​Eleven months on from the initial outbreak of COVID-19 in China, the virus continues to be a hot topic around the world, generating vast interest due to the impact on personal freedom, finances, and health. To better understand the impact of the pandemic on different countries, we have previously published two reports:

• One at the end of April, discussing the different approaches to manage the spread of the outbreak,
•  The other at the start of July, focusing on how the pandemic was being monitored and the emerging impact on market access.

Now, as reports emerge of the first vaccine being approved for temporary use by the MHRA in the UK, we have compiled a third report summarising the latest methods to manage the pandemic in each market and the associated plans to roll out a vaccination programme.  Each report contains a summary of the latest statistics and a short article for a range of countries across the world, as written by a selection of FingerPost's Global Associates.

The November report provides a number of key insights, but one theme that particulary stands out is the different investment strategies for the vaccines being developed. There are currently more than 100 COVID-19 vaccines in development (48 in clinical evaluation, 164 in preclinical evaluation), with three of those close to receiving market authorisation by the main regulatory agencies across the world. From the vast media coverage of these three vaccines, it will be no surprise that these include the AstraZeneca/Oxford vaccine, Pfizer/BioNTech vaccine, and the Moderna vaccine. The three vaccines all require 2 doses but differ from the perspective of production methods, storage requirements, efficacy and cost per dose (ranging from $3 to $37 per dose).  Here is a quick summary of the differences and published investment plans for the three 'first to market' (excluding Russia and China) vaccines in development:

Further information on the various insights emerging from COVID-19 as of November 2020, are summarised in our latest report. The November report provides an overview from a range of markets:

• North America: USA, Canada
• South America: Brazil, Argentina
• Europe: UK, France, Germany, Spain, Italy, Sweden, Switzerland, Portugal and the Netherlands
• Asia Pacific: India, Indonesia, China, Taiwan, Singapore, Japan, South Korea, Australia and New Zealand.

Each summary is written by a Market Access expert with a specialist interest in the country they report on and provides a fascinating global insight. 

If you would like a copy of this report, or any of our previous reports, please contact cbacon@fingerpostconsulting.com or fill out the contact form for one of the FingerPost team to follow up. ​

In May this year, a new definition of HTA was announced following a collaboration co-led by the International Network of Agencies for HTA (INAHTA) and HTA International (HTAi).
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This is important as it provides insight into how the members of INAHTA and HTAi, as well as the other collaborations noted, are viewing the evolution of HTA. Previously, the various groups had their own definitions, now they are moving forward with the same focus, in the same direction.

The joint task group conducted three rounds of consultation to reach a consensus. Discussion focused on whether:

• the definition of a health technology needed updating (no);
  
• to include improving health outcomes as an aim, in addition to informing health policy and decision making (no);
  
• removal of jargon and simplification (yes); and
  
• how to express the concept of value (considered context-related). 
  

The change from ‘all available evidence’ to ‘best available evidence’ acknowledges that decisions must be made and pragmatism may be required.
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The general nature of the definition is meant to “reflect different decision contexts in low-, middle-, and high-income countries, such as: formulary coverage or reimbursement decisions (including disinvestment); clinical practice guideline development; defining emergency kits, disaster planning, (basic) benefit packages, and essential medicine lists; medical device and equipment procurement planning; negotiating prices for health technologies, and other decision contexts at the national, regional, or local levels, including hospitals”.

HTA is a versatile tool, and even though the definition may be quite general and succinct, how it came about says a lot.

Note 1: A health technology is an intervention developed to prevent, diagnose or treat medical conditions; promote health; provide rehabilitation; or organize healthcare delivery. The intervention can be a test, device, medicine, vaccine, procedure, program, or system.

Note 2: The process is formal, systematic, and transparent, and uses state-of-the-art methods to consider the best available evidence.

Note 3: The dimensions of value for a health technology may be assessed by examining the intended and unintended consequences of using a health technology compared to existing alternatives. These dimensions often include clinical effectiveness, safety, costs and economic implications, ethical, social, cultural and legal issues, organizational and environmental aspects, as well as wider implications for the patient, relatives, caregivers, and the population. The overall value may vary depending on the perspective taken, the stakeholders involved, and the decision context.

