Safe Biologics

On August 28th, the Journal of the Generics and Biosimilars Initiative (GaBI Journal) published a whitepaper entitled “European prescribers’ attitudes and beliefs on biologicals prescribing and automatic substitution”. The paper explores in detail the findings of ASBM’s survey of 579 prescribers of biologic medicines from 10 practice areas in 6 Western European countries.

Topics examined include physician perspectives on prescribing biosimilars, physician-led biosimilar substitution vs. third-party substitution, adverse event reporting, and design of government tenders.

As detailed in the paper, European physicians have increased their familiarity with biosimilars since last surveyed in 2013, but as their familarity increased, so too has the importance to them of maintaining control of treatment decisions:

• 82% consider maintaining physician control of treatment decisions to be very important or critical, representing a 10% increase from the 2013 survey.
• Physicians are also highly uncomfortable with a non-medical substitution initiated by a third party. This figure too has increased sharply since the 2013 survey: 73% are uncomfortable with this, compared to 58% in 2013.
• A strong majority (63%) consider it highly important for governments to make multiple therapeutic choices available in tenders, and a very strong majority (83%) believe these tenders should take into account factors besides price.

The paper will be also published in Issue 3 of the GabI Journal’s 2020 print edition this fall. 
Read the full whitepaper online here.

The uptake of infliximab biosimilars in the United States is slow but tracks closely to the experience in Europe, according to a new study. After 2 years, infliximab biosimilars assumed a large share of the Europe market. While biosimilar filgrastim has gained large market share in the U.S., uptake of biosimilar infliximab has lagged that of biosimilar filgrastim.

As the Center for Biosimilars reported August 5th:

The study authors said the reasons for the slower adoption of infliximab biosimilars compared with the previous filgrastim biosimilar are unknown. However, they speculated that ‘patients and physicians may be more reluctant to switch from a working biologic regimen in a chronic setting than an acute one.

However, they acknowledged that “a considerable minority of patients did switch between biologic and biosimilar versions in 2018,” and suggested switching could have been the result of cost reductions, such as lower patient co-pays or physician rebates.

Read more about the study here.

The month of August saw two new biosimilars launch in Canada:

The first, Ziextenzo, is a biosimilar pegfilgrastim- a long-acting form of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF), or filgrastim. It is was approved April 21st of this year by Health Canada to decrease the incidence of infection, as manifested by febrile neutropenia, in patients with non-myeloid malignancies receiving myelosuppressive antineoplastic agents. Neutropenia is one of the most serious side effects of chemotherapy.

The second, Riximyo, is a biosimilar to rituximab, a monoclonal antibody approved for the treatment of non-Hodgkin’s lymphoma (NHL) and chronic lymphocytic leukemia (CLL), as well as the rheumatoid arthritis (RA). It was approved by Health Canada on April 28th of this year.

Read more about the approvals here. 

On July 30th, ASBM submitted comments on the National Institute for Occupational Safety and Health’s (NIOSH’s) proposed Hazardous Drugs List additions for 2020. (The original due date for comments had been June 30th, but the comment period was extended to July 30th.)

When the comment period was initially announced, several biologic medicines had been proposed- in ASBM’s view inappropriately- for inclusion on the 2020 NIOSH Proposed List of Hazardous Drugs in Healthcare Settings. These included the biologics trastuzumab and bevacizumab, widely used in cancer treatment.

Thankfully, when extending the deadline for comments, NIOSH indicated that trastuzumab and bevacizumab were no longer being considered for inclusion on the List.

ASBM’s previous comments regarding the inclusion of monoclonal antibodies on the NIOSH list were among those cited in the Federal Register as the reason for the change:

Comment: Monoclonal antibodies (i.e., therapeutic proteins) are of such a large molecular weight that they do not pose a realistic risk to healthcare workers. For example, monoclonal antibodies ‘‘are too large to be absorbed through skin contact, and if ingested, they would be destroyed by digestion; if inhaled, the pulmonary system would prevent absorption. Consequently, these drugs are all administered by injection. The only potential risk to healthcare workers is of an accidental needle stick, which would not inject a pharmacologically active dose.’’

