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The FDA just approved a new rare, GENE therapy, Vyjuvek (beremagene geperpavec-svdt) from Krystal Biotech, indicated for the treatment of patients six months of age or older with dystrophic epidermolysis bullosa (DEB).  Vyjuvek is the first-ever redosable gene therapy and the first and only medicine approved by the FDA for the treatment of DEB, both recessive and dominant, that can be administered by a healthcare professional in either a healthcare professional setting or in the home. It is a biological suspension mixed with excipient gel for topical application.

DEB is a rare and serious disease that affects the skin and mucosal tissues caused by one or more mutations in the COL7A1 gene. Vyjuvek delivers two copies of the COL7A1 gene when applied directly to DEB wounds The COL7A1 gene is responsible for the production of functional COL7 protein that forms anchoring fibrils necessary to bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin).

The new topical stops blisters and wounds from developing on DEB patient skin. Prior to this approval there was no treatment other than simply applying bandages. Vyjuvek both heals wounds and prevents skin from re-blistering while correcting the underlying skin defect of DEB. Further, Vyjuvek doesn’t require supporting technology or specialized expertise making it accessible even to patients who live far away from specialized centers. 

Pricing for Vyjuvek was announced at a list price of $24,250 per vial, which translates to an estimated steady state cost of $631,000 per patient per year.  The label for Vyjuvek specifies that the therapy should be applied by a health care professional.  However, the company also stated that it can be administered in the home.

Administration is a bit complicated requiring atypical syringe filling steps using a syringe with a needle. However, the therapy is applied without penetrating the skin in a droplet pattern. The amount of therapy used depends on the number of wounds to be treated and their size. Assuming a patient or care giver can follow the filling process, the application of droplets on the wound not seem to require a health care professional (people with hemophilia routinely dose intravenously for example). That being said, the package insert does state that a health care professional should apply the therapy IN THE HOME as well.

Distribution details were not disclosed. As Vyjuvek is designated a rare therapy, the small number of patients and its ultra-high cost would lend towards a distribution plan via specialty pharmacy distribution.

Click Here to access the package insert

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Krystal Biotech Receives FDA Approval for the First-Ever Redosable Gene Therapy, Vyjuvek

May 19, 2023

• Dystrophic Epidermolysis Bullosa (DEB) is a serious rare genetic disease that affects the skin and mucosal tissues and is caused by one or more mutations in the COL7A1 gene, resulting in lack of production of functional type VII collagen (COL7) protein
• Vyjuvek is a topical gel that addresses the genetic cause of DEB by restoring functional copies of the COL7A1 gene to patients and is the only medicine available for patients in the US
• Vyjuvek is approved for the treatment of patients six months of age or older with either recessive or dominant DEB
• Vyjuvek is approved to be administered by a healthcare professional either in a healthcare professional setting (e.g., clinic) or a home setting.

Krystal Biotech, Inc.Pittsburgh, May 19, 2023 (GLOBE NEWSWIRE) — Krystal Biotech, Inc. (the Company) (NASDAQ: KRYS), a biotechnology company focused on developing and commercializing genetic medicines for patients with rare diseases, today announced the US Food and Drug Administration (FDA) has approved Vyjuvek (beremagene geperpavec-svdt) for the treatment of patients six months of age or older with dystrophic epidermolysis bullosa (DEB). Vyjuvek is designed to address the genetic root cause of DEB by delivering functional copies of the human COL7A1 gene to provide wound healing and sustained functional COL7 protein expression with redosing. Vyjuvek is the first-ever redosable gene therapy and the first and only medicine approved by the FDA for the treatment of DEB, both recessive and dominant, that can be administered by a healthcare professional in either a healthcare professional setting or in the home.

DEB is a rare and serious disease that affects the skin and mucosal tissues caused by one or more mutations in the COL7A1 gene. The COL7A1 gene is responsible for the production of functional COL7 protein that forms anchoring fibrils necessary to bind the dermis (inner layer of the skin) to the epidermis (outer layer of the skin). The lack of functional anchoring fibrils in DEB patients leads to extremely fragile skin that blisters and tears with minor friction or trauma. DEB patients suffer from open wounds, which lead to recurrent skin infections and fibrosis that can cause fusion of fingers and toes, and ultimately increase the risk of developing an aggressive form of skin cancer.

“This is a devastating disease,” said M. Peter Marinkovich, M.D., primary investigator of the GEM-3 trial, Director of the Blistering Disease Clinic at Stanford Health Care and Associate Professor of Dermatology at the Stanford University School of Medicine. “Until now, doctors and nurses had no way to stop blisters and wounds from developing on dystrophic EB patient skin and all we could do was to give them bandages and helplessly watch as new blisters formed. Vyjuvek topical gene therapy changes all of this. Vyjuvek both heals patient wounds and prevents skin from re-blistering because it actually corrects the underlying skin defect of dystrophic EB.”

The FDA approval of Vyjuvek is based on two clinical studies. The GEM-1/2 trial was an intra-patient, open label, single center, randomized, placebo-controlled study showing that repeat topical applications of Vyjuvek were associated with durable wound closure, full-length cutaneous COL7 expression, and anchoring fibril assembly with minimal reported adverse events. The GEM-3 trial was an intra-patient, double-blinded, multi-center, randomized, placebo-controlled study that met both its primary endpoint of complete wound healing at six months and its key secondary endpoint of complete wound healing at three months. Vyjuvek was well tolerated with no drug-related serious adverse events or discontinuations due to treatment-related events.

“Data from our GEM-1/2 trial and our GEM-3 trial, published in Nature Medicine and the New England Journal of Medicine, respectively, demonstrated the strength of both studies showing that Vyjuvek safely and effectively improved wound healing,” said Suma Krishnan, President, Research & Development, Krystal Biotech, Inc. “For so many years, all we have been able to offer DEB patients was palliative care, but now, based on the strength of the Company’s clinical trial data, there is a safe and effective FDA approved treatment.”

