Safe Biologics

The U.S. Food and Drug Administration today approved Zarxio (filgrastim-sndz), the first biosimilar product approved in the United States.
Biological products are generally derived from a living organism. They can come from many sources, including humans, animals, microorganisms or yeast.

A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Sandoz, Inc.’s Zarxio is biosimilar to Amgen Inc.’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is approved for the same indications as Neupogen, and can be prescribed by a health care professional for:

• patients with cancer receiving myelosuppressive chemotherapy;
• patients with acute myeloid leukemia receiving induction or consolidation chemotherapy;
• patients with cancer undergoing bone marrow transplantation;
• patients undergoing autologous peripheral blood progenitor cell collection and therapy; and
• patients with severe chronic neutropenia.

“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, M.D. “Patients and the health care community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy and quality standards.”
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, called the “reference product.” This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

The FDA’s approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen. Zarxio has been approved as biosimilar, not as an interchangeable product. Under the BPCI Act, a biological product that that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

The most common expected side effects of Zarxio are aching in the bones or muscles and redness, swelling or itching at injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome, a lung disease that can cause shortness of breath, difficulty breathing or increase the rate of breathing.

For this approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name for this product should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products. While the FDA has not yet issued draft guidance on how current and future biological products marketed in the United States should be named, the agency intends to do so in the near future.

Sandoz, a Novartis company, is based in Princeton, New Jersey. Neupogen is marketed by Amgen, based in San Diego, California.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

The U.S. Food and Drug Administration today approved Zarxio (filgrastim-sndz), the first biosimilar product approved in the United States.
Biological products are generally derived from a living organism. They can come from many sources, including humans, animals, microorganisms or yeast.

A biosimilar product is a biological product that is approved based on a showing that it is highly similar to an already-approved biological product, known as a reference product. The biosimilar also must show it has no clinically meaningful differences in terms of safety and effectiveness from the reference product. Only minor differences in clinically inactive components are allowable in biosimilar products.

Sandoz, Inc.’s Zarxio is biosimilar to Amgen Inc.’s Neupogen (filgrastim), which was originally licensed in 1991. Zarxio is approved for the same indications as Neupogen, and can be prescribed by a health care professional for:

• patients with cancer receiving myelosuppressive chemotherapy;
• patients with acute myeloid leukemia receiving induction or consolidation chemotherapy;
• patients with cancer undergoing bone marrow transplantation;
• patients undergoing autologous peripheral blood progenitor cell collection and therapy; and
• patients with severe chronic neutropenia.

“Biosimilars will provide access to important therapies for patients who need them,” said FDA Commissioner Margaret A. Hamburg, M.D. “Patients and the health care community can be confident that biosimilar products approved by the FDA meet the agency’s rigorous safety, efficacy and quality standards.”
The Biologics Price Competition and Innovation Act of 2009 (BPCI Act) was passed as part of the Affordable Care Act that President Obama signed into law in March 2010. The BPCI Act created an abbreviated licensure pathway for biological products shown to be “biosimilar” to or “interchangeable” with an FDA-licensed biological product, called the “reference product.” This abbreviated licensure pathway under section 351(k) of the Public Health Service Act permits reliance on certain existing scientific knowledge about the safety and effectiveness of the reference product, and enables a biosimilar biological product to be licensed based on less than a full complement of product-specific preclinical and clinical data.

A biosimilar product can only be approved by the FDA if it has the same mechanism(s) of action, route(s) of administration, dosage form(s) and strength(s) as the reference product, and only for the indication(s) and condition(s) of use that have been approved for the reference product. The facilities where biosimilars are manufactured must also meet the FDA’s standards.

The FDA’s approval of Zarxio is based on review of evidence that included structural and functional characterization, animal study data, human pharmacokinetic and pharmacodynamics data, clinical immunogenicity data and other clinical safety and effectiveness data that demonstrates Zarxio is biosimilar to Neupogen. Zarxio has been approved as biosimilar, not as an interchangeable product. Under the BPCI Act, a biological product that that has been approved as an “interchangeable” may be substituted for the reference product without the intervention of the health care provider who prescribed the reference product.

The most common expected side effects of Zarxio are aching in the bones or muscles and redness, swelling or itching at injection site. Serious side effects may include spleen rupture; serious allergic reactions that may cause rash, shortness of breath, wheezing and/or swelling around the mouth and eyes; fast pulse and sweating; and acute respiratory distress syndrome, a lung disease that can cause shortness of breath, difficulty breathing or increase the rate of breathing.