Accordingly, the monoclonal antibodies bevacizumab, blintumomab, and trastuzumab should not be placed on the List, and pertuzumab should be removed from [Table 1].

In ASBM’s comments, executive director Michael Reilly and Philip Schneider commended NIOSH for these revisions to the list:

The placement of these medicines on the NIOSH List would have compelled healthcare workers to take extraordinary precautions when handling and dispensing these drugs- including stringent facility, personal protective equipment, training, and waste disposal requirements specified in standards such as USP chapter <800>.

This would have imposed a significant burden on health care providers, imposing requirements for safe receipt, storage, preparation, and administration. These burdens would have increased health care costs unnecessarily and negatively affected access to these new, breakthrough therapies; such as by limiting which sites these critical medications are available and can be administered, such as infusion clinics and a physician’s office setting.

ASBM recognizes that balancing health care worker safety against health care cost impact and patient access is a complicated consideration in policy development, and we trust that NIOSH will continue to make good decisions as it attempts to strike the proper balance during its deliberations.

More information about the Proposed List of Hazardous Drugs may be found here. 

Read ASBM’s full comments here. 

Biosimilar Working Group Sends Letter to Quebec Health Minister, Urging Rejection of Forced-Substitution Policies

In a letter dated July 29th, the Canada-based Biosimilars Working Group (of which ASBM is a member) urged Quebec Health Minister Christian Dubé, MLA to reject forced biosimilar substitution policies embraced by some Canadian provinces. The group also asked Minister Dubé to gather input from the patient community before adopting a biosimilar substitution policy. From the letter:

In your upcoming deliberations, we request full consultations with patient groups before you reach any conclusions. This way, policy can be forged in a manner that keeps Canadians safe, especially during this current pandemic and beyond. There can be no one-size-fits-all approach and developing policy with fulsome input from those who will be directly impacted will help achieve the desired outcomes effectively.

We thank you for the recent report from INESSS, which concluded that there are certain populations who are taking biologics for which very little or no data are available regarding the safety of switching to biosimilars, and identifies significant concerns that clinicians have about non-medical switching. As patient groups, we share their concerns.

Read the full letter here. 

Report: Canada’s Pharmaceutical Pricing Reforms Creating Negative Impacts for Patients

A sweeping and controversial reform of Canada’s 30-year old regime overseeing patented medicine prices is already creating negative impacts in the life sciences sector and reducing patients’ access to medicines, according to a new report from Innovative Medicines Canada and Life Sciences Ontario.

The regulations, drafted by Canada’s Patented Medicine Prices Review Board (PMPRB) were published in Canada Gazette2 (CG2) in August 2019, signs of its negative impact are already becoming apparent. Among its findings:

• Many therapeutic areas will be impacted by the new PMPRB regulations: These include oncology, biologics, rare disorders, immunology, gene/cell therapy, rheumatology, and other areas; according to a survey of pharmaceutical executives.
• New drug submissions are down: In the 9 months following CG2, there was a decline in timely submissions made in Canada to 24% of global submissions, compared to 35-40% in the 3 previous 12-month periods.
• New drug launches are increasingly delayed: In the 9 months following CG2, delayed or cancelled launches doubled to 42% of approvals, compared to the 3 previous 12-month periods.
• Clinical drug trials are down: As of early June 2020, Informa data suggest that there was a decline in the share of global industry-funded clinical trials that were started in Canada in the 9 months following CG2 down to 9.2% from 10.5% in the 3 previous 12-month periods.
• Patient advocacy organizations are opposed to the PMPRB changes: representatives from the 30-group Best Medicines Coalition, the CF Treatment Society, the Sickle Cell Disease Association, and others have registered their strong opposition to the changes. According to the Canadian Organization for Rare Disorders:

“The Canadian government and particularly Health Canada have completely forgotten about the people it should be serving and helping: Canadian patients. There will be delayed access or, worse, no access to new medicines as a result of these changes, and this will harm patients.”