“Today’s landmark approval of Vyjuvek as the first redosable gene therapy ushers in a whole new paradigm to treat genetic diseases and is an important milestone for patients affected by DEB as well as their families and caregivers,” said Krish S. Krishnan, Chairman and Chief Executive Officer of Krystal Biotech, Inc. “We offer our sincere gratitude to DEB patients, caregivers, investigators, US regulators, and our employees who made this approval possible. For Krystal, this is a transformative achievement that highlights our commitment to developing and commercializing novel therapies for patients with rare diseases and demonstrates Krystal’s capability as a fully-integrated company ready to launch and bring Vyjuvek to patients as quickly as possible and deliver additional transformative medicines to patients as we advance our pipeline.”

Vyjuvek is expected to be available in the United States in the third quarter of 2023, and the Company will begin the promotion of Vyjuvek immediately. To meet the needs of patients, caregivers, and families as they start and continue their Vyjuvek treatment journey, the Company has developed Krystal Connect, a personalized support program. The program includes resources that can answer questions about Vyjuvek, verify health benefits, support treatment planning and administration and provide information about financial assistance for eligible patients. For more information, patients, caregivers and healthcare professionals can call Krystal Connect at 1-844-5-KRYSTAL.

With this approval, the FDA issued the Company a Rare Pediatric Disease Priority Review Voucher (PRV), which confers priority review to a subsequent drug application that would not otherwise qualify for priority review. The PRV program is designed to encourage the development of new drugs for the prevention or treatment of rare diseases.

“With the FDA approval of Vyjuvek, the DEB population has reached a monumental milestone in the treatment of this horrible disorder. Our hopes have now been realized for a safe and effective treatment for one of the most devastating symptoms of the disorder,” said Brett Kopelan, Executive Director of debra of America, the national organization dedicated to improving the lives of all people living with EB in the US. Mr. Kopelan added, “we thank Krystal for their dedication and commitment to bringing Vyjuvek to fruition. People living with DEB will now have a significant chance of having an improved quality of life and debra will continue to work closely with Krystal to assure patients have ready access to Vyjuvek.”

A survey just released by the Pharmaceutical Strategies Group confirmed what we already know….. that the COST of specialty medications is the tipppty toppest key concern of payers. They also updated a basket of other key measures that you will want to consider.

What is surprising in the survey is the agonizingly slow pace of adoption of value-based contracting. The survey found that just 12% of payers are now employing value-based models for pricey specialty therapies. 

Value-based contracting is arguably the fairest way to compensate for uber costly drugs that ‘may’ or may not work….. so why the lack of interest?

The reasons holding back value-based contracting are actually simple. 

It requires a mutually acceptable snd very detailed metric by which value is….. or isn’t….. determined.

It requires tracking and analysis….. and lots of it. 

And it requires patience….. lots of it…..  as it may take many months – or even years – to determine if a therapy finally delivers the results set forth in the metric….. sometimes on a patient by patient basis. 

It is also surprising that SPs haven’t been proactive in value-based contracting. 

OK, it isn’t likely that the payer and manufacturer will invite a lowly intermediary to such lofty discussions. But, that’s unfortunate as the SP can shoulder much of the heavy lifting in tracking, analyzing, measuring, and reporting progress towards the required metric. 

Isn’t that what SPs have been doing for manufacturers for years now?

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Survey: Why value-based contracting for specialty drugs remains rare

By Paige Minemyer, Fierce Healthcare

May 1, 2023 — Insurers gave a mixed review to copayment assistance programs, which offer coupons and other discounts to consumers to cover the cost of high-price drugs. 

Use of value-based contracting for specialty drugs is relatively rare, and payers cite multiple hurdles to rolling out these models, according to a new report.

The Pharmaceutical Strategies Group released its annual look at trends in benefits around specialty medications, where it surveyed more than 180 employers, insurers and labor unions. The survey found that just 12% are using value-based models for pricey specialty therapies.

Why is adoption so low? The surveyed payers said they need to see more evidence that the models are effective and also cited challenges in agreeing on and tracking outcomes. In addition, they said that resources and buy-in were lacking, making it harder to roll out value-based contracting for these therapies.

The survey also found that 14% of employers and 7% of health plans are deploying alternative funding models, while 14% and 33%, respectively, are exploring their use. However, 68% of those polled said they don’t view these models as sustainable.

Specialty pharmacy costs, mental health are top employer concerns. Here’s why

“As plans continue to seek ways to offset specialty drug costs, the market is divided as to whether alternative funding is a positive option or a detriment,” said Michael Lonergan, Pharmaceutical Strategies Group president, in a press release. “Affordability of specialty drugs for plans and members is driving this interest, while there is a concern about sustainability in these models.”

Insurers also gave a mixed review to copayment assistance programs, which offer coupons and other discounts to consumers to cover the cost of high-price drugs. Most (70%) said they were necessary to assist people in affording high-cost medications, however, 68% said that these programs encourage patients to take pricier brand-name drugs rather than select the lower-cost alternative medication.

Given the growing number of specialty drugs with eye-popping prices, costs in this area are a major concern for employers and payers in the long and short term, according to the survey. For instance, less than a quarter (24%) of those surveyed currently had a member taking a gene therapy drug, but 81% expect the affordability of these products to be a significant or moderate challenge in the next two to three years.

Insurers said the biggest concern in this space is ensuring parity in costs across both the medical benefit and pharmacy benefit, according to the survey, while employers said the largest hurdle is the affordability of cost-sharing for members. Due to their size, large employers are better positioned to manage these expenses, the survey said.

As these drugs grow in number, value-based contracts will prove vital, said Renee Rayburg, vice president of specialty at the Pharmaceutical Strategies Group, in the release.

“Rare disease treatments that are being targeted by cell and gene therapies will drive future spending,” Rayburg said. “[Value-based contracts] represent an effort into finding strategies for keeping costly specialty drugs accessible and affordable.”

However, as evidenced by the low uptake of value-based contracting found in the study, disrupting the existing paradigm is difficult. Just under half (49%) of those surveyed said they support eliminating rebates and instead deploying upfront discounts, down from 64% who said the same a year ago.