Note 4: HTA can be applied at different points in the lifecycle of a health technology, that is, pre-market, during market approval, post-market, through to the disinvestment of a health technology.
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Reference: O’Rourke B, Oortwijn W, Schuller T, the International Joint Task Group (2020). The new definition of health technology assessment: A milestone in international collaboration. International Journal of Technology Assessment in Health Care 36, 187–190.  https://doi.org/10.1017/S0266462320000215
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Over the past five years, a number of 'big brand' biologics have gone off patent and have been replaced with biosimilars. This remains a challenge for any biologic nearing the end of the lifecycle, no doubt pushing prices up to achieve maximum return on investment for the short time available on the market. At FingerPost, we have been involved with a number of research projects looking at the impact of biosimilars - both from the perspective of the biologics nearing the end of their patent, and from the perspective of new biosimilars preparing to launch. We thought it would be interesting to review the current biosimilar situation in Australia and Canada, particularly as trust in biosimilars has grown amongst payers and healthcare professionals with increasing experience over the past few years.

As of 1 July 2020, the Sanofi Lantus® brand of insulin glargine is no longer reimbursed to treat diabetes on the national Pharmaceutical Benefits Scheme (PBS). The first biosimilar brand of insulin glargine, Semglee® (Alphapharm) was PBS listed in October 2019. 

Commencing in 2015, the Australian Government has introduced successive initiatives to encourage prescribing and dispensing of biosimilar brands of biological medicines. The Semglee® brand of insulin glargine was assessed by the Therapeutic Goods Administration (TGA) to be highly similar, based on the FDA definition, to the reference brand Lantus®.  Such assessments are then translated into opportunities for substitution.

These are signalled on the PBS by the practice of flagging: 
 ‘a’ flagging denotes that: 

• Brand substitution may be undertaken by pharmacists at the point of dispensing without difference in clinical effect or health outcomes. 
• Brand substitution by pharmacists is permitted without reference to the prescriber when the following conditions apply: the patient agrees to the substitution; and the prescriber has not indicated on the prescription form that substitution should not occur by ticking the box labelled ‘brand substitution not permitted’. 

 While ‘b’ flagging denotes that:  

• the brand is equivalent to the reference brand but it is not known if there is equivalence to the ‘a’ flagged brand. 
• All medicines flagged ‘b’ are substitutable by the pharmacist when the patient agrees to substitution and the prescriber has not indicated on the prescription form that substitution should not occur. 

The Education arm of the Australian Generic and Biosimilar Medicines Association (GBMA) received a grant of AU 5 million dollars (US 3.5 million) from the Australian Government in April 2018 to increase confidence in the use of biosimilars via peer-to-peer health communication activities. A further driver is the October 2019 introduction of active ingredient prescribing regulations. These require prescribers to include the active ingredient on all PBS prescriptions. A brand name can be included after the active ingredient where doing otherwise may pose a patient safety risk. Prescribing software must be updated to reflect these requirements. There are concerns that prescribers will be unable to identify products by brand.   

Insulin glargine 100 units/mL listings on the PBS now include the following note:
Biosimilar prescribing policy 
Prescribing of the biosimilar brand, Semglee, is encouraged for treatment naive patients. Encouraging biosimilar prescribing for treatment naive patients is Government policy. A viable biosimilar market is expected to result in reduced costs for biological medicines, allowing the Government to reinvest in new treatments. Further information can be found on the Biosimilar Awareness Initiative webpage (www.health.gov.au/biosimilars). 
 
​So back to Lantus®, Sanofi introduced the Optsulin® brand (available overseas) in January 2020, under the same PBS code 9039R, as the formulation, excipients and manufacturing process are the same. It is ‘a’ flagged. Through a partnership with the Australian Diabetes Educators Association, Sanofi's insulin patients were able to call toll-free and speak with a Credentialled Diabetes Educator (CDE) about the transition. The commercial reason behind the re-branding exercise is unclear as the effective price of 100 units/mL has not changed. Special pricing arrangements (meaning a difference between the published and effective price) continue to apply to the Sanofi Toujeo Solostar® brand of insulin glargine 300 units/mL.

