity periods resulted from this policy, but for almost 50% of new drugs, the first generics did not qualify for the 180-day exclusivity period, investigators found.

They said it remains to be seen whether the FDA’s 2017 Drug Competition Action Plan is able to encourage generic competition and increase generic approvals. “It will be critical to examine whether exclusivity length eventually shortens,” they said.

A recent study emphasized the importance of improving access to biosimilars as a way to generate better outcomes and lower costs for medicine.
Tony Hagen, AJMC

Patients on complex specialty therapies always have lots of questions. Lately they have been asking lots of questions about the Covid-19 vaccines and whether they are safe for given that they many are immune compromised. The good news… as detailed below, currently approved vaccines are safe for MS patients. But…..

We recently sent a report on this question pertaining to patients on inflammatory therapies. It included detail on the timing of vaccine administration and temporary pausing the specialty therapy. Today we are spotlighting MS patients. Their Disease Modifying Therapies (DMTs) can diminish immune response to the vaccines since they are designed to suppress the body’s immune system.

So, how long after the DMT is paused is it advised to receive vaccine and how long after the vaccine is administered is it advised before restarting or starting each DMT? See the list of drugs below.
Yes, there will be a quiz!

A specialty pharmacy usually has detailed clinical protocols for all its therapies. The vaccines present a great opportunity for targeted protocols…. by therapy. Manufacturers should be able to provide this information, so you don’t need to do all the heavy lifting.

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National MS Society Offers Guidelines for Timing of COVID-19 Vaccines

March 29, 2021 — Vaccines for COVID-19 are safe and strongly recommended for all patients with multiple sclerosis (MS), according to new guidance from the National MS Society.

The guidance urges all MS patients to get vaccinated as soon as possible. Those in high-risk groups whether due to having progressive MS or any other reason “are especially encouraged to get vaccinated as soon as it becomes available,” the guidance states.

“A question that does come up, though, is whether to consider timing the vaccination relative to some of the disease-modifying therapies (DMTs) to maximize the immune response to the vaccine,” Dr. Bar-Or said. The guidance notes that some DMTs might diminish patients’ immune response to the vaccines, precisely because they are designed to tamp down the body’s immune system.

Specialists should consider how long after the DMT they should start vaccine and how long after the vaccine they might wait prior to restarting or starting DMT, Dr. Bar-Or said.

For some DMTs, it is enough to wait two weeks, for others it would be probably better to wait four weeks between completed vaccines and (re)starting DMT, he said, adding, “This may warrant a case-by-case discussion between the person living with MS and their provider, since settings and circumstances can differ.”

For example, Dr. Bar-Or said, a patient who is prescribed ocrelizumab for active relapsing MS, who is younger, not disabled and without comorbidities, could get the COVID-19 vaccine when it is offered, or plan to complete the vaccination several weeks prior to the next regularly scheduled ocrelizumab infusion.

“In contrast,” he said, “a patient prescribed ocrelizumab for primary progressive MS—who may also be older, more disabled and have one or more co-morbidities, and therefore at higher risk of severe COVID-19,—is unlikely to lose much ground if his ocrelizumab infusion is delayed by up to two or three months, potentially allowing for more robust vaccine response. That’s why it’s important for patients to discuss any timing adjustments with their neurologist.”

Guidance for Specific MS Drugs
No adjustment in timing is necessary, the guidance states, for MS patients taking beta interferons, any glatiramer acetate, teriflunomide, monomethyl fumarate generic dimethyl fumarate, diroximel fumarate, or natalizumab.

For patients whose MS is stable, neurologists and patients can consider the following adjustments in the administration of the DMT to maximize the vaccine’s effectiveness. Such scheduling is not always possible, however, and the guidance emphasizes that getting the vaccine when it becomes available may be more important than coordinating timing of the vaccine with the DMT dose.