For this approval, the FDA has designated a placeholder nonproprietary name for this product as “filgrastim-sndz.” The provision of a placeholder nonproprietary name for this product should not be viewed as reflective of the agency’s decision on a comprehensive naming policy for biosimilar and other biological products. While the FDA has not yet issued draft guidance on how current and future biological products marketed in the United States should be named, the agency intends to do so in the near future.

Sandoz, a Novartis company, is based in Princeton, New Jersey. Neupogen is marketed by Amgen, based in San Diego, California.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Measure would require pharmacists to inform doctors when they use new drugs, as well as generic ‘biosimilars’

Andrew Kitchenman

In recent years, many of the bestselling new medications haven’t been traditional drugs chemically synthesized in labs. Instead, they belong to a growing class of “biologics” — substances that are cultivated from living cells, often by altering the DNA that carries genetic information.

Biologics have been a boon to those with a variety of conditions, and are widely used to treat rheumatoid arthritis as well as to fight infections in chemotherapy patients. But these products often are expensive to develop and buy, racking up $66.3 billion in sales nationally in 2013. That’s why the 2010 Affordable Care Act included a provision to encourage the development of generic products that would be similar to but cheaper than the name-brand biologics.

New Jersey laws don’t cover how these so-called biosimilars should prescribed, which is why the Legislature is grappling with ways to regulate them. Biologics-industry representatives have supported state-level legislation addressing biosimilars prescriptions across the country. In fact, biosimilars aren’t yet available in the United States but could result in significant savings if the federal Food and Drug Administration approves.

Assemblywoman Pamela R. Lampitt (D-Burlington and Camden) noted estimates that biosimilars — which are currently sold in France, Canada, and other countries — could cut the cost of biologics by by 30 percent. That would translate into significant savings to the State Health Benefits Program.

Since state laws governing generic drugs don’t cover biosimilars, which are different from conventional drugs, Lampitt is working on legislation that would determine how pharmacies dispense this emerging class of medications. Without a new law, patients will only be able to receive lower-cost biosimilars if their doctor prescribers a biosimilar instead of a name-brand biologic.

Similar legislative efforts are ongoing in state legislatures across the country, as the FDA moves closer to approving biosimilars.

Lampitt noted that prescriptions for biologics should be treated differently than for traditional drugs, citing concerns over how subtle differences between name-brand biologics and biosimilars — and even between different batches of the same biologic — will affect patients.

She wants to require pharmacies to notify doctors every time they fill a prescription for a biologic, giving them a chance to respond if they have concerns about how the prescriptions are being filled.

Dr. Thomas Felix, research and development policy director for California-based Amgen, said his company is developing nine different biosimilars designed to compete with brand-name biologics whose patent protection is ending.

He said state-level legislation would ensure that doctors receive more information about biologic prescriptions than they currently do for traditional kinds of generic drugs.

Lampitt is working to revise the original version of a bill, A-2477 /S-1705, which currently would require pharmacists to directly inform patients when they substitute a biosimilar for a name-brand biologic. It’s expected to be amended so that the pharmacists would only have to notify doctors. Pharmacists would be required to notify doctors about all biologic prescriptions, not just when pharmacists substitute biosimilars.

John Holub, executive director of pharmacy trade group the New Jersey Council of Chain Drug Stores, said the industry would prefer that any new requirements for pharmacies be based on specific requests from doctors.

“This bill definitely deviates from the time-tested substitution laws,” Holub said, adding that the state could simply change current laws governing generic drugs to include biosimilars.

Holub also questioned the timing of the bill, saying that the FDA hasn’t even laid out its plans for how biosimilars will be regulated.

Sarah M. Adelman, vice president of insurance industry group the New Jersey Association of Health Plans, said insurers want to ensure that biosimilars are treated fairly and that patients aren’t wrongly led to fear that they are inferior to name-brand biologics.

The bill “should not limit, narrow or thwart the use of biosimilars in New Jersey by requiring notification; consent; reporting; or unnecessary barriers to access,” said Adelman.

Providing doctors with more information about biologics prescriptions drew support from groups that advocate for research and treatment of specific diseases.

Ethan Hasbrouck of the American Cancer Society Cancer Action Network said sharing more information with doctors about how prescriptions are filled would ensure that they have accurate records and contribute to patient safety.

“We’re very supportive of the advancement of both biologics and biosimilars because of their enormous potential as an effective tool in the fight against cancer and improving the quality of life of those cancer patients,” he said.

East Brunswick resident Christine Citera, who has psoriatic arthritis, said biologic medication has been essential in improving her quality of life.

“I’ve maintained my full-time job, I’ve hiked, I’ve gotten married — I was able to dance at my wedding,” she said. “Last year, I didn’t think that that was possible, and the biologic medication really allowed me to do this.”