British Columbia:
British Columbia was the first province to initiate biosimilar switching policies. On May 27, 2019, BC PharmaCare launched the Biosimilars Initiative with the objective of switching patients using Enbrel®, Remicade®, and Lantus® for certain indications to their biosimilar versions by November 25, 2019. The second phase (September 5, 2019 – March 5, 2020) consisted of patients being switched from Remicade® for gastrointestinal (Crohn’s disease or ulcerative colitis) to a biosimilar version. The three biologic drugs selected for biosimilar switching were among the highest drug expenditures in BC, totalling $125 million in 2018. During the first phase of the initiative, 73% of 20,780 patients using the reference biologics were switched to biosimilars. During the second phase, based on initial partial numbers, 78% of patients on infliximab reference product were switched to biosimilars.

Alberta:
In Alberta, the government introduced the Alberta Biosimilar Initiative on December 12, 2019. This initiative requires adult patients currently on an originator biologic drug to switch to a biosimilar version, if available for their medical condition, in order to maintain drug coverage through the government sponsored drug plan. The products included in the Biosimilar Initiative are:

• Remicade® (all indications)
• Enbrel® (all indications except plaque psoriasis and pediatric juvenile idiopathic arthritis)
• Lantus® (all indications)
• Neupogen® (all indications)
• Neulasta® (all indications)
• Copaxone® (all indications)

Alberta spent over $238 million in the 2018 to 2019 fiscal year on biologics and with this initiative, the government anticipates saving approximately $30 million annually. The switching requirement was initially scheduled for July 1, 2020 but due to the COVID-19 pandemic, it was postponed to January 15, 2021.

Ontario:
On January 1, 2020, the Ontario Ministry of Health published a policy directive addendum to the Ontario Guidelines for Drug Submission and Evaluation which simplified requirements for biosimilar drug product submissions. The simplified submission no longer requires the biosimilar manufacturers to provide scientific evidence of clinical similarity between the biosimilar and its originator product – the rationale being that Health Canada does this assessment before approving the biosimilar. As a result, the biosimilar listing process on the public drug plan would be considerably quicker. In a report published by the Ontario Drug Policy Research Network (ODPRN) titled “Current and Prospective Utilization of Innovator Biologics and Biosimilars in Ontario,” a total of $1.1 billion was spent on biologic medications through the Ontario public drug program in 2018. The report found that biosimilar uptake in Ontario was low, with less than 1 in 5 biologic users accessing the available biosimilars.

Canadian Agency for Drugs and Technologies in Health (CADTH):
The Canadian Agency for Drugs and Technologies in Health published a report in January 2020 titled "Utilisation of Innovator Biologics and Biosimilars for Chronic Inflammatory Diseases in Canada: A Provincial Perspective." The report addressed the findings of the ODPRN report and provided possible cost-containment mechanisms or strategies to optimize the benefits associated with biosimilar drugs alongside innovator biologics. The proposed possible approaches provided include:

• Controlled substitution of innovator biologics for biosimilars
• Reimburse biosimilars for newly diagnosed persons only – persons already being treated with an innovator biologic drug may remain on that treatment if their disease is stable
• Tiered reimbursement for innovator or biosimilar biologics – “tiers” would be based on the medicines’ relative value for money, with the most cost-effective options classified in the first reimbursement tier
• Prescribing quotas to incentivize use of biosimilars
• Provide access to biosimilars using tendering procedures

 
Physicians and Patients:
Lastly, what is the perspective of physicians and patients with regard to the biosimilar initiatives? The Canadian Association of Gastroenterology and Crohn’s Colitis Canada published the "Joint Canadian Association of Gastroenterology and Crohn’s Colitis Canada Position Statement on Biosimilars for the Treatment of Inflammatory Bowel Disease"

Included in their recommendations:

• A biosimilar may be started in patients who are naive to anti-TNF therapy rather than starting with the biologic originator but this is contingent on the price differential of the two drugs. If the price differential is modest, then the biologic originator should be used.
• Nonmedical switching from the originator biologic to biosimilar in patients whose disease is stable with treatment is not recommended.