• Sphingosine 1 phosphate receptor modulators: If a patient is about to start taking one of these medicines for the first time, they and their physician can consider waiting two to four weeks or more after getting fully vaccinated. If they are already on these therapies, they should continue taking them as prescribed and get vaccinated as soon as the vaccine is available to them.
• Alemtuzumab: If a patient is about to start alemtuzumab for the first time, they and their physician should consider waiting four weeks or more after being fully vaccinated. If they are already taking alemtuzumab, they should consider getting vaccinated 24 weeks or more after the last alemtuzumab dose. If they are due for their next treatment course, when possible, they should resume the therapy four weeks or more after getting fully vaccinated.
• Oral cladribine: If a patient is about to start cladribine, they and their physician should discuss waiting two to four weeks after getting fully vaccinated. If they are already taking cladribine, the currently available limited data does not suggest that timing of the vaccine in relation to the dosing is likely to make a significant difference in vaccine response. If they are due for their next treatment course, when possible, they should resume cladribine two to four weeks after getting fully vaccinated.
• Anti-CD20 monoclonal infusions (ocrelizumab, rituximab, and biosimilars): Patients who are about to start infusions of these therapies should discuss with their neurologist if it would be safe to wait two to four weeks or more after getting fully vaccinated. If they are already taking ocrelizumab or rituximab, they can consider getting vaccinated 12 weeks or more after the last DMT dose. When possible, ocrelizumab or rituximab should be resumed four weeks or more after getting fully vaccinated.
• Ofatumumab: Patients about to start ofatumumab for the first time should consider, in consultation with their physician, waiting two to four weeks or more after getting fully vaccinated. If they are already taking ofatumumab there is no data to currently guide timing of the vaccine in relation to their last DMT injection. When possible, the guidance recommends, patients should resume these injections two to four weeks after getting fully vaccinated.
• High-dose steroids: Patients and physicians should consider waiting at least three to five days after the last dose of steroids to begin the vaccine injection(s).

COVID-19 Vaccine Guidance for People Living With MS.

Curiouser and curiouser…….
The pharmacy management rabbit hole seems to be getting curiouser by the day. The article below details a very new and provocative tactic to pull patients off one therapy and onto another, one that has clear benefits for the PBM and questionable clinical benefits for the patient.

Like all PBMs lately, changes to drug formularies have seen drugs moved to non-preferred status or even to ‘no longer covered’ in favor of another that is now preferred. What is unique is that Express Scripts is offering a cash bonus to certain patients on specialty therapy to drop their established therapy in favor of the new, preferred drug. Sure, $500 is enough to catch a patient’s attention and perhaps grease the skids to force a change. But the article points out that there may be unexpected clinical consequences with making the switch.

Also, the program isn’t offered across therapies or even across therapeutic categories. The article below notes that the current program only targets psoriasis patients. That raises the question….. Who benefits most? We all know that rebates are behind every preferred formulary decision so the answer can be easily construed that the PBM could be the bigger winner.

This may be a trial balloon, but it is noteworthy. Will we see similar deals offered to prompt more patients to move their specialty therapy? Will PBMs that use this technique also get blow back from other members who are not offered similar incentives?

“It takes all the running you can do just to keep in the same place.”
— Lewis Carroll

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Express Scripts Dangles $500 to Persuade Patients to Switch Psoriasis Drugs

March 26, 2021 — As the first quarter of 2021 ends, patients choosing to keep using secukinumab may be offered an inducement by their pharmacy benefit manager to switch to another biologic, ixekizumab.

Is a $500 debit card from a pharmacy benefit manager (PBM) the new carrot in patient incentives in annual formulary changes?

Every year, PBMs change what’s covered and what’s not, often in specialty drug categories but also in older classes of drugs.

This year, one of the more notable switches was the removal of secukinumab from the formulary for Express Scripts, owned by Cigna. Patients are being given the option of switching to another inhibitor of interleukin (IL)-17A, ixekizumab.

Both drugs are used for psoriasis and psoriatic arthritis. Secukinumab (Cosentyx) is sold by Novartis and ixekizumab (Taltz) is sold by Eli Lilly. In some plans, secukinumab was removed entirely; in others, it was moved to a higher-priced tier.

Now, nearly 3 months into 2021, patients who choose to keep using the therapy may see communications about the offer, according to one dermatologist who shared the letter with The American Journal of Managed Care® (AJMC®).

The letter, sent this month to clinicians, advises them of patients who are still using secukinumab and offers alternatives, including older biologics, in addition to ixekizumab. Patients would receive the debit card if they fill the first prescription before August 31 and the second before December 31, with the card to follow 6 to 8 weeks after that.

