Davy James

The FDA has approved dapagliflozin (Farxiga, AstraZeneca ) to decrease the risk of cardiovascular (CV) death and hospitalization from heart failure in adults with heart failure (NYHA class II-IV) with reduced ejection fraction (HFrEF) with and without type 2 diabetes (T2D).

The approval follows positive results from the phase 3 DAPA-HF trial, in which dapagliflozin showed a statistically significant and clinically meaningful decline in CV death or hospitalization from heart failure compared with placebo. 

“The ground-breaking results of the DAPA-HF trial have transformed heart failure therapeutics,” said John McMurray, MD, Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK, in a press release. “Today’s approval provides physicians with a completely novel pharmacological approach that greatly improves outcomes for patients with heart failure with reduced ejection fraction.”

Dapagliflozin is the first sodium glucose co-transporter 2 (SGLT2) inhibitor approved by the FDA for treatment of patients with HFrEF (LVEF ≤ 40%). Earlier this year, dapagliflozin was granted Priority Review designation by FDA and Fast Track designation was granted in September 2019.

In the DAPA-HF trial, researchers found that dapagliflozin, in addition to standard of care, decreased the risk of the composite outcome of CV death or the worsening of HF versus placebo by 26% (absolute risk reduction [ARR] = 5% [event rate/100 patient years: 11.6 vs 15.6, respectively]; p<0.0001) in patients with HFrEF, according to a press release. During the trial, the investigators found 1 CV death or hospitalization for HF, or an urgent visit associated with HF could be avoided for every 21 patients treated with dapagliflozin.

The safety profile of dapagliflozin in the DAPA-HF trial was found to be consistent with the previously established profile of the drug in earlier trials. The most common adverse reactions (≥5%) associated with dapagliflozin 5 mg, 10 mg, and placebo respectively were female genital mycotic infections (8.4% vs 6.9% vs 1.5%), nasopharyngitis (6.6% vs 6.3% vs 6.2%), and urinary tract infections (5.7% vs 4.3% vs 3.7%), which were established in a pool of 12 placebo-controlled studies.

The FDA approved dapagliflozin in October 2019 to reduce the risk of hospitalization for HF in adult patients with T2D and established CV disease or multiple CV risk factors. Dapagliflozin is also indicated as an adjunct to diet and exercise to improve glycemic control in adults with T2D. Dapagliflozin is not recommended for patients with type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.

“With the approval of Farxiga, we have reached a critical milestone to potentially transform heart failure treatment for the millions of people living with the condition in the US,” said Mene Pangalos, executive vice president, BioPharmaceuticals R&D, in a press release. “We are now one step closer to making a significant impact on their lives by providing a much-needed treatment to help reduce their disease burden and live longer.”

Farxiga approved in the US for the treatment of heart failure in patients with heart failure with reduced ejection fraction [news release]. London, United Kingdom; May 6, 2020: AstraZeneca website. https://www.astrazeneca.com/media-centre/press-releases/2020/farxiga-approved-in-the-us-for-the-treatment-of-heart-failure-in-patients-with-heart-failure-with-reduced-ejection-fraction.html Accessed May 6, 2020.

Articles

A phase 3 trial showed a statistically significant and clinically meaningful decline in CV death or hospitalization from heart failure with dapagliflozin compared with placebo. 

FDA Approves Dapagliflozin for Heart Failure in Patients With Reduced Ejection Fraction

With drug pricing increasingly becoming a hot button issue and greater consternation surrounding the cost of treating a chronic disease among the general public, it is clear that the health care industry is at a crossroads.

During the featured session at the Asembia Specialty Pharmacy Summit 2019, “Specialty Industry Outlook: What’s Next,” speakers Adam Fein, PhD, CEO of the Drug Channels Institute; Lisa Gill, managing director of J.P. Morgan Securities; and Doug Long, vice president of industry relations at IQVIA, explored the radical changes that could be on the horizon from potential legislation that would dramatically alter the health care industry.

Fein pointed to the proposal from the Department of Health and Human Services that would remove safe harbor protection under the Anti-Kickback Statute for rebates on prescription drugs paid by manufacturers to pharmacy benefit managers (PBMs), Part D plans, and Medicaid managed care organizations.

“We are at an inflection point that potentially is going to change the entire commercial model of the pharmaceutical industry for the first time in probably a generation,” Fein said. “We are at a turning point that 3 years ago I didn’t even think was possible. We are potentially on the verge of moving to a world without PBM rebates, a total change in all the ways that we do business.”

