Feature

Gottlieb resignation raises questions about the future of biosimilars in the US

Scott Gottlieb
Scott Gottlieb

When Scott Gottlieb, MD, announced on March 5 that he would be resigning as Commissioner of the FDA, a ripple went through the health care regulation community about the future of many of his signature initiatives, including the Medical Device Safety Action Plan, the Biosimilars Action Plan, and the Drug Competition Action Plan.

Clinicians in a number of health care specialties, including rheumatology and oncology, are looking with particular interest at the biosimilar initiative, and how incoming acting FDA Commissioner Norman E. “Ned” Sharpless, MD, director of the National Cancer Institute, will handle these drugs when he takes over on April 5. As with almost every aspect of the biosimilar phenomenon in the U.S., the future for biosimilars under Sharpless’ direction after the rash of approvals under Gottlieb’s stint over the past 2 years remains unpredictable.

Looking forward first, in a recent conversation at the Hutchins Center on Fiscal & Monetary Policy and the USC-Brookings Schaeffer Initiative for Health Policy at Brookings, Gottlieb outlined some the challenges to an increased role of biosimilars in the market in the coming years. “I would point first and foremost to some of the commercial obstacles to biosimilars and the fact that the incumbent biologics have large royalties associated with them,” he said. “The manufacturers are smart — they amp up the royalties on the eve of a biosimilar entry [into the market].”

He went on to say that if a health plan is to adopt the biosimilar onto their formulary, they stand to lose the rebates associated with the bio-originator. “In order to offset the rebates, you have to move enough market share to the biosimilar to take advantage of the discount, but that’s hard to do in this market because the plans seem to have a difficult time converting physicians and patients to the biosimilars,” he said.

Gottlieb cited physician resistance as another key obstacle biosimilars may face moving forward. However, he remains optimistic. “As the market develops, as doctors gain more acceptance and comfort with biosimilars . . . I think this market is going to evolve and be very robust,” he said.

Despite his many efforts at bringing these drugs to patients during his tenure as FDA chief — 15 biosimilars have received FDA approval, including seven in 2018 and two so far in 2019 — Gottlieb is not surprised that, perhaps due to the aforementioned reasons, the biosimilar market has been slow to develop in the U.S. “Some of the early expectations and predictions in 2003 and 2005 were bold,” he said.

That said, there is some consensus that Gottlieb was effective in executing his goals in the biosimilar space.

Effective Leader

Angus Worthing

“The American College of Rheumatology commends Dr. Gottlieb for his agency’s efforts to lower the cost of prescription drugs and bring safe, effective biosimilars to market — a top priority for the rheumatology community,” Angus Worthing, MD, chair of the Government Affairs Committee of the American College of Rheumatology, told Healio Rheumatology in an interview. “His support for the draft pathway for the approval of interchangeable biosimilars has been a crucial step towards increasing patients’ access to affordable biosimilars.”

This sentiment was echoed by Allan Gibofsky, MD, JD, professor of medicine and public health at Weill Medical College of Cornell University and attending rheumatologist at the Hospital for Special Surgery in New York City. “Commissioner Gottlieb was a vocal advocate for the introduction and utilization of biosimilars,” he said in an interview. “His comments reassured clinicians that the Administration would only approve a biosimilar if it met the Administration’s rigorous safety standards already in place for existing biologics.”

Gibofsky believes that the initial concerns of safety and efficacy of biosimilars have largely been addressed. “Further, as some of the litigation between the bio-originator and biosimilar manufacturers has been settled and/or is nearing resolution, this will increase the number of biosimilars in the market, as well,” he said.

Stanford Shoor, MD, clinical professor of medicine at Stanford Health Care, stressed the clinical aspect of bringing biosimilars into the forefront of the clinic in the U.S. “Over the last several years, we have gotten from speculation to utilization,” he told Healio Rheumatology. “We have moved past the point at which we wondered whether they would be successful, or have different toxicities as the bio-originals.”

Perhaps more importantly, the U.S. may finally be catching up to Europe and other parts of the world, where biosimilars are more widely used. However, those who believe that success in Europe would translate immediately into a large market share in the U.S. may have been disappointed, according to Gibofsky. EULAR guidelines state the drugs are equivalent, and should be used because they are more cost-effective. 

“The initial promise of biosimilars was that they would decrease cost and increase patient access,” Gibofsky said “However, it is not clear that the European experience has been extrapolated to the U.S. For one thing, initial price discounts were modest and thus cost savings do not seem to be significant. For another, it was not clear to the treating physician that these acquisition cost savings were realized by the patient, as opposed to bring retained by the insurer.”