Most (95%) of the surveyed payers use prior authorization for these drugs, and 85% said they can track and report on their approval and denial rates, up from 66% in 2022. More than half (54%) said they have prior authorization in place for a branded drug that has a biosimilar available, and 51% said they use step therapy, which would require a patient to try a biosimilar first.

Sixty-two percent of those surveyed, however, said they were moderately or greatly concerned about the potential for unintended consequences related to prior auth, such as member dissatisfaction or care delays.

The hottest topic in the media these days is Artificial Intelligence (AI). It seems like everyone is talking about it. But that may be short sighted if you are neck deep into specialty pharmacy.

We’ve sent several reports recently on gene therapies because it is rapidly becoming ‘the next big thing’ in medicine. Analysts say that by the end of 2024 about 20 cell therapy launches and as many as 30 gene therapy launches are expected.  Oh MY!

Within the past few days, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee voted to back accelerated approval for SRP-9001 for patients with Duchenne muscular dystrophy with a decision due before month’s end. Such approvals are remarkable as these new ‘wunderkind’ therapies started to sprout a only a short time ago. 

So, what is the impact of these ‘one and done cures’? Our conclusion is that the specialty pharmacy model doesn’t coexist well at all. To date, SPs have had not role in dispensing or even distributing gene therapies given the hospital-based process to harvest patient samples for the brewing of the ultimate patient/genetically specific elixir.  Oh MY! Oh MY!

If you are interested in a basic primer around gene therapy CLICK HERE

If you are curious about how many gene therapies have been approved as of 4/2023 CLICK HERE

If you would like to see what others are saying about commercializing specialty drug cell andgene therapies CLICK HERE

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Critical Success Factors for Commercializing Specialty Drugs, Cell and Gene Therapies

Although payers have become somewhat accustomed to the high cost of specialty drugs, the price tags for gene therapies are causing “sticker shock.”

Apr 17, 2023 — Specialty product innovation is increasingly viewed as a journey that begins during pre-commercialization and continues throughout the product life cycle. Pharmaceutical and biotechnology manufacturers now recognize the need to develop, implement and refine a process-driven strategy that is built upon solid structural dynamics and a proactive approach for every phase of commercialization, spanning ideation, clinical research and development (R&D), clinical trials, product launch, market access, distribution and beyond. This strategic foundation gives life sciences companies and their people a clear pathway and focus to ensure that tasks and projects are aligned across teams and departments.

With the development of a potential new specialty drug, cell or gene therapy (CGT) typically requiring a decade or longer, there are critical success factors along every iterative step of the product life cycle that all point toward the same goal: achieving market dominance and capturing substantial market share. .

…………..CLICK ABOVE to access the full article

The FDA recently approved a new subcutaneous specialty therapy, Uzedy (risperidone) from TEVA and MedinCell, an atypical antipsychotic indicated for the treatment of schizophrenia in adults.

It may be surprising that we are reporting on a recent drug approval that was originally FDA approved 30 years ago….. yep, 1993. However, the new and improved Uzedy is a possible game changer for patients with schizophrenia. Till now, patients were prescribed either oral risperidone administered daily or intramuscular injections.

Sticking to the prescribed dosing for risperidone has been a huge challenge for patients with schizophrenia. However, Uzedy is now extended release with either monthly or bi-monthly dosing….. and, is also sub-q which makes this formulation much more patient friendly. The company said 3.5 million people in the U.S. are currently diagnosed with the condition and approximately 80% of patients experience multiple relapses over the first five years of treatment usually coupled with therapy discontinuance. 

Uzedy will be available in the U.S. in “the coming weeks” at a wholesale cost of $1,232 to $3,080 per month, depending on the dosage strength (on par with other IM versions of risperidone). Other injectable forms of risperidone are available at retail so it is likely that Uzedy will similarly be open access.

CLICK HERE for prescribing information

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New treatment provides adults living with schizophrenia a long-acting formulation that offers flexible 1- and 2-month dosing intervals

In a Phase 3 clinical trial, UZEDY demonstrated up to 80% reduction in risk of schizophrenia relapse versus placebo1

UZEDY is a subcutaneous injection from a pre-filled syringe with a 21-gauge needle

APRIL 28, 2023 PARSIPPANY, N.J., TEL AVIV & PARIS–(BUSINESS WIRE)– Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA), and MedinCell (Euronext: MEDCL) announced today that the U.S. Food and Drug Administration (FDA) has approved UZEDY (risperidone) extended-release injectable suspension for the treatment of schizophrenia in adults. UZEDY is the first subcutaneous, long-acting formulation of risperidone that utilizes SteadyTeq™, a copolymer technology proprietary to MedinCell that controls the steady release of risperidone. Therapeutic blood concentrations are reached………………..

Click Here to access the full TEVA press release

We’ve reported several times on the disparity of specialty drug pricing based on where the drugs are administered. None of our readers would be surprised that significant pricing disparity continues in the marketplace and that pricing, in declining order, is most costly at hospitals, then physician practices and finally at specialty pharmacies.

None the less, it is good to keep tabs on exactly how broad the disparity is today. A new survey released by AHIP has updated stats on a basket of ten leading specialty therapies that include the following….. Darzalex, Keytruda, Lucentis, Ocrevus, Opdivo, Orencia, Prolia, Remicade, Rituxan, and Tecentriq. 

Key findings:

• On average, physician offices marked up drug prices over the price charged by a specialty pharmacy by $1,559 (+23%) and hospitals applied a markup of $8,278 (+118%). 
• The percentage of markup varied a lot on a drug by drug basis but in all cases hospitals charged the most followed by physician practices. 

It should not be a surprise that the American Hospital Association (AHA) would fire back questioning the accuracy of the article and the study as “fraught with half-truths and methodological flaws.” Yet, the AHA response pivoted saying, “High and rising drugs prices, as well as unaffordable cost-sharing requirements imposed by health plans, put considerable strain on patients and hospital resources. These resources hospitals need to deliver a wide range of high-acuity services that only they can provide, as well as to continue serving as the only site of care that treats all patients regardless of ability to pay,” the association said. 