The practice, known as non-medical switching, “is a very hot topic right now,” said Mark G. Lebwohl, MD, a professor of dermatology at the Icahn School of Medicine at Mount Sinai, where he is also dean of clinical therapeutics.

“A standard thing in medicine is, if you are doing very well on a treatment, why would you stop it?” said Lebwohl, who is also on the medical advisory board of the National Psoriasis Foundation (NPF).

In a statement to AJMC®, Cigna, which owns ExpressScripts, said patients were “offered several alternative medications that are equally effective and more affordable.”

“In rare occasions when a patient is not able to use the preferred option, we recommend that our clients offer an efficient review process to assist those patients in obtaining a non-formulary medication in these instances.”

Lebwohl disagreed, saying, “They say there is an appeals process, but everything they do is onerous.”

With the rise of specialty drugs, usually biologics, non-medical switching has become more of an issue. Specialty drugs make up a little more than 2% of US prescriptions, but account for half of drug spending, and that share is expected to rise.

Dermatology and rheumatology are 2 of the specialties most often affected.

“They pick on dermatology for sure, because they figure no one’s going to die,” said Lebwohl.

Indeed, a paper led by the Institute for Clinical and Economic Review (ICER) and published in the Journal of Comparative Research, referenced that idea, noting that, “Many economic-step therapy policies involve dermatologic, antihypertensive and gastrointestinal motility drugs that treat conditions for which short-term failure with the first-step drug poses extremely little risk of any significant long-term harm.”

The paper proposes a set of what is calls “ethical goals for access and fair design criteria” that could be used to spur “transparent and accountable drug coverage,” including points that should be satisfied if required switching is to take place.

However, the authors also note that their ideas will likely leave everyone unhappy.

“It will leave some patient advocates and clinician representatives feeling that too much weight has been given to the importance of managing limited health care dollars, and that too much discretion has been allowed to payers to construct policies that put patients at risk,” the authors conclude. “Conversely, many payers will feel that this paper questions unfairly their moral compass; that their commitment to evidence is discounted, while their efforts to make sure that patients are not hurt by inappropriate prescribing lie undefended from misplaced suspicions that the bottom line drives their actions.”

The NPF is having conversations with payers and PBMs about these issues, said Leah McCormick Howard, chief operating officer of the NPF. Part of that conversation is education about the systemic nature of psoriasis, she said.

“From an NPF perspective we’re always concerned about policies that require or would encourage an individual in our community who’s stable on a therapy to switch to another therapy,” she said.

Neither she nor a pharmacy professor had ever heard of an incentive set that high.

“A lot of time patients get really attached to that drug because it is working for them and it can take them 1 to 2 years to adjust to a new product,” said Nicole Henry, PharmD, assistant professor at The College of Pharmacy at The University of Arizona.

Both Henry and Howard noted that the list of exclusions by PBMs have been growing in recent years.

Lebwohl suggested that the issue has more to do with the rebate system that exists between drug companies and PBMs. Both biologics are priced similarly.

Allison Inserro
AJMC
https://www.ajmc.com/view/express-scripts-dangles-500-to-persuade-patients-to-switch-psoriasis-drugs

Specialty pharmacies won’t be dispensing Abecma (idecabtagene vicleucel), approved by the FDA last week. Abecma is an INFUSED cell-based gene therapy to treat adult patients with multiple myeloma who have not responded to, or whose disease has returned after, at least four different types of therapy. Abecma is the first cell-based gene therapy for Adult Patients with Multiple Myeloma.

As you should know by now, these treatments are personalized, made up of a patient’s own immune cells extracted and shipped to processing facility. There, the cells are genetically modified to target a particular protein that acts as a flag for the cancer. The modified cells are manipulated to create a 1-time treatment dose that is shipped back to the facility for infusion.

Celgene Corporation, a Bristol Myers Squibb company, set a price of $419,500 for Abecma. Analysts believe that Abecma will be one of the top-10 sales leaders by 2025. Top 10 by 2025.

We ask this question each time a CAR T therapy is approved…..
So why should specialty pharmacies want to know about a therapy that they can’t dispense?

Simple….. more than 500 gene-based therapies are in development. That should raise a flag for specialty pharmacies. We may start seeing even the most recent generation of SP dispensed ‘wonder drugs’ replaced by 1 dose gene therapies.