The report combines data from an opinion survey of pharmaceutical manufacturers with objective metrics on clinical trials, new drug submissions and launches obtained from publicly-available government and commercial databases such as Informa Citeline, Health Canada’s NOC, Drug Product and Drug and Health Product Submissions Under Review databases, and EMA and FDA databases.

Read the full report here. 

FDA Approves 28th Biosimilar, Sixth for Adalimumab

GaBI Journal: UK Study Shows Need for Improved Identification of Biologics

An article in the summer issue of the Journal of the Generics and BIosimilars Initiative (GaBI Journal) emphasizes the need for improved pharmacovigilance with biologic medicines in the UK.

The article, entitled “Poor traceability of biologicals in UK ADR reporting indicates the need for improvements to ensure patient safety” covers the UK BIO-TRAC study, which conducted an online survey of hospital pharmacists and analysed total of 6,108 electronic Adverse Drug Reaction (ADR) reports in order to assess the effectiveness of pharmacovigilance legislation enacted in 2012 to strengthen product identification. As the study authors explain,
Due to their complex structures and the inherent challenges for manufacturing, a degree of minor variability may exist between different batches of the same product and between original biological and follow-on versions, so-called biosimilars. Thus, when adverse drug reactions (ADRs) occur, it is important to know the precise brand name and batch number of the biological involved.

Several studies have concluded, however, that specific product details are not always provided in ADR reports. Consequently, the aim of this study (UK BIO-TRAC study) was to assess the extent to which biologicals are traceable by brand name and batch number in UK hospital practice and in reports of ADRs submitted by patients and healthcare professionals.

The study revealed that brand name recording in routine hospital processes ranged from 79% to 91%, whereas batch numbers were less routinely recorded, ranging from 38% to 58%. Among the ADR reports analyzed, only 38% had an identifiable brand name and 15%, batch numbers. (Note: this is consistent with ASBM’s 2019 survey of UK physicians, which revealed that only 30% consistently include the batch number in ADR reports and 18% rarely or never include them.) 

As the authors conclude, “Whereas batch number traceability in electronic ADR reports improved slightly after the implementation of the European Union pharmacovigilance legislation in 2012, no improvement of brand name traceability was observed in the UK.”

Yet as ASBM noted in its April 2020 presentation at the World Health Organization’s 70th Consultation on International Nonproprietary Names, fully 35% of adverse event reports submitted in the EU for infliximab products in 2018 did not specify a brand name, according to EudraVigilance, the EMA’s database of suspected adverse drug reaction reports.

In order to ensure the accurate identification of all biologic medicines, in 2014 the INN Expert Group recommended the WHO implement the Biologic Qualifier (BQ) proposal – a voluntary standard which affixes distinct four-letter suffixes to the names of biologics which share a nonproprietary name. Despite early support from many countries including the U.S., Canada, Australia, Japan, and others the BQ proposal remains unimplemented. The FDA has since adopted its own BQ-like suffix system.

The article appears in GaBI Journal Volume 9, Year 2020, Issue 2, and may also be read online here.

Read the abstract of the UK BIO-TRAC study here.

Learn more about ASBM’s work to advance the distinct naming of biologics globally here.

Alberta’s Shadow Health Minister, Matt Jeneroux, has used a recent implementation delay for new drug pricing guidelines from the Patented Medicines Pricing Review Board (PMPRB) to collect additional feedback about the proposed changes and will be presenting a comprehensive report to the government in the fall based on his findings.

DIA Annual Canadian Meeting

Virtual – October 19-20, 2020

WHO 71st Consultation on International Nonproprietary Names

Geneva, Switzerland – October 20-23, 2020

World Biosimilar Congress Europe 2020

Virtual – November 3-5, 2020

ACR Convergence 2020

Virtual – November 6-11, 2020