What the AHA is really saying is that they can push their cost of operation onto patients who, increasingly, are now paying huge $$$s through deductibles and coinsurance for hospital administered and dispensed drugs.

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How Specialty Pharmacies Compare to Provider, Hospital on Drug Pricing

Drug pricing is a major concern among employers and insurers, but research has highlighted a possible price control mechanism.

April 17, 2023 – AHIP released updated data on drug pricing increases, comparing hospital costs and the prices that physician offices pay compared to specialty pharmacies.

The payer organization analyzed price increases for the ten drugs that are frequently delivered through specialty pharmacies. Data for these 10 drugs came from the Merative MarketScan Commercial Database. The data reflect hospital, physician office, and specialty pharmacy prices from the start of January 2019 through the end of December 2021.

The ten drugs that the payer organization assessed were Darzalex, Keytruda, Lucentis, Ocrevus, Opdivo, Orencia, Prolia, Remicade, Rituxan, and Tecentriq.

The study found that drugs were less costly for patients when payers leveraged a specialty pharmacy. On average, physician offices marked up drug prices by $1,559 and hospitals applied a markup of $8,278.

“Specialty pharmacies lower a patient’s health care costs by preventing hospitals and physicians from charging exorbitant fees to buy and store specialty medicines themselves,” the study explained. “Secure, direct delivery is more efficient and effective and reduces health care costs.”

In a hospital setting, the cost of drugs was, on average, around $8,200 higher than it would be if the drugs were obtained through a specialty pharmacy. Hospitals charged 118 percent more than specialty pharmacies for the same drugs.

The difference in physician offices was not as stark but remained significant. In physician offices, the same drug could cost $1,500 more than it would through a specialty pharmacy. Drug prices in physician offices were 23 percent more than specialty pharmacies’ prices.

Prolia, a treatment for osteoporosis, saw the most dramatic price difference when comparing physician office and hospital drug prices to specialty pharmacy drug prices. In the hospital setting, the price of Prolia was 212 percent of the cost through a specialty pharmacy or $2,795 more. The drug price was 49 percent higher than specialty pharmacies in the physician office setting or $651 more.

The hospital price was closest to the specialty pharmacy price for the drug Ocrevus, a therapy for multiple sclerosis. But even in this case, the hospital price was 65 percent higher than the specialty pharmacy alternative and the markup was worth $22,078, which is more than any of the other markups.

Among physician offices, the price difference was smallest for Remicade, which treats Crohn’s Disease and psoriasis, and Rituxan, which treats rheumatoid arthritis. Physician offices priced these drugs six percent higher than specialty pharmacies. Nevertheless, the small markups were still worth hundreds of dollars. Physician offices marked up Remicade by $277 on average and Rituxan by $579.

“Specialty pharmacies improve health care affordability while protecting patient safety. AHIP encourages lawmakers to support the use of specialty pharmacies, and to reject policies that take away lower-cost choices from patients,” the study concluded.

Payers have turned increasingly to specialty pharmacies to control rising drug costs. In November 2022, Elevance Health announced plans to acquire a specialty pharmacy that would focus on chronic disease management.

Employer groups have recommended that employers leverage specialty pharmacies to break into biosimilar adoption. At the beginning of 2023, experts anticipated that this strategy would take root.

By Kelsey Waddill, Health Payer Intelligence

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AHIP, AHA point fingers on cost of specialty drugs

Rylee Wilson

Insurer groups say hospitals are to blame for higher costs of specialty drugs, while hospitals say the problem stems from drug manufacturers and pharmaceutical benefit managers. 

In a report published April 17, AHIP found the average cost per treatment was nearly $8,300 higher for physicians-administered drugs purchased in hospitals than for drugs obtained through specialty pharmacies. 

AHIP’s report compared prices for the 10 physician-administered drugs that accounted for the most Medicare spending in 2020. 

“Health insurance providers are developing innovative solutions every day to make prescription drugs more accessible and affordable, and specialty pharmacies have a big role to play,” AHIP President Matt Eyles said in a April 17 news release. “They represent a safe alternative to hospital and physician purchased drugs that can boost access and affordability for all Americans.”

Specialty pharmacies handle drugs for rare or chronic conditions not stocked in retail pharmacies. These medications often have high prices. 

PBMs often operate their own specialty pharmacies. 

In an April 25 blog post, the American Hospital Association said AHIP’s report is “fraught with half-truths and methodological flaws.”

In the post, the association said AHIP’s report does not take into account safety issues that can arise from “brown-bagging” or “white-bagging” drugs, where patients receive medications from a specialty pharmacy and must bring them to their physician to be administered. 

The AHA also criticized AHIP’s methodology, writing that AHIP drew “sweeping conclusions” from a review of just 10 drugs. 

The blame for high prices rests with drug manufacturers, not hospitals, according to the AHA. 

“High and rising drugs prices, as well as unaffordable cost-sharing requirements imposed by health plans, put considerable strain on patients and hospital resources. These resources hospitals need to deliver a wide range of high-acuity services that only they can provide, as well as to continue serving as the only site of care that treats all patients regardless of ability to pay,” the association said in the blog. 

“Neither health insurers, nor their PBM and specialty pharmacy affiliates, have any such obligation to their communities,” the AHA added.

The FDA recently approved a new gene therapy, Omisirge (omidubicel-onlv) from Gamida Cell Ltd., for use in adult and pediatric patients (12 years and older) with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection. 

Approval was granted with a Boxed Warning for fatal or life-threatening infusion reactions, graft versus host disease (GvHD), engraftment syndrome and graft. Such adverse reactions are similar to other approved unmanipulated cord blood (UCB) products.

The recommended course of therapy for Omisirge is a single dose for infusion provided by the manufacturer as 2 separate components (CF and NF). Omisirge CF and Omisirge NF are infused one after the other once the patient has received an appropriate conditioning regimen. Each Omisirge unit is specific to each patient. 