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

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

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FDA Approves First Cell-Based Gene Therapy for Adult Patients with Multiple Myeloma

March 27, 2021 — The U.S. Food and Drug Administration approved Abecma (idecabtagene vicleucel), a cell-based gene therapy to treat adult patients with multiple myeloma who have not responded to, or whose disease has returned after, at least four prior lines (different types) of therapy. Abecma is the first cell-based gene therapy approved by the FDA for the treatment of multiple myeloma.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. “While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

Multiple myeloma is an uncommon type of blood cancer in which abnormal plasma cells build up in the bone marrow and form tumors in many bones of the body. This disease keeps the bone marrow from making enough healthy blood cells, which can result in low blood counts. Myeloma can also damage the bones and the kidneys and weaken the immune system. The exact cause of multiple myeloma is unknown. According to the National Cancer Institute, myeloma accounted for approximately 1.8% (32,000) of all new cancer cases in the United States in 2020.

Abecma is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose of Abecma is a customized treatment created by using a patient’s own T-cells, which are a type of white blood cell, to help fight the myeloma. The patient’s T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing myeloma cells. Once the cells are modified, they are infused back into the patient.

The safety and efficacy of Abecma were established in a multicenter study of 127 patients with relapsed myeloma (myeloma that returns after completion of treatment) and refractory myeloma (myeloma that does not respond to treatment), who received at least three prior antimyeloma lines of therapy. About 88% of patients in the study group had received four or more prior lines of antimyeloma therapy. Overall, 72% of patients partially or completely responded to the treatment. Of those studied, 28% of patients showed complete response—or disappearance of all signs of multiple myeloma—to Abecma, and 65% of this group remained in complete response to the treatment for at least 12 months.

Treatment with Abecma has the potential to cause severe side effects. The label carries a boxed warning for, cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis/ macrophage activation syndrome (HLH/MAS), neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life-threatening. CRS and HLH/MAS are systemic responses to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and prolonged cytopenia is a drop in the number of a certain blood cell type for an extended period of time. The most common side effects of Abecma include CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first one to two weeks after treatment, but some side effects may occur later. Patients with multiple myeloma should consult with their health care professionals to determine whether Abecma is an appropriate treatment for them.

Because of the risk of CRS and neurologic toxicities, Abecma is being approved with a risk evaluation and mitigation strategy which includes elements to assure safe use. The FDA is requiring that hospitals and their associated clinics that dispense Abecma be specially certified and staff involved in the prescribing, dispensing or administering of Abecma are trained to recognize and manage CRS and nervous system toxicities and other side effects of Abecma. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop after receiving Abecma.

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

Abecma was granted Orphan Drug and Breakthrough Therapy designations by the FDA. Orphan Drug designation provides incentives to assist and encourage the development of drugs for rare diseases. 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). Breakthrough Therapy designation was granted based on sustained responses observed in patients with relapsed and refractory myeloma.

Drugs approved under expedited programs, such as Breakthrough Therapy designation, are held to the same approval standards as all other FDA approvals.

The FDA granted approval of Abecma to Celgene Corporation, a Bristol Myers Squibb company.

Last week the FDA approved a new ORAL therapy, Ponvory (ponesimod) from Janssen Pharmaceutical, to treat relapsing forms of Multiple Sclerosis.

There is no shortage of therapy options that cover the full spectrum of routes of administration….. oral – subQ – infused…. from a host of manufacturers. Ponvory will face stiff market competition now dominated by big names like Roche’s Ocrevus, Novartis’ Kesimpta and Gilenya, and Biogen’s Tecfidera.

Janssen did not disclose pricing but did say that the cost of Ponvory will be comparable to other market leader products which are now priced in the $7,000 – $10,000 per month range.

Janssen is promoting superior efficacy as the reason that prescribers and patients should turn to Ponvory. But, Ponvory will be slotted on payer formularies along side other MS therapies. Those patients paying copays for their MS treatment may see no financial benefit in making a switch. Similarly, a patient paying a coinsurance for a comparably priced therapy may see little out of pocket difference. However, it will be interesting to see if payers include Ponvory in their ‘preferred brand drug’ tier. Usually that is driven by the size of the rebate to the payer.