Fein noted several factors that have contributed to what would be a dramatic shift in the way that health care is funded, which began to gain steam following the price increase for the EpiPen, garnering scrutiny in the media and from legislators. He said the gross-to-net bubble— a term developed by the Drug Channels Institute to describe the profit between the list price a manufacturer sets for a drug and the net price after rebates and other reductions&mdash;has continued to inflate and has caused a multitude of problems with the US drug pricing system.

“What happened is we have this giant gap between the list, or gross price, and the actual price that is received by the manufacturer,” Fein said. “Some categories are so broken that the gap between the list and the net is 80% or 90%. The net price received by  manufacturers is growing in [the] low single digits.” The inflation of this bubble has led to 3 elements that are creating a growing crisis for patients, according to Fein.

The first element is that the amount in spending either on coinsurance or a deductible is now more than 50% of the total that patients pay out of pocket compared with 15% to 20% a decade ago, according to Fein.

“Patients can be in the deductible and not be able to afford their insulin because they have to pay the full price,” he said. “That is a travesty, and it’s been a travesty of benefit design where we’ve shifted cost to people who maybe don’t need motivation to have skin in the game. If you have cancer, you don’t need motivation to take your medicine. Making it essentially unaffordable through benefit design is, I think, cruel. It doesn’t make any sense to me.”

The second element is a factor Fein called reverse insurance, which runs counter to normal insurance, in which healthy people pay premiums for services they may not need in order to subsidize the sick.

“What’s happening now with the gross-to-net bubble is the reverse of that,” he said. “If you are chronically ill, if you have a serious condition that’s generated a lot of rebate dollars, you may be forced to pay a very high price for that drug. The money that you’re contributing is used to lower the premiums of the healthier people.”

The third element is what Fein called warped incentives, in which all parties in the health care system want list prices to go higher.

Despite the speculation that has surrounded the rebate rule, during her presentation, Gill said Wall Street does not expect major changes in the short term. “We’ll probably have some types of programs that will happen,” she said. “I agree that the world will change, but I really do believe there’s still a great opportunity for the PBM industry to help to manage this.”

Gill said that the real value of PBMs is to drive patients to the right drug, which the government has started to appreciate. “I do think that PBMs have a real place in the marketplace to drive clinical protocols and to drive clinical outcomes,” she said. “Even if we don’t have rebates, I still think at the end of the day, you’re going to need someone to negotiate based on the size and scale of the marketplace.”

She added that the persistent challenges in the current health care model have created a situation in which the consumer is becoming the biggest disrupter in health care. “[A] plan design has not been put in place with the thought around how [this affects] somebody’s out-ofpocket costs, and those patients now are getting more involved in their health care decisions,” she said. “They are making more of those decisions because they’re paying more out-of-pocket dollars.”

Gill said that convenience, quality, and cost will be the key drivers of this disruption, as she warned that a shift to value-based care must come to fruition and that the companies that are part of the solution to this shift will reap the greatest long-term benefits.

“I had a great conversation with a health care leader last week where he said to me, ‘Lisa, we’re going to have Medicare for all 10 years from now if we do not move our health care system toward value-based care,’” she said. “The perverse incentives of the way our health care system works today will not last.”

During his portion of the presentation, Long provided an overview of trends and an outlook for the future of the US pharmaceutical market. He outlined the major forces that are combining to drive the desire for change in the health care system.

These forces include the increasing cost for care and the growing scrutiny surrounding value, which have prompted a reassessment of the payer role and new sustainable models as patients become more involved in health care decision making due to the challenges created for the entire system from lack of adherence.

“During the deductible period, the patient is more likely to abandon their medication,” Long said. “Twenty-seven percent of the time they will abandon a specialty drug during the deductible period. That’s why co-pay cards are so important. People are going to say, ‘It’s just not worth it to me to take my medication.’”

With a clear need for changes to the health care system to protect patients, the panelists agreed that the current model is reaching a tipping point that could lead to a tectonic shift in care management.

“This is probably a time of greater change than I’ve ever seen in this industry,” Fein said. “My final piece of advice to you with all this change, with all this trouble, with all this complexity, is please try to stay positive and, as always, test negative.” 

For more on the implications of the elimination of rebates, visit drugchannels.net/2019/03/a-worldwithout-rebates-predictions-for.html. 

With drug pricing increasingly becoming a hot button issue and greater consternation surrounding the cost of treating a chronic disease among the general public, it is clear that the health care industry is at a crossroads.