The company indicated that Omisirge will be available in the United States to transplant centers for appropriate patients.  Gamida Cell did not offer details as to distribution logistics.

CLICK HERE for prescribing information

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FDA approves Omisirge to reduce time to neutrophil recovery and infection in patients with hematologic malignancies

On April 17, 2023, the Food and Drug Administration approved omidubicel-onlv (Omisirge, Gamida Cell Ltd.) for use in adult and pediatric patients (12 years and older) with hematologic malignancies who are planned for umbilical cord blood transplantation following myeloablative conditioning to reduce the time to neutrophil recovery and the incidence of infection.

Safety and efficacy were evaluated in Study P0501 (NCT02730299), an open-label, multicenter, randomized trial of omidubicel-onlv transplantation or unmanipulated cord blood (UCB) unit transplantation following myeloablative conditioning in patients with hematologic malignancies. In total, 125 patients were randomized–62 patients to receive omidubicel-onlv and 63 to the UCB group. Fifty-two patients were transplanted with omidubicel-onlv receiving a median CD34+ cell dose of 9.0 X 106 cells/kg (range 2.1 – 47.6 X 106 cells/kg). Fifty-six patients were transplanted in the UCB arm with one or two cord units (66% received two cord units). In the 42 patients with reported post-thaw cell dose, the median CD34+ cell dose was 0.2 X 106 cells/kg (range 0.0 – 0.8 X 106 cells/kg). Multiple conditioning regimens were used, including Total Body Irradiation-based or chemotherapy-based options.

The main efficacy outcome measures were time to neutrophil recovery following transplantation and the incidence of Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Grade 2/3 bacterial or Grade 3 fungal infections through Day 100 post transplantation. The median time to neutrophil recovery was 12 days for those receiving omidubicel-onlv (95% CI: 10-15 days) and 22 days in the UCB arm (95% CI: 19-25 days). Eighty-seven percent in the omidubicel-onlv arm and 83% percent in the UCB arm achieved neutrophil recovery. The incidence of BMT CTN Grade 2/3 bacterial or Grade 3 fungal infections through Day 100 post transplantation was 39% and 60%, respectively, in the two groups.

Among 117 patients who received omidubicel-onlv for any disease, infusion reactions occurred in 47% of patients, acute GVHD in 58%, chronic GvHD in 35%, and graft failure in 3%.

In patients with hematologic malignancies in Study P0501, the most common Grade 3-5 adverse reactions were pain (33%), mucosal inflammation (31%), hypertension (25%), and gastrointestinal toxicity (19%).

The recommended omidubicel-onlv dose is two sequential infusions consisting of:

a Cultured Fraction: a minimum of 8.0 × 108 total viable cells with a minimum of 8.7 percent CD34+ cells and a minimum of 9.2 × 107 total CD34+ cells, followed by

a Non-cultured Fraction: a minimum of 4.0 × 108 total viable cells with a minimum of 2.4 × 107 CD3+ cells.

This application was granted priority review, breakthrough designation and orphan drug designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

What do ‘ya get from a DNA modified pig?

…………. wait for it………………..

           ………….wait for it………………..

…………………..CRISPR BACON! 😊

DNA modification is about to trigger a tsunami level change in the pharmaceutical world. New products are already marching towards approval and, with proof of concept, the wave will predictably build rapidly.

Specialty pharmacy is in the bullseye for CRISPR sequenced therapies since  many of the therapies under the SP umbrella target genetic illnesses. Early research using CRISPR based technology has focused on hematologic conditions that are currently served by specialty pharmacies with drugs that only treat symptoms.

Will specialty pharmacies have a role in the emerging CRISPR world? Maybe.

These next-gen, DNA modified therapies will logistically resemble recently approved last-gen gene therapies. Current gene therapies are uber expensive and require hand holding throughout the patient journey. Hence, the arrival of the rare disease pharmacy.

But the new therapies won’t necessarily be limited to ultra-rare orphan conditions. If the therapies are highly efficacious, i.e., cures,  then the need for dispensing may disappear completely and the pharmacy relationship would transition to distribution (to the physician / hospital), patient monitoring and data capture. With fewer and fewer patients requiring treatment over time, the need for multiple dispensing specialty pharmacies would likely diminish as well. So, the role of the specialty pharmacy industry as we know it may be tenuous.

Read the interview below for some great insights into the next generation of pharmacy.

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Has the CRISPR revolution arrived yet?

A decade after scientists developed the ability to edit DNA using the CRISPR sequence, the first drugs using the technique are approaching the market, with the potential to transform the lives of people with certain genetic illnesses. But questions of ethics, access, and pricing remain. We talked with Dr. Greg Licholai, a biotech entrepreneur and a lecturer at Yale SOM, about the state of the technology.

Q: What is the state of CRISPR right now?

There have been a lot of developments. We’re on the verge of having the first CRISPR-based drugs approved, and there’s a whole pipeline of new therapies on the way. A Noble Prize has been awarded and patent battles between Berkeley and MIT have been settled. Also, there’s been a major controversy in terms of human experiments and ethical transgressions resulting in a scientist going to jail for experimenting on human embryos. So it’s been pretty dramatic and it continues to be.

Q: We last spoke about CRISPR in 2018 . Has the amount of change in the last five years been what you expected? Has it been in the direction you expected?

It’s about on pace to get from lab experiments to being on the verge of getting a drug approved—that’s a pretty good timing. The pipeline is clustered around hematologic disorders, so perhaps I might have expected there to be more progress in other diseases, but it’s about on pace.

Q: How far are we from having CRISPR-based drugs in the pharmacy or in a doctor’s toolkit?

It’s very exciting. We’re very close.

The drugs that are nearest for approval are being co-developed by Vertex Pharmaceuticals and CRISPR Therapeutics, and they’ve collaborated on a product called Exa-cel, which is for sickle cell anemia and beta thalassemia, two blood disorders. They presented the results at the end of last year at major hematology conferences, and they’re planning to submit the BLA, which is the licensing application to the FDA this year. It takes about nine months or a year to go through the process, so we could see the first therapeutic approved at the end of this calendar year.