Janssen did not disclose whether Ponvory will launch through limited distribution. Our data indicates that virtually all leading MS therapies are currently only available through limited distribution.

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FDA approves J&J’s multiple sclerosis treatment

March 19 (Reuters) – Johnson & Johnson will launch its newly approved drug for adults with relapsing multiple sclerosis (MS) in the United States in early April 2021 at a similar price point to rival treatments, the company’s unit said on Friday.

The U.S. Food and Drug Administration on Friday approved J&J’s treatment, Ponvory, treat relapsing forms of MS, Janssen Pharmaceutical Co said.

Multiple sclerosis is a debilitating neurological condition in which the immune system eats away at the protective covering of nerves.

J&J is pushing Ponvory as a once-daily oral treatment, as opposed to Kesimpta, which is injected by patients at home, or Ocrevus that is administered as an infusion in a clinic or hospital.

The approval will be cause of concern for Biogen, as it is facing Tecfidera patent expiration and increasing competition in the MS landscape.

The FDA approval was based on data from a two-year late-stage study where Ponvory demonstrated superior efficacy in significantly reducing annual relapses by about 30% compared to Sanofi’s approved MS drug Aubagio, the company said. The drug has also outdone Aubagio at reducing fatigue among patients.

J&J acquired Ponvory as part of its $30 billion buyout of Swiss biotech company Actelion in 2017, to diversify its drug portfolio as its biggest product, Remicade for arthritis, faced cheaper competition.

Ponvory is also under review by the European Medicines Agency (EMA)

Integrated specialty pharmacy services sound so upbeat it is hard to, well, beat. The integration being promoted by health system specialty pharmacies launched in recent years use integration of the whole health record as their key differentiator. Frankly, they consciously seek to make standalone specialty pharmacies look like a shabby second choices.

The article below outlines a new program being launched jointly by McKesson Corp and Vanderbilt Health Rx Solutions with the specific purpose of helping hospitals and health systems to open their own ‘owned and operated’ specialty pharmacies. They join a growing number of organizations pushing hospitals to invest in similar deals as we’ve previously reported.

Here’s the noteworthy excerpt from the press release……
“The new service will offer customized specialty pharmacy services and growth strategies to hospitals and health systems in every phase of their maturity. VHRxS’s portfolio of robust specialty pharmacy consulting services will help health systems improve patient and provider satisfaction while creating new revenue streams by fully integrating pharmacy services into specialty clinics.

In fairness, McKesson is not the first wholesaler to help shift specialty pharmacy volume to provider owned operations….. such as assisting Oncology practices to open their own in-office pharmacies. Like other wholesalers, McKesson’s specialty pharmacy division will eventually compete with the same hospital/provider owned specialty pharmacies they help create for the same prescriptions.

McKesson Expands Integrated Pharmacy Services for Specialty Clinics

McKesson, Vanderbilt Health Rx Solutions to leverage collective expertise to advance the mission of health system specialty pharmacies.

March 16, 2021 — IRVING, Texas–(BUSINESS WIRE)–McKesson Corporation, a global healthcare company, announces a new collaboration with Vanderbilt Health Rx Solutions (VHRxS), a national leader in specialty pharmacy strategy and implementation, to offer VHRxS’s full suite of specialty pharmacy consulting services to McKesson’s health system clients. This new, specialized offering from VHRxS will complement the experience of McKesson, which has offered industry-leading pharmacy services for more than 40 years, by bringing the expertise of VHRxS, which was founded by Vanderbilt University Medical Center to advance the mission of health systems specialty pharmacies nationwide.

“By collaborating with McKesson, we can better extend our expertise as a leading health system-based specialty pharmacy provider to help our peers. We know from experience that investing in your specialty pharmacy operations boosts patient and provider satisfaction, which reaps seen and unseen benefits many times over.”

The new service will offer customized specialty pharmacy services and growth strategies to hospitals and health systems in every phase of their maturity. VHRxS’s portfolio of robust specialty pharmacy consulting services will help health systems improve patient and provider satisfaction while creating new revenue streams by fully integrating pharmacy services into specialty clinics.

Scott Miller, president of McKesson Health Systems, shares, “Our teams work closely with customers to understand their challenges and this was a clear need for health systems addressing their specialty pharmacy capabilities. Along with our existing portfolio of services and solutions, this is one more way customers can achieve more for their hospitals and patients by creating new or strengthening existing revenue streams.”

