Biologics and Biosimilars

Question 1

what is a biologic

Answer 1

A medication derived from a living organism or their cells

Larger and more complex then traditional pharmaceutical products

Question 2

How do regulations regarding biologics differ

Answer 2

Biologics differ from other drugs for human use in that they must include more detailed chemistry and manufacturing information compared to other drugs (ensures it isnt contaminated by an undesired microorganism or another biologic)
An inspection of the manufacturing facility, known as an On-Site Evaluation (OSE) is also completed to assess the production process and facility
Biologics are then monitored by being placed on a lot release schedule tailored to their potential risk, manufacturing, testing, and inspection history to date

Question 3

what are some types of biologics?

Answer 3

Blood and blood components 
Proteins 
Human tissues 
Vaccines 
Allergenic extracts 
Cellular and gene therapies

Question 4

when was the first biologic developed?

Answer 4

First biologic (rDNA insulin) in 1982

Question 5

who are the major players in biotech?

Answer 5

• AbbVie
  
  • Gilead
  • Genentech
  • Amgen
  • Bayer

Question 6

where is the biologic space at today?

Answer 6

• May see a boost in those companies invested in COVID-19 Developments
  
  • 5 out of 10 top drugs are in the oncology space
  • Keytruda (pembroluzimab) may hit $26 billion/year by 2025

Question 7

why are biologics so important?

Answer 7

Biologics hold great promise for providing a lower cost treatment option for chronic disease

Question 8

why are biologics so expensive

Answer 8

1. Manufacturing costs
   
   2. Research and development costs
   3. Competition (free market and benchmark pricing)
   4. Many biologics target rare diseases, so the market for them is so small

Question 9

what are intellectual property rights

Answer 9

Period of time following marketing approval during which competing firms may not use the innovative firms clinical trial date in order to obtain marketing authroization for a generic version

Question 10

what are the benefits or intellectual property rights

Answer 10

Data exclusivity grants the innovative firm a period of protection for their investment in clinical trials and data collection
Gives incentives to invest in the difficult and expensive research and development necessary for biologics advances

Question 11

what are some future issues for biologics

Answer 11

• Market exclusivity will erode as patents expire and competing products enter the market
  
  • Revenues generated by biologics are threatened by increasing scrutiny from government health agencies and other payers
  • In CAN, prevalence of off-label use is estimated at 11%, and of off-labels prescriptions, 79% lacked strong scientific evidence

Question 12

what is a biosimilar

Answer 12

A biosimilar is a copy of a commercially available biopharmaceutical (reference product) that no longer is protected by patent which has:
Undergone rigorous analytical and clinical assessment, in comparison to its reference product
AND
Been approved by a regulatory agency according to a specific pathway for biosimilar evaluation

Question 13

why is it called a biosimilar and not a generic?

Answer 13

A biosimilar is “highly similar” to its reference product in physiochemical characteristics, efficacy, and safety
HC approval of a biosimilar is not a declaration of pharmaceutical equivalence, bioequivalence or clinical equivalence to the reference biologic drug
Cannot say they are exact

Question 14

why are biosimilars important?

Answer 14

Additional treatment choices at a lower cost

Increased access to biologics, which may lead to improved health outcomes overall

Question 15

why have biosimilars created a new market?

Answer 15

Bringing a biosimilar to market will be more costly and less certain than producing a generic drug
Wont see anymore than 3-4 biosimilars come on the market, shares the wealth but doesn’t dilute the market so much that it reduces the drug cost too far

Question 16

To have a biosimilar approved do you have to prove bioequivalence?

Answer 16

NO

Must conduct at least 1 clinical trial for toxicity, immunogenicity, PK, and analytical studies

Question 17

what does it mean by saying biosimilars are “highly similar” to biologics

Answer 17

Minor differences between the references product and the proposed biosimilar product in clinically inactive components are acceptable

Question 18

what are the regulations regarding biosimilar approval?

Answer 18

Although submission is rigorous and based on RCTs, a reduced non-clinical and clinical package vs. the innovator
The dosage forms, strengths, and routes of administration of the biosimilar should be the same as that of the reference biologic Post-marketing safety programs (Phase 4: real-world effectiveness) must also be in place
Authorization of a biosimilar is not a declaration of interchangeability nor substitutability

Question 19

who determines if biosimilars and biologics are interchangeable?

Answer 19

It’s the provinces who decide if the biosimilar and innovator may be interchangeable

Question 20

can information about biosimilars be extrapolated to other indications where clinical studies HAVE NOT been done?

Answer 20

YES, Clinical studies don’t need to be performed for each indication

Question 21

what is switching?

Answer 21

Switching refers to a one-time change from a reference biologic drug to a biosimilar
Health CAN recommends that a decision to switch a patient being treated with a reference biologic drug to a biosimilar should be made by the treating physician in consultation with the patients and taking into account available clinical evidence and any policies of the relevant jurisdiction

Question 22

What are Pros for switching

Answer 22

Efficacy and safety data generally showed no differences between patients who switched treatments vs. those who did no
Switching doesn’t appear to be associate with any major efficacy, safety, or immunogenicity issues

Question 23

what are Cons for switching

Answer 23

Immunogenicity: Biologics injected into the body: the immune system will often react
To be approved, biosimilars must show no clinically meaningful differences in immunogenicity, and it must be monitored after approval however, immunogenicity can range from not-clinically significant to eliciting an immune response which can effect safety and efficacy

some physicians feel switching isnt in their patients best interest

Question 24

what is the overall verdict on switching

Answer 24

• For treatment naïve patients, its generally supported that one can start on a biosimilar
  
  • For non-naïve patients, most regulatory bodies have said switching to a biosimilar can be done safely
  • Some physicians and patients arent in favor of non-medical switching
  • Will better know the long-term impact in a few years time with more research and experience

Question 25

what are the challenges for public payers surrounding biosimilars

Answer 25

Biosimilar market dynamics are different than oral generics
Health CAN approves these, currently no interchangeability framework
Biosimilar manufacturers: less experienced and fragmented (generic and brand players)
Must listen to desires of prescribers and patients
Patient indications
Infusion costs/infrastructure

Question 26

what are patient perceptions on biosimilars?

Answer 26

75-80% believed biosimilars are different and will have different adverse events than the originator
80% say you shouldn’t recommend switching
Healthcare providers were least frequent source of information

Question 27

what are physician perspectives on biosimilars

Answer 27

45% felt them to be safe and appropriate (despite the fact that most trust the FDA approval process)
Physician experience and comfort with brand
Patient outcomes is of prime importance
Concerns for biosimilars vary by therapeutic area
Manufacturer experience with biologic production is meaningful

Question 28

how will pharmacists be involved in the switching to biosimilars?

Answer 28

Communication with prescribers
Informing the patient what a biosimilar is
Pharmacists have a responsibility to inform patients about available treatment options, including lower-cost alternatives such as biosimilars
Close relationships with prescribers will be important
Pharmacists should report Aes