Q: What kind of impact would you expect for someone with sickle cell anemia? Is this an incremental change? Is this a big change?

It would be a huge, sweeping, revolutionary change, with the potential of giving a single dose of a drug and changing the way these patients produce their own blood cells so that they’d be potentially cured of the disease.

It would have the effect of doing a bone marrow transplant, which is done in cancer centers, and is high risk and very difficult for patients. CRISPR would be much easier and better tolerated. With CRISPR doctors take blood cells, use CRISPR technology to alter the defective genes, and the reinfuse the new and improved cells, which go on to produce healthy red blood cells in the patient. In sickle cell anemia, patients have a pain crisis because the cells have a problem with their morphology. Beta thalassemia is a type of anemia, and similarly, the red blood cells have a genetic problem with their ability to carry hemoglobin. The preliminary data from 31 patients suggests that a course of treatment may cure the disease. So it’s a very dramatic improvement.

Q: What do you foresee as the accessibility of these kinds of therapies? Are the prices extremely high? Will insurance cover them? Will there be economic or racial disparities in access?

The science has progressed. However, what’s lagged are the regulatory standards and any conclusions about pricing as well as improved access to novel therapies. There just hasn’t been guidance established yet. So we’ll have to wait to see about that.

The pricing question could be dramatic. Previously approved gene therapies are incredibly expensive, over $1 million, sometimes close to $3 million. This is because the argument from the pharmaceutical manufacturer is that typically drugs need to be given repeatedly, so they expect long-term sales. But with the ability to give a single dose and cure a patient, companies say they’ll never recoup their R&D investment, especially in rare diseases.

So their argument is essentially, “Look, the system would be paying more over the life of the patient. We’re just bringing the payment upfront.” Because these drugs have not been approved yet, we don’t know what pricing assumptions that the companies will make, but I’m sure they’re struggling with those questions right now.

On the regulatory front, that’s another unknown because every time a new class of biology goes to the FDA, they have to determine the best way to study safety and effectiveness. A single dose drug that affects somebody’s entire life raises questions about the appropriate timeline to monitor safety events. It also raises important questions about potential effects for not just this individual, but perhaps their children. So how long do you monitor before you say, “OK, the safety portion of the trial has been concluded and we feel comfortable with that”? Those decisions have yet to be codified as standards..

Q: You mentioned that the focus has been in the hematological area. Are there other diseases that theoretically could be addressed in the same way but are further back in the pipeline?

There’s another rare disease called A-1AT, which is Alpha-1 antitrypsin deficiency. That’s in early stage development. It’s a combination pulmonary and liver disease. There’s another one in development for a rare condition called hereditary angioedema, plus some others that are earlier in the pipeline.

The critical issue is getting enough of the CRISPR drug into the cells that need to be altered so that you can have the beneficial effect for the patient. For some of these, like A-1AT, you’d want to be targeting the liver, and it’s a little bit easier to give an infusion since drugs go straight to the liver and they get distributed appropriately. But when other organs are involved, that would be a lot more challenging to get a wide distribution of a CRISPR drug, or a gene therapy or even regular drugs. For instance, getting into the brain and getting broad distribution of a complicated drug like this would be challenging.

Q: Five years ago, we talked about the possibility of making a genetic change to avoid a disease entirely when someone is still an embryo. Is that still a possibility?

There have been genetic animals produced using CRISPR through that method. There have been CRISPR modified pigs and even cows. By far the most frequent use of CRISPR right now is to produce genetically modified mice for lab experiments. In the past, this was a time-consuming thing where researchers would have to create a “knockout mouse”—they would try to insert a gene into the mouse’s genome—and it was very hit or miss. Now it’s become almost routine to produce these genetically altered CRISPR mice for research purposes.

So we know it’s theoretically possible to do all this in mammals. There’s famous, highly controversial and unethical work that was done by a researcher in China, who altered the embryos of human babies in order to prevent them from acquiring HIV from a parent. When that researcher announced results, there was global backlash, including from China, the scientist’s home. He was sentenced to three years in jail. I believe they reacted appropriately by condemning that use of human embryos. There continues to be a moratorium on human experimentation.

Q: What about using gene editing on animals to prevent the spread of animal-borne diseases?

It continues to be possible, but there remains to be a lot of caution about doing that, which is appropriate. The big concern is that altering an animal’s genes may change their reproductive cells, leading to new genetic lines with mutations that may be introduced into the population and have unknown consequences. That’s possibly the biggest long-term concern.

Q: You mentioned a few risks and ethical concerns. Would you talk about risks in general and where the balance is in terms of risk and benefit at this point?

The biggest risk is that the CRISPR edits cause a germline mutation, which is the reproductive cell mutation, and those altered genes are get transferred to offspring and an entire population with unknown consequences. There’s an absolute moratorium on doing that in human beings. So that is currently a theoretical risk, and I do trust researchers and drug companies to honor those boundaries.

However, there’s a theoretical possibility that infusing CRISPR-altered cells as stem cells could have other unknown consequences, perhaps germline, perhaps other things. There’s only a small possibility that it’ll happen, but it should be monitored. There is also the possibility that the genetic benefits will not last the expected duration or patients’ lifespans. So patients will have to be monitored to be confident that lifelong benefit are achieved as well as avoiding risks.

Q: What are the other open questions being discussed in and around CRISPR?

I think the biggest question is around the business model and whether society will accept extremely expensive single-dose drugs for rare conditions, and whether payers or governments will pay. Ultimately, if there’s a contraction in the willingness to pay for these types of novel, very expensive therapies, it’ll be difficult for biotech companies to be funded. But it’s a business risk that probably the biggest pharmaceutical companies are going to be cautious about entering into until they see economic validation plus scientific proof of concept.