The next question that still needs to be debated pertains to the switching capability of these drugs, according to Shoor. “If you switch from, say, Remicade (infliximab, Janssen) to the biosimilar, what percentage of patients are going to fail that switch?” he said. “The controversy is still going on in the literature, and presumably will go on at least into the near future.”

Alan Gibofsky, MD
Allan Gibofsky

All of these factors often leave clinicians stranded at the intersection between market and clinical factors, according to Gibofsky. “Although biosimilars are cheaper for the insurance company to buy, the treating physician has seen no decrease in the sometimes-onerous prior authorization requirements — which I call the “hassle factor” — of a biosimilar, thus providing no incentive to either initiate a biosimilar or switch a stable patient,” he said. “Also, there remains clinical uncertainty about switching stable patients back and forth, not between a bio-originator and a biosimilar, but, rather, between several biosimilars to the same bio-originator.”

Next in Line

With all of these questions still lingering, Sharpless has his work cut out for him. While many experts are loathe to speculate about what his tenure may look like, physicians across specialties appear eager to keep the momentum rolling for biosimilars.

“HHS Secretary Alex Azar has been a vigorous champion for implementing strategies for reducing prescription drug prices,” Gibofsky said. “It is reasonable to assume that acting Commissioner Sharpless is a proponent and has adopted this philosophy as well. Further, as an oncologist, Dr. Sharpless has direct familiarity with the cost of biologic and immunologic therapies and their impact on patients, and thus I would expect he views biosimilars as an effective cost reduction strategy.”

“The ACR looks forward to working closely with Acting FDA Commissioner Ned Sharpless,” Worthing said. “We hope the interchangeable biosimilar pathway will be finalized as drafted, with guidance for 3-switch clinical studies, in due haste under the new commissioner’s leadership. By doing so, we have a historic opportunity to increase competition, lower drug costs, and improve patient access to safe and proven therapies for the millions of Americans living with rheumatic diseases.”

For Shoor, the cost-effectiveness argument may ultimately win out. “The Federal government is among the largest, if not the largest, payor,” he said. “We have to wonder how they will look upon these drugs in the future. My guess is that they will look at them as being more cost-effective, and will continue to support their use.”

This, then, raises the question of whether other payors will follow suit. Shoor was less certain about this. “There is no natural progression if the government adopts a class of drugs that it will end up on formularies in the private sector,” he said. But he looked to the clinical community to be leaders in this regard. “Clinicians and practitioners tend to be early adopters of new practices and therapies.”

But they can only carry the ball so far, according to Shoor. “As much as they would like to adopt new drugs that are shown to be comparably safe and effective as existing therapies, they run into the brick wall of preauthorization,” he said. “If there is no rebate, there is no advantage.”

The key to increased adoption of biosimilars in the U.S., for Shoor, is for both physicians and regulators to view the situation through the eyes of a patient. “You are going to have to potentially pay out $4,000 or $5,000 for this drug, but then someone tells you that you can get a bioequivalent that is 50% less,” he said. “What would you do? The question is a lot simpler for a patient.”

Shoor acknowledged the myriad larger forces at work. However, he offered a solution. “If there are still questions about the real-world efficacy and tolerability of these drugs, what we need to be doing now is post-marketing surveillance,” he said. “We need to determine if there are effects of these drugs outside of the confines of a clinical trial environment.”

Whether acting Commissioner Sharpless will consider these factors or continue the work of Gottlieb in the biosimilar space remains to be seen.  – by Rob Volansky

For more information:

  • Stanford Shoor, MD, can be reached at 900 Blake Wilbur Drive, 2nd Floor, Room W2081, Palo Alto, CA 94304; email: LiKim@stanfordhealthcare.org
  • Allan Gibofsky, MD, JD, can be reached at 523 E 71st St 7th Floor, New York, NY 10021; email: GibofskyA@hss.edu.
  • Angus B. Worthing, MD, can be reached at 2730 University Blvd. West, Suite 310, Wheaton, MD 20902; email: JGivens@rheumatology.org.

Disclosures: Gibofsky reports consulting and speaking for Abbvie, Celgene, Flexion, Merck, Novartis, Pfizer, and Sandoz; consulting for Fortress, Relburn, and Samumed; and being a stockholder for Abbvie, Amgen, J & J, Pfizer, and Regeneron. Shoor and Worthing report no relevant financial disclosures.