Massive Change Could Be Looming for Specialty Pharmacy

Although the general public commonly associates specialty pharmacy with the dispensing of high-cost drugs, the emerging "specialtylite" model is challenging that narrative by involving the same robust level of services and support at a much lower price point for the medications.

The "specialty-lite" platform leverages the current infrastructure of specialty pharmacies with efficient services and emerging technological solutions that focus on ensuring prescription fulfillment with economic feasibility. During the session “Specialty Lite: An Evolving Fulfillment Model” at the Asembia Specialty Pharmacy Summit 2019, speakers Snehal Patel, PharmD, vice president of pharmacy and access solutions, Asembia, and Tony Lanzone, partner, Corsica Life Sciences, LLC, discussed the growth of specialty lite and its potential to improve fulfillment and adherence via a comprehensive set of services.

The speakers noted that experience with the complex requirements for specialty patient support combined with emerging technology have made these services more efficient and scalable.

“You can have specialty products, but it’s the services that are offered around it that are going to have pull through for that product. It could be your patient support services, your engagement, your benefits investigation process, your hub services, but then how well are your employees trained?” Patel said. “What kind of training program do you have? Do they understand the disease state? Do they understand what the patient is going though? Additionally, you also have the technology that’s layered into it.”

While the price tag for traditional specialty products continues to surge, with an average annual wholesale acquisition cost (WAC) of $75,000, "specialty-lite" products carry a much lower price point.

Specialty lite is generally defined by WAC, which is typically within the guardrails of $400 to $800 per month, as well as service-level requirements. The categories in which the lite model is emerging are traditionally nonadherent and clinically complex populations whose medications fall within the "specialty-lite" cost guardrails, such as dermatologic conditions ($658.97 average WAC cost for branded products), respiratory conditions ($355.21), ophthalmology ($272), cardiovascular disease ($652.59), and neurological conditions ($495.07).

Although cost may be key in defining the "specialty-lite" model, it is the services that surround it that truly show the potential to improve patient care.

“When we look at the traditional model, the patient walks into the doctor’s office [and] the doctor prescribes the medication, sends it to a retail pharmacy, and the retail pharmacy gets it and processes it. If I’m a retail pharmacist, I’m going to process that prescription, but if I run into a block where I have prior authorization [PA] or anything, I’m not pursuing my PA, especially at a retail pharmacy where I’m doing 700-plus scripts per day. I’m going to call that doctor and say, ‘Hey Doc, I’d rather switch this to another medication that’s covered.’ So, what is happening is the patient isn’t getting the medication the doctor intended to prescribe.”

In the "specialty-lite" fulfillment model, benefits investigation, assistance with PA, patient engagement services, and a co-pay support program keeps patients well informed and helps them obtain the best price for their medication, according to the speakers.

Lanzone noted that the "specialty-lite" model has proven to be effective in improving fulfillment as well as patient adherence rates, but it goes much further than that.

“This is not just an adherence program. There are a lot of adherence programs out there and a lot of very good ones,” he said. “This is a comprehensive pull through program as part of an overall access and distribution strategy.” 

The "specialty-lite" platform leverages the current infrastructure of specialty pharmacies with efficient services and emerging technological solutions that focus on ensuring prescription fulfillment with economic feasibility.

Specialty Lite Model Goes Beyond Improving Adherence

	With drug pricing increasingly becoming a hot button issue and greater consternation surrounding the cost of treating a chronic disease among the general public, it is clear that the health care industry is at a crossroads.

	During the featured session at Asembia’s Specialty Pharmacy Summit 2019, “Specialty Industry Outlook: What’s Next,” speakers Adam Fein, PhD, CEO of the Drug Channels Institute; Lisa Gill, managing director of J.P. Morgan Securities; and Doug Long, vice president of industry relations at IQVIA, explored the radical changes that could be on the horizon from potential legislation that would dramatically alter the health care industry.

	Fein pointed to a proposal from the Department of Health and Human Services that would remove safe harbor protection under the Anti-Kickback Statute for rebates on prescription drugs paid by manufacturers to pharmacy benefit managers (PBMs), Part D plans, and Medicaid managed care organizations.

	“We are at an inflection point that potentially is going to change the entire commercial model of the pharmaceutical industry for the first time in probably a generation,” Fein said. “We are at a turning point that three years ago I didn’t even think was possible. We are potentially on the verge of moving to a world without PBM rebates, a total change in all the ways that we do business.”