Provided by Yale University by Ben Mattison, Yale University

Credit: CC0 Public Domain

This week the FDA approved a new therapy, Qalsody (tofersen) from Biogen MA, Inc., for the treatment of amyotrophic lateral sclerosis (ALS) in adults who have a mutation in the superoxide dismutase 1 (SOD1) gene. Continued approval for this indication is contingent upon providing more data on the drug’s effectiveness and clinical benefit in confirmatory, post-launch trial(s).

Qalsody is the first available treatment targeting a genetic cause of the disease. Approval is based on trial data that showed it reduced levels of neurofilament protein, an indicator of nerve cell degeneration believed to be tied with disease progression. 

According to the CDC, between 16,000 and 32,000 Americans are currently living with ALS. Approximately 2% of ALS cases are associated with mutations in the SOD1 gene. The agency estimates there are fewer than 500 patients with SOD1-ALS in the United States.

Qalsody is administered by intrathecal injection by a trained health care provider. Patients receive three initial doses administered at 14-day intervals, followed by a maintenance dose every 28 days.

Biogen confirmed that it expects to launch Qalsody on par with other ALS therapies on the market. Relyvrio, approved for ALS in 2022, costs about $158,000 annually, while older Radicava costs about $170,000 annually.

Qalsody is likely to launch through specialty pharmacy distribution given its cost, very small patient population and requirements to capture real-time clinical data.

CLICK HERE for prescribing information

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FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene

04/25/2023 — FDA approved Qalsody (tofersen) to treat patients with amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase 1 (SOD1) gene (SOD1-ALS). Qalsody is an antisense oligonucleotide that targets SOD1 mRNA to reduce the synthesis of SOD1 protein. The approval was based on a reduction in plasma neurofilament light (NfL), a blood-based biomarker of axonal (nerve) injury and neurodegeneration. 

Disease or Condition

Similar to sporadic ALS, where there are no associated risk factors and no family history of the disease, SOD1-ALS is a progressive neurodegenerative disease that attacks and kills the nerve cells that control voluntary muscles. Voluntary muscles produce movements such as chewing, walking, breathing, and talking. ALS causes the nerves to lose the ability to activate specific muscles, which causes the muscles to become weak and leads to paralysis.

Effectiveness

The effectiveness of Qalsody was evaluated in a 28-week, randomized, double-blind, placebo-controlled clinical study in 147 patients with weakness attributable to ALS and a SOD-1 mutation confirmed by a central laboratory. The study randomly assigned 108 patients in a 2:1 ratio to receive treatment with either Qalsody 100 mg (n = 72) or placebo (n = 36) for 24 weeks (three loading doses followed by five maintenance doses).

The participants were approximately 43% female; 57% male; 64% White; and 8% Asian. The average age was 49.8 years (range from 23 to 78 years).

Patients receiving Qalsody had nominally significant reductions in plasma NfL concentration at Week 28 compared to the placebo arm. The findings are reasonably likely to predict a clinical benefit in patients. The observed reduction in NfL was consistent across all subgroups based on sex, disease duration since symptom onset, site of onset, and use of other medications for ALS treatment.

Qalsody is approved under the accelerated approval pathway, under which FDA may approve drugs for serious conditions where there is an unmet medical need and a drug is shown to have an effect on a surrogate endpoint that is reasonably likely to predict a clinical benefit to patients. To confirm the clinical benefit of Qalsody, a Phase 3 randomized, double-blind, placebo-controlled trial is ongoing in individuals who are carriers of the SOD1 genetic mutation who do not yet have symptoms. The study will assess the proportion of individuals treated with Qalsody who develop symptoms of ALS during the trial compared to placebo. 

Safety Information

The most common side effects were pain, fatigue, arthralgia (joint pain), increased cerebrospinal (brain and spinal cord) fluid white blood cells, and myalgia (muscle pain).

Designations

Qalsody received priority review, orphan drug and fast track drug designations.

Most would agree that the US has been a litigious-heavy country for decades. As we know, healthcare is one of the biggest targets for lawsuits of every complexion. And under the healthcare umbrella, pharmacy follows physicians and hospitals as a major target for litigation.

We’ve seen lots of lawsuits filed by patients claiming harm following a refill with a generic drug switched at the pharmacy from their beloved brand name product. However, the article below details the case of a patient claiming harm when their generic drug was dispensed by the same generic drug….. but from a different manufacturer. Who’d a expect that?

One reason that we are covering this lawsuit in today’s Report is that the pharmacist and even the pharmacy technician were named in the suit. The pharmacist and technician were eventually released from the suit but experienced the hassle and expense of mounting a defense. Also not good PR in the media.

Specialty pharmacies should always be on the watch for potential litigation. The case below is a learning experience for SP management and should be shared with pharmacy legal counsel.

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Patient Files Negligence Suit After Receiving a Different Generic Version

Apr 24, 2023

Individual alleges that an equivalent product from another manufacturer precipitated series of seizures.

Issue of the Case

A patient who presented a prescription for dispensing received an equivalent product from a different manufacturer and alleged that a series of seizures resulted from the change. Will she prevail in her negligence lawsuit against the pharmacy?

Facts of the Case

The patient had been taking the antiseizure medication levetiracetam for 10 years, always receiving it in a form described as yellowish white. She presented a new prescription at a chain pharmacy and received a pink version of the medication. She asked the pharmacist whether this new version would be safe to use; he told her it would.

After starting to use the new version, the patient experienced 3 seizures, which led to her being admitted to the hospital. This was cause for concern, because she had been using the yellowish-white version for 10 years and had not had a seizure for 7 years.

She filed a lawsuit against the pharmacy, the pharmacist, and the pharmacy technician involved in dispensing the medication. The patient subsequently added the manufacturer of the pink dosage form as a defendant.

The patient’s attorney advanced several legal theories as the basis for liability and made submissions to the state trial court that had jurisdiction. A total of 4 amended complaints were submitted on behalf of the patient as the matter progressed. As is sometimes appropriate, a complaint would be submitted and rejected by the court but with authorization to revise it and resubmit. Through this process, the pharmacist and technician were deleted as defendants, but the matter was decided as amended against the pharmacy chain and the manufacturer.