Scott Gottlieb
Scott Gottlieb

When Scott Gottlieb, MD, announced on March 5 that he would be resigning as Commissioner of the FDA, a ripple went through the health care regulation community about the future of many of his signature initiatives, including the Medical Device Safety Action Plan, the Biosimilars Action Plan, and the Drug Competition Action Plan.

Clinicians in a number of health care specialties, including rheumatology and oncology, are looking with particular interest at the biosimilar initiative, and how incoming acting FDA Commissioner Norman E. “Ned” Sharpless, MD, director of the National Cancer Institute, will handle these drugs when he takes over on April 5. As with almost every aspect of the biosimilar phenomenon in the U.S., the future for biosimilars under Sharpless’ direction after the rash of approvals under Gottlieb’s stint over the past 2 years remains unpredictable.

Looking forward first, in a recent conversation at the Hutchins Center on Fiscal & Monetary Policy and the USC-Brookings Schaeffer Initiative for Health Policy at Brookings, Gottlieb outlined some the challenges to an increased role of biosimilars in the market in the coming years. “I would point first and foremost to some of the commercial obstacles to biosimilars and the fact that the incumbent biologics have large royalties associated with them,” he said. “The manufacturers are smart — they amp up the royalties on the eve of a biosimilar entry [into the market].”

He went on to say that if a health plan is to adopt the biosimilar onto their formulary, they stand to lose the rebates associated with the bio-originator. “In order to offset the rebates, you have to move enough market share to the biosimilar to take advantage of the discount, but that’s hard to do in this market because the plans seem to have a difficult time converting physicians and patients to the biosimilars,” he said.

Gottlieb cited physician resistance as another key obstacle biosimilars may face moving forward. However, he remains optimistic. “As the market develops, as doctors gain more acceptance and comfort with biosimilars . . . I think this market is going to evolve and be very robust,” he said.

Despite his many efforts at bringing these drugs to patients during his tenure as FDA chief — 15 biosimilars have received FDA approval, including seven in 2018 and two so far in 2019 — Gottlieb is not surprised that, perhaps due to the aforementioned reasons, the biosimilar market has been slow to develop in the U.S. “Some of the early expectations and predictions in 2003 and 2005 were bold,” he said.

That said, there is some consensus that Gottlieb was effective in executing his goals in the biosimilar space.

Effective Leader

Angus Worthing

“The American College of Rheumatology commends Dr. Gottlieb for his agency’s efforts to lower the cost of prescription drugs and bring safe, effective biosimilars to market — a top priority for the rheumatology community,” Angus Worthing, MD, chair of the Government Affairs Committee of the American College of Rheumatology, told Healio Rheumatology in an interview. “His support for the draft pathway for the approval of interchangeable biosimilars has been a crucial step towards increasing patients’ access to affordable biosimilars.”

This sentiment was echoed by Allan Gibofsky, MD, JD, professor of medicine and public health at Weill Medical College of Cornell University and attending rheumatologist at the Hospital for Special Surgery in New York City. “Commissioner Gottlieb was a vocal advocate for the introduction and utilization of biosimilars,” he said in an interview. “His comments reassured clinicians that the Administration would only approve a biosimilar if it met the Administration’s rigorous safety standards already in place for existing biologics.”

Gibofsky believes that the initial concerns of safety and efficacy of biosimilars have largely been addressed. “Further, as some of the litigation between the bio-originator and biosimilar manufacturers has been settled and/or is nearing resolution, this will increase the number of biosimilars in the market, as well,” he said.

Stanford Shoor, MD, clinical professor of medicine at Stanford Health Care, stressed the clinical aspect of bringing biosimilars into the forefront of the clinic in the U.S. “Over the last several years, we have gotten from speculation to utilization,” he told Healio Rheumatology. “We have moved past the point at which we wondered whether they would be successful, or have different toxicities as the bio-originals.”

Perhaps more importantly, the U.S. may finally be catching up to Europe and other parts of the world, where biosimilars are more widely used. However, those who believe that success in Europe would translate immediately into a large market share in the U.S. may have been disappointed, according to Gibofsky. EULAR guidelines state the drugs are equivalent, and should be used because they are more cost-effective. 

“The initial promise of biosimilars was that they would decrease cost and increase patient access,” Gibofsky said “However, it is not clear that the European experience has been extrapolated to the U.S. For one thing, initial price discounts were modest and thus cost savings do not seem to be significant. For another, it was not clear to the treating physician that these acquisition cost savings were realized by the patient, as opposed to bring retained by the insurer.”