McKesson’s pharmacy leaders and the VHRxS team of experienced, hands-on advisors understand the needs and challenges of health system specialty pharmacies. The teams have deep experience working with health systems in all stages of growth, from developing and implementing initial specialty pharmacy growth strategies to optimizing existing operations to reach the next level.

Jim Hayman, president of VHRxS and Chief Pharmacy Officer at Vanderbilt Health, states, “By collaborating with McKesson, we can better extend our expertise as a leading health system-based specialty pharmacy provider to help our peers. We know from experience that investing in your specialty pharmacy operations boosts patient and provider satisfaction, which reaps seen and unseen benefits many times over.”

The VHRxS consulting services will be customized to meet the needs of each health system as they address their own unique challenges and look to create sustainable specialty pharmacy programs, including:
– Opportunity assessments
– Strategic planning and guidance
– Operating model design and implementation
– Pharmacy accreditation support
– Facility and workflow design
– Access strategies for limited distribution drugs and payer networks

Everyone in the specialty pharmacy business sits up and pays attention whenever a specialty pharmacy is acquired or announces big news. After all, good competition prompts smart companies to work harder to slog their way up the leaderboard.

Each year Drug Channels publishes its list of the Top 15 Specialty Pharmacies. (Can’t tell you how often that list is used in presentations.) We’ve seen the big box pharmacies retain their positions year after year. What has been more interesting is watching the smaller pharmacies elbow themselves onto the list. Many at the top of the list have acquired SPs at the bottom of the list. The smaller players know that and are eager to preen themselves for these suitors. Many ‘targets’ were on the list only for a year or so before getting gobbled up.

But, we have to wonder whether we’ll be seeing aspiring specialty pharmacies make the list in coming years. Just look at the companies that made this year’s list. (Click the link below for access to the article.)

The big box SPs are still there, albeit some of the names have changed, with a lion-sized market share. It is noteworthy that supermarket-owned specialty pharmacies now command the middle third of the list and half of the bottom third! But what is missing? There is not a single independent specialty pharmacy in stark comparison to the same list only a few years ago.

How will the list change in future years? Here’s our prediction.
First, assuming data can be extracted, the hospital and health system owned specialty pharmacies must start to appear. They have the potential to rise rapidly into the Top 15 club…. and might have even qualified this year. Without including these entities there will be a big hole in the analysis. Second, there has been a big uptick in the number of orphan therapies that are uber expensive. The specialty pharmacies that are winning limited (often exclusive) distribution deals for rare therapies can quickly rack up enough $$$$$s to also earn a spot on the list. Any buy-and-bill revenue from these direct-to-office therapies should also be credited to these organizations to reflect an accurate picture of the broader specialty pharmacy market.

CLICK HERE TO READ THE FULL ARTICLE

Last week the FDA approved a new ORAL Oncology therapy, Fotivda (tivozanib) from Aveo Oncology, for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common type of kidney cancer and is among the ten most common cancers in both men and women. Approximately 74,000 new cases of kidney cancer are diagnosed with about 15,000 fatalities annually. The five-year survival rate is only 13%.

Fotivda will launch with a wholesale acquisition price of $24,150 per month. This compares with the $20,760 cost of Nexavar and Cabometyx (cabozantinib) with a WAC of about $21,600. Trial patients were given an average of 12.7 cycles which translates into $306,000 annually.

We have confirmed that Fotivda will launch on March 31st through limited distribution. No detail was provided as to the selected specialty pharmacy(ies).

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AVEO Oncology Announces U.S. FDA Approval of Fotivda (tivozanib) for Relapsed or Refractory Advanced Renal Cell Carcinoma

FOTIVDA is the First Therapy Approved for Adult Patients with Relapsed or Refractory Advanced Renal Cell Carcinoma Following Two or More Prior Systemic Therapies

March 10, 2021 – BOSTON–(BUSINESS WIRE)–AVEO Oncology today announced that the U.S. Food and Drug Administration (FDA) has approved FOTIVDA® (tivozanib) for the treatment of adults with relapsed or refractory advanced renal cell carcinoma (RCC) who have received two or more prior systemic therapies. FOTIVDA is an oral, next-generation vascular endothelial growth factor (VEGF) tyrosine kinase inhibitor (TKI).