The trial court judge received a motion from the attorneys for the defendants to dismiss the lawsuit and reviewed the legal arguments and theories advanced by the attorneys for the patient. All arguments were rejected and the lawsuit was dismissed. The plaintiff appealed to the state’s appellate court.

The Ruling

The appellate court reviewed the various arguments of the plaintiff and the lower court judge’s decisions. All decisions were affirmed on appeal. The matter was dismissed.

The Court’s Reasoning

The negligence claim advanced by the plaintiff argued that the pharmacy had a legal duty to dispense the medication without a change in source, as well as to warn of potential dangers associated with the version dispensed. The pharmacy chain responded that the prescription was issued using generic product identification and that the various expectations found in the state’s drug product selection statute, which were the basis for the plaintiff’s arguments, did not apply. Moreover, the chain argued that any duty to warn of danger associated with the medication rested with the prescriber under the learned intermediary doctrine. The appellate court agreed with the pharmacy chain.

Next, the patient’s allegation that the pharmacist’s response that use of the different version of medication would be OK did not give rise to any legal duty on the part of the pharmacist or pharmacy in the view of the appellate court judges.

The plaintiff’s attorneys also argued that the pharmacy had a legal duty to dispense the medication without changing the source. The court agreed with the pharmacy chain that because the prescriber had not marked the portion of the prescription form that read “DAW [dispense as written]: No product selection indicated,” that interchange of product source had not been prohibited by the prescriber.

In another revision, the plaintiff argued that the sub potency of the dispensed product resulted in it being considered adulterated. That led to the argument that the pharmacy had been negligent because of obtaining tablets in an adulterated state that were initially made in a form less than 500 mg. The pharmacy chain responded that it was not the manufacturer of the dosage forms and thus the plaintiff should not prevail with this argument. The court agreed.

The manufacturer of the tablets that had been dispensed argued that the FDA had found its version to be therapeutically equivalent to the product the patient had originally received. If there were a difference in therapeutic effect, the sole enforcement authority for that rested with the FDA under a specific provision in the relevant federal statute. The trial court judge dismissed that argument by the plaintiff, and the court of appeals affirmed it.

Finally, the plaintiff had argued that the pharmacy knew about the purported defect in the medication dispensed and had ignored that, resulting in her injury. In response, the defendants pointed out that plaintiff had been in possession of the allegedly subpotent dosage forms for more than 2 years with an opportunity to examine the chemical composition of the tablets. The plaintiff had never allegedly pursued such testing and had made no direct allegation of a defect existing in the dosage forms.

In conclusion, the court of appeals rejected all arguments advanced by the plaintiff in the various amended complaints, affirmed the decisions of the trial court, and, overall, affirmed dismissal of the lawsuit.

About the Author

Joseph L. Fink III, JD, DSS (Hon), BSPharm, FAPHA, is professor emeritus of pharmacy law and policy at the U of Kentucky College of Pharmacy in Lexington.

Pharmacy Times

The article below is one that a specialty pharmacy’s legal counsel might find most interesting. In short, the US District Court ruling below said that Humana could not pursue RICO charges against Biogen and ACS Pharmacy because it did not have standing in the matter. Humana would have needed to be the “purchaser” to have standing and the court deemed it was only the “payer”.  Hmmmm

The difference between purchaser vs. payer may be difficult for the non-legal-eagles in our midst to fully fathom. But it does clarify how the courts perceive the manufacturer and the specialty pharmacy in these instances. And, ultimately, specialty pharmacies can face a much bigger legal hill to climb if charged with a RICO violation.

Fortunately for the industry, there have been fewer legal black-eyes related to financial shenanigans by specialty pharmacies in recent years. That’s good for the industry especially in a reactionary legislative environment.

Click here to read the full text of the opinion.

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RICO – Standing – Indirect Purchaser

U.S. District Court

By: Mass. Lawyers Weekly Staff April 6, 2023

Where a plaintiff insurance company has filed a complaint under the Racketeer Influenced and Corrupt Organizations statute alleging that the defendant made unlawful charitable donations to fund patient copays of its multiple sclerosis drugs, the defendant’s motion to dismiss should be allowed because the plaintiff is an indirect purchaser of the pharmaceutical products at issue, so it does not have standing to assert a civil RICO claim.

“This is an action arising out of an alleged scheme to increase the number of prescriptions of drugs used to treat multiple sclerosis (‘MS’) through improper charitable contributions. Plaintiff Humana, Inc. is a health-insurance company. Defendant Biogen, Inc. is a biotechnology company and manufacturer of three different drugs used to treat MS. Defendant Advanced Care Scripts, Inc. (‘ACS’) is a specialty pharmacy company. According to the complaint, Biogen made unlawful donations to different charities to fund patient copays of its MS drugs, thereby increasing the sales of those drugs.

“… Although Humana was the ultimate payor of the prescription drugs at issue — putting to one side the requirement of a patient copay — it did not purchase the drugs directly from Biogen. Instead, it paid pharmacies for the drugs, who had purchased the drugs from wholesalers or distributors (or possibly from Biogen itself). Humana was thus an ‘indirect’ purchaser.

“Under the ‘indirect purchaser rule,’ first developed by the Supreme Court in the antitrust context, only a direct purchaser of goods has standing to assert a claim for violation of the antitrust laws. Every circuit to have considered the issue has held that the rule also applies to civil RICO actions, and that indirect purchasers therefore do not have standing to assert RICO claims. The First Circuit has not yet addressed the question. While there may be practical and policy reasons to question the application of that rule in the health-insurance context, for the reasons that follow, this Court will follow the majority rule. It will therefore dismiss the civil claims for failure to state a claim on that basis. …

“Accordingly, because Humana is an indirect purchaser of the pharmaceutical products at issue in this case, it does not have standing to assert a civil RICO claim. Count 1 will therefore be dismissed.”

Humana, Inc. v. Biogen, Inc., et al. (Lawyers Weekly No. 02-154-23) (34 pages) (Saylor, C.J.) (Civil Action No. 21-11578-FDS) (March 31, 2023).