	Fein noted a number of factors that have contributed to what would be a dramatic shift in the way that health care is funded, which began to gain steam following a price hike for the epinephrine autoinjector Epipen, which garnered scrutiny in the media and from legislators. He said that the gross-to-net bubble—a term developed by the Drug Channels Institute to describe the profit between the list price a manufacturer sets for a drug and the net price after rebates and other reductions&mdash;has continued to inflate and has driven a multitude of problems with the US drug pricing system.

	“What happened is we have this giant gap between the list, or gross price, and the actual price that is received by the manufacturer,” Fein said. “Some categories are so broken that the gap between the list and the net is 80% or 90%. The net price received by manufacturers is growing in low single digits.”

	The inflation of this bubble has led to three elements that are creating a growing crisis for patients, according to Fein.

	The first element is that the amount in spending either on coinsurance or a deductible is now more than 50% of the total that patients pay out-of-pocket, compared with 15% to 20% a decade ago, according to Fein.

	“Patients can be in the deductible and not be able to afford their insulin because they have to pay the full price,” he said. “That is a travesty and it’s been a travesty of benefit design where we’ve shifted cost to people who maybe don’t need motivation to have skin in the game. If you have cancer, you don’t need motivation to take your medicine. Making it essentially unaffordable through benefit design is, I think, cruel. It doesn’t make any sense to me.”

	The second element is a factor Fein called reverse insurance, which runs counter to normal insurance in which the healthy pay premiums for services they may not need to subsidize the sick.

	“What’s happening now with the gross-to-net bubble is the reverse of that,” he said. “If you are chronically ill, if you have a serious condition that’s generated a lot of rebate dollars, you may be forced to pay a very high price for that drug. The money that you’re contributing is used to lower the premiums of the healthier people.”

	The third element is what Fein called warped incentives, in which all parties in the health care system want list prices to go higher.

	Despite the speculation that has surrounded the rebate rule, during her presentation, Gill said Wall Street does not expect major changes in the short term.

	“We’ll probably have some types of programs that will happen,” she said. “I agree that the world will change, but I really do believe there’s still a great opportunity for the PBM industry to help to manage this.” 

	Gill said that the real value of PBMs is to drive patients to the right drug, which the government has started to appreciate.

	“I do think that PBMs have a real place in the marketplace to drive clinical protocols and to drive clinical outcomes,” she said. “Even if we don’t have rebates, I still think at the end of the day, you’re going to need someone to negotiate based on the size and scale of the marketplace.”

	She added that the persistent challenges in the current health care model have created a situation in which the consumer is becoming the biggest disruptor in health care.

	“Plan design has not been put in place with the thought around how does this impact somebody’s out of pocket costs and those patients now are getting more involved in their health care decisions,” she said. “They are making more of those decisions because they’re paying more out of pocket dollars.”

	Gill said that convenience, quality, and cost will be the key drivers of this disruption, as she warned that a shift to value-based care must come to fruition and that the companies that are part of the solution to this shift will reap the greatest long-term benefits.

	“I had a great conversation with a health care leader last week where he said to me ‘Lisa, we’re going to have Medicare for all 10 years from now if we do not move our health care system toward value-based care’” she said. “The perverse incentives of the way our health care system works today will not last.”

	During his portion of the presentation, Long provided an overview of trends and an outlook for the future of the US pharmaceutical market. He outlined the major forces that are combining to drive the desire for change in the health care system.

	These forces include the increasing cost for care and the growing scrutiny surrounding value, which have prompted a reassessment of the payer role and new sustainable models as patients become more involved in health care decision-making due to the challenges created for the entire system from lack of adherence.

	“During the deductible period, the patient is more likely to abandon their medication,” Long said. “Twenty-seven percent of the time, they will abandon a specialty drug during the deductible period. That’s why copay cards are so important. People are going to say it’s just not worth it to me to take my medication.”

	With a clear need for changes to the health care system to protect patients, the panelists agreed that the current model is reaching a tipping point that could lead to a tectonic shift in care management.

	“This is probably a time of greater change than I’ve ever seen in this industry,” Fein said. “My final piece of advice to you with all this change, with all this trouble, with all this complexity, is please try to stay positive and, as always, test negative.”

During the featured session at Asembiaâ€™s Specialty Pharmacy Summit 2019, â€œSpecialty Industry Outlook: Whatâ€™s Next,â€ speakers Adam Fein, PhD, CEO of the Drug Channels Institute; Lisa Gill, managing director of J.P. Morgan Securities; and Doug Long, vice president of industry relations at IQVIA, explored the radical changes that could be on the horizon from potential legislation that would dramatically alter the health care industry.