“Today’s approval of FOTIVDA provides a new tool for treating patients with kidney cancer who have relapsed or become refractory to two or more prior systemic therapies,” said Brian Rini, MD, Chief of Clinical Trials at Vanderbilt Ingram Cancer Center and principal investigator of the TIVO-3 trial. “With advances in RCC treatment, patients are living longer, increasing the need for proven, well tolerated treatment options in the relapsed or refractory setting. The TIVO-3 study is the first positive Phase 3 study in RCC patients who received two or more prior systemic therapies, and also the first Phase 3 RCC study to include a predefined population of patients who have received prior immunotherapy, the current standard of care in earlier-line treatment. With this approval, I believe FOTIVDA represents an attractive intervention, and expect it to play a meaningful role in the evolving RCC treatment landscape.”

“We believe in FOTIVDA’s potential to provide a differentiated treatment option for the growing number of individuals in the U.S. with relapsed or refractory RCC, and today marks the culmination of many years of hard work and determination of many individuals to bring this therapy to patients,” said Michael Bailey, president and chief executive officer of AVEO. “With today’s approval, AVEO begins its journey as a commercial-stage company, a noteworthy accomplishment in our industry. On behalf of the entire AVEO team, I would like to thank all the patients, their families, and caregivers whose tireless efforts made this day possible.”

“Relapsed or refractory RCC is a devastating disease for which patient outcomes can be limited due to the tradeoff between tolerability and efficacy,” said Dena Battle, president of KCCure. “The FDA approval of FOTIVDA represents an exciting, meaningful advancement by providing a new treatment option for this patient population.”

The approval of FOTIVDA is based on AVEO’s pivotal Phase 3 study, TIVO-3, comparing FOTIVDA to sorafenib in relapsed or refractory advanced RCC following two or more prior systemic therapies. The application is also supported by three additional trials in RCC and includes safety data from over 1,000 clinical trial subjects.

Patients (n=350) enrolled in the TIVO-3 study were randomized 1:1 to receive either FOTIVDA or sorafenib. The main efficacy outcome measure was progression-free survival (PFS), assessed by a blinded independent radiology review committee. Other efficacy endpoints were overall survival (OS) and objective response rate (ORR).

Median PFS was 5.6 months (95% CI: 4.8, 7.3) in the FOTIVDA arm (n=175) compared with 3.9 months (95% CI: 3.7, 5.6) for those treated with sorafenib (HR 0.73; 95% CI: 0.56, 0.95; p=0.016). Median OS was 16.4 (95% CI: 13.4, 21.9) and 19.2 months (95% CI: 14.9, 24.2), for the FOTIVDA and sorafenib arms, respectively (HR 0.97; 95% CI: 0.75, 1.24). The ORR was 18% (95% CI: 12%, 24%) for the FOTIVDA arm and 8% (95% CI: 4%, 13%) for the sorafenib arm.

The most common (≥20%) adverse reactions were fatigue, hypertension, diarrhea, decreased appetite, nausea, dysphonia, hypothyroidism, cough, and stomatitis. The most common grade 3 or 4 laboratory abnormalities (≥5%) were decreased sodium, increased lipase, and decreased phosphate.

The recommended tivozanib dose is 1.34 mg once daily with or without food for 21 days every 28 days on treatment followed by 7 days off treatment (28 day cycle) until disease progression or unacceptable toxicity.

About FOTIVDA (tivozanib)
FOTIVDA (tivozanib) is an oral, next-generation vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitor (TKI). It is a potent, selective inhibitor of VEGFRs 1, 2, and 3 with a long half-life designed to improve efficacy and tolerability. AVEO received U.S. Food and Drug Administration (FDA) approval for FOTIVDA on March 10, 2021 for the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. FOTIVDA was approved in August 2017 in the European Union and other countries in the territory of its partner EUSA Pharma (UK) Limited for the treatment of adult patients with advanced RCC. FOTIVDA has been shown to significantly reduce regulatory T-cell production in preclinical models1. FOTIVDA was discovered by Kyowa Kirin.

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

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

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

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Home Infusion Therapy Accreditation Rolls Out

• Compliance a Must Under CMS Regulations

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

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

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