But she said she’s had difficulty getting prescriptions filled and said it would be helpful to have legislation that made it clear what the responsibility of pharmacies are regarding biologics.

 

Measure would require pharmacists to inform doctors when they use new drugs, as well as generic ‘biosimilars’

Andrew Kitchenman

In recent years, many of the bestselling new medications haven’t been traditional drugs chemically synthesized in labs. Instead, they belong to a growing class of “biologics” — substances that are cultivated from living cells, often by altering the DNA that carries genetic information.

Biologics have been a boon to those with a variety of conditions, and are widely used to treat rheumatoid arthritis as well as to fight infections in chemotherapy patients. But these products often are expensive to develop and buy, racking up $66.3 billion in sales nationally in 2013. That’s why the 2010 Affordable Care Act included a provision to encourage the development of generic products that would be similar to but cheaper than the name-brand biologics.

New Jersey laws don’t cover how these so-called biosimilars should prescribed, which is why the Legislature is grappling with ways to regulate them. Biologics-industry representatives have supported state-level legislation addressing biosimilars prescriptions across the country. In fact, biosimilars aren’t yet available in the United States but could result in significant savings if the federal Food and Drug Administration approves.

Assemblywoman Pamela R. Lampitt (D-Burlington and Camden) noted estimates that biosimilars — which are currently sold in France, Canada, and other countries — could cut the cost of biologics by by 30 percent. That would translate into significant savings to the State Health Benefits Program.

Since state laws governing generic drugs don’t cover biosimilars, which are different from conventional drugs, Lampitt is working on legislation that would determine how pharmacies dispense this emerging class of medications. Without a new law, patients will only be able to receive lower-cost biosimilars if their doctor prescribers a biosimilar instead of a name-brand biologic.

Similar legislative efforts are ongoing in state legislatures across the country, as the FDA moves closer to approving biosimilars.

Lampitt noted that prescriptions for biologics should be treated differently than for traditional drugs, citing concerns over how subtle differences between name-brand biologics and biosimilars — and even between different batches of the same biologic — will affect patients.

She wants to require pharmacies to notify doctors every time they fill a prescription for a biologic, giving them a chance to respond if they have concerns about how the prescriptions are being filled.

Dr. Thomas Felix, research and development policy director for California-based Amgen, said his company is developing nine different biosimilars designed to compete with brand-name biologics whose patent protection is ending.

He said state-level legislation would ensure that doctors receive more information about biologic prescriptions than they currently do for traditional kinds of generic drugs.

Lampitt is working to revise the original version of a bill, A-2477 /S-1705, which currently would require pharmacists to directly inform patients when they substitute a biosimilar for a name-brand biologic. It’s expected to be amended so that the pharmacists would only have to notify doctors. Pharmacists would be required to notify doctors about all biologic prescriptions, not just when pharmacists substitute biosimilars.

John Holub, executive director of pharmacy trade group the New Jersey Council of Chain Drug Stores, said the industry would prefer that any new requirements for pharmacies be based on specific requests from doctors.

“This bill definitely deviates from the time-tested substitution laws,” Holub said, adding that the state could simply change current laws governing generic drugs to include biosimilars.

Holub also questioned the timing of the bill, saying that the FDA hasn’t even laid out its plans for how biosimilars will be regulated.

Sarah M. Adelman, vice president of insurance industry group the New Jersey Association of Health Plans, said insurers want to ensure that biosimilars are treated fairly and that patients aren’t wrongly led to fear that they are inferior to name-brand biologics.

The bill “should not limit, narrow or thwart the use of biosimilars in New Jersey by requiring notification; consent; reporting; or unnecessary barriers to access,” said Adelman.

Providing doctors with more information about biologics prescriptions drew support from groups that advocate for research and treatment of specific diseases.

Ethan Hasbrouck of the American Cancer Society Cancer Action Network said sharing more information with doctors about how prescriptions are filled would ensure that they have accurate records and contribute to patient safety.

“We’re very supportive of the advancement of both biologics and biosimilars because of their enormous potential as an effective tool in the fight against cancer and improving the quality of life of those cancer patients,” he said.

East Brunswick resident Christine Citera, who has psoriatic arthritis, said biologic medication has been essential in improving her quality of life.

“I’ve maintained my full-time job, I’ve hiked, I’ve gotten married — I was able to dance at my wedding,” she said. “Last year, I didn’t think that that was possible, and the biologic medication really allowed me to do this.”

But she said she’s had difficulty getting prescriptions filled and said it would be helpful to have legislation that made it clear what the responsibility of pharmacies are regarding biologics.