Biosimilar policies will continue to evolve across Canada as public payers must balance managing their drug plan budgets while meeting  patient needs. Adding further complexity to this issue is the COVID-19 pandemic, the long-lasting impact of which remains unknown.

At the end of April, we published a summary of the global response to COVID-19 as written by a selection of FingerPost's Global Associates who specialise in Market Access across different countries. The summary (available here) provided a brief overview of the statistics as they were at the end of April, measures implemented to reduce the outbreak and any other impact (political, economic or social) on each market as a result of the pandemic. This was a valuable snapshot ahead of the first steps taken to ease 'lockdown' measures across Europe and the US. However, this was far from the end of the pandemic and there was still a lot of uncertainty surrounding when and where  'second wave' outbreaks would occur. 

Two months on, we have now published a follow up to the report to capture the continued impact of the pandemic. During this time, we have seen widespread outbreaks of COVID-19 shift from Europe and North America, through to Latin America, India and Pakistan. Brazil, in particular, is one of the worst hit with no sign that the pandemic has reached its peak. Meanwhile, widespread resurgences of the virus have also been documented in the US and Asia, as per the predictions for 'second wave' outbreaks. Local surges have also been documented in most of the countries 'recovering' from the initial outbreak but these are being managed via local restrictive measures, as well as nationalised tracing programs. 

Various regulations have been relaxed to help ensure rapid access to medicines, devices, healthcare apps and personal protective equipment to help treat those with COVID-19, protect healthcare workers and prevent or identify further outbreaks. For example, in Spain protective masks that do not bear the appropriated CE mark (NIOSH or KN95) can now be commercialised. Many countries have also centralised pricing and supply/distribution systems to ensure an adequate supply of medicines.

Remdesivir has now received EMA and FDA marketing authorisation for COVID-19, and will be distributed by Gilead for patients on government-sponsored insurance in the US and other countries with national healthcare systems. In India and 126 other low- and middle-income countries, four Indian companies have been granted non-exclusive licences to produce remdesivir for distribution. 

As the pandemic shows no sign of slowing on a global level, there are strong hopes for the 17 candidate vaccines in clinical evaluation and 132 in pre-clinical evaluation. AstraZeneca has already started to manufacture a vaccine that has been co-developed with scientists at Oxford University, which will be supplied to low- and middle-income countries via a licensing agreement with Serum Institute of India (SII). This is a big risk as they won't know until August whether the AZD1222 vaccine will be effective. Similarly, in the United Arab Emirates, the Abu-Dhabi-based Group 42 (G42) are partnering with the Chinese pharmaceutical giant Sinopharm China National Biotec Group (CNBG) to commercialise and develop a vaccine. And in Germany, €750 million has been allocated by the government to go towards vaccine development and to aid the international Coalition for Epidemic Preparedness Innovations. 

Despite the COVID-19 pandemic, there is still a need to keep bringing other medicines to market. This is recognised by the majority of health technology assessment (HTA) agencies, who have continued to evaluate new treatments throughout the various 'lockdowns'. However, the Scottish Medicines Consortium (SMC) have experienced some delays and now expect to resume their meetings in August. Likewise, in Canada, the pan-Canadian Pharmaceutical Alliance (pCPA) have indicated that some negotiatons may be temporarily put on hold or delayed.

At FingerPost, we anticipate a more challenging Market Access environment over the next few years. Firstly, a number of 'non-urgent' medical appointments (e.g. cancer screening, minor surgeries, GP appointments) have been postponed throughout the pandemic. This is likely to have long-term consequences for the management of chronic conditions.  Secondly, those who have 'recovered' after receiving intensive care for COVID-19 symptoms are likely to require long-term support to manage the damage left by the virus, the extent of which is largely unknown. And finally, financing COVID-19 is likely to take it's toll on global healthcare systems, exerting additional pressure on pricing and reimbursement negotiations to reduce the cost of medicines. 

If you'd like to read more about the global impact of COVID-19 as of the 30th June 2020, you can download our latest 'Global snapshot of COVID-19' report below for free. The report contains summaries for 22 different global markets, with key insight from the FingerPost team and our Global Associates. I'd like to say a big thank you to all of the authors who contributed content to this report and hope you find the summaries as interesting as I did.