PAGE BREAK

The next question that still needs to be debated pertains to the switching capability of these drugs, according to Shoor. “If you switch from, say, Remicade (infliximab, Janssen) to the biosimilar, what percentage of patients are going to fail that switch?” he said. “The controversy is still going on in the literature, and presumably will go on at least into the near future.”

Alan Gibofsky, MD
Allan Gibofsky

All of these factors often leave clinicians stranded at the intersection between market and clinical factors, according to Gibofsky. “Although biosimilars are cheaper for the insurance company to buy, the treating physician has seen no decrease in the sometimes-onerous prior authorization requirements — which I call the “hassle factor” — of a biosimilar, thus providing no incentive to either initiate a biosimilar or switch a stable patient,” he said. “Also, there remains clinical uncertainty about switching stable patients back and forth, not between a bio-originator and a biosimilar, but, rather, between several biosimilars to the same bio-originator.”

Next in Line

With all of these questions still lingering, Sharpless has his work cut out for him. While many experts are loathe to speculate about what his tenure may look like, physicians across specialties appear eager to keep the momentum rolling for biosimilars.

“HHS Secretary Alex Azar has been a vigorous champion for implementing strategies for reducing prescription drug prices,” Gibofsky said. “It is reasonable to assume that acting Commissioner Sharpless is a proponent and has adopted this philosophy as well. Further, as an oncologist, Dr. Sharpless has direct familiarity with the cost of biologic and immunologic therapies and their impact on patients, and thus I would expect he views biosimilars as an effective cost reduction strategy.”

“The ACR looks forward to working closely with Acting FDA Commissioner Ned Sharpless,” Worthing said. “We hope the interchangeable biosimilar pathway will be finalized as drafted, with guidance for 3-switch clinical studies, in due haste under the new commissioner’s leadership. By doing so, we have a historic opportunity to increase competition, lower drug costs, and improve patient access to safe and proven therapies for the millions of Americans living with rheumatic diseases.”

For Shoor, the cost-effectiveness argument may ultimately win out. “The Federal government is among the largest, if not the largest, payor,” he said. “We have to wonder how they will look upon these drugs in the future. My guess is that they will look at them as being more cost-effective, and will continue to support their use.”

This, then, raises the question of whether other payors will follow suit. Shoor was less certain about this. “There is no natural progression if the government adopts a class of drugs that it will end up on formularies in the private sector,” he said. But he looked to the clinical community to be leaders in this regard. “Clinicians and practitioners tend to be early adopters of new practices and therapies.”

But they can only carry the ball so far, according to Shoor. “As much as they would like to adopt new drugs that are shown to be comparably safe and effective as existing therapies, they run into the brick wall of preauthorization,” he said. “If there is no rebate, there is no advantage.”

The key to increased adoption of biosimilars in the U.S., for Shoor, is for both physicians and regulators to view the situation through the eyes of a patient. “You are going to have to potentially pay out $4,000 or $5,000 for this drug, but then someone tells you that you can get a bioequivalent that is 50% less,” he said. “What would you do? The question is a lot simpler for a patient.”

Shoor acknowledged the myriad larger forces at work. However, he offered a solution. “If there are still questions about the real-world efficacy and tolerability of these drugs, what we need to be doing now is post-marketing surveillance,” he said. “We need to determine if there are effects of these drugs outside of the confines of a clinical trial environment.”

Whether acting Commissioner Sharpless will consider these factors or continue the work of Gottlieb in the biosimilar space remains to be seen.  – by Rob Volansky

For more information:

  • Stanford Shoor, MD, can be reached at 900 Blake Wilbur Drive, 2nd Floor, Room W2081, Palo Alto, CA 94304; email: LiKim@stanfordhealthcare.org
  • Allan Gibofsky, MD, JD, can be reached at 523 E 71st St 7th Floor, New York, NY 10021; email: GibofskyA@hss.edu.
  • Angus B. Worthing, MD, can be reached at 2730 University Blvd. West, Suite 310, Wheaton, MD 20902; email: JGivens@rheumatology.org.

Disclosures: Gibofsky reports consulting and speaking for Abbvie, Celgene, Flexion, Merck, Novartis, Pfizer, and Sandoz; consulting for Fortress, Relburn, and Samumed; and being a stockholder for Abbvie, Amgen, J & J, Pfizer, and Regeneron. Shoor and Worthing report no relevant financial disclosures.

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