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Lessons learnt can inform the use of a new generation of biosimilar products

By Jenny Bryan

As biological products make up a growing part of the annual £12.5bn NHS drugs bill, procurement and specialist pharmacists are assessing how biosimilar brands may take their place alongside traditional generic products in reducing prescribing costs. sandoz manufacturing site

Currently available in just three therapeutic areas — erythropoietins (EPOs), granulocyte colony stimulating factors (G-CSFs) and growth hormone — today’s biosimilars are having a modest impact on the secondary care drugs bill. But the ongoing patent expiries of big brand biologicals, such as Remicade (infliximab), MabThera (rituximab), Herceptin (trastuzumab) and Enbrel (etanercept), carry much greater potential for savings within both primary and secondary care.

Lessons learnt from the introduction of today’s biosimilars could therefore have important implications for getting the most out of the next generation of products. 

G-CSF: the Yorkshire experience

In the 12 months since switching part of their G-CSF prescribing to biosimilar brand Zarzio, Yorkshire cancer specialists have saved nearly £1m. They still tailor their G-CSF use to the particular needs of their patients, but their significant savings are helping to offset the rising costs of other cancer drugs.

“The vast majority of our G-CSF use is now biosimilar filgrastim, but physicians still have the option of prescribing the original brand of filgrastim, Neupogen, or pegfilgrastim or lenograstim in situations where the evidence for their use is stronger,” explains Phil Deady, lead pharmacist, procurement, Leeds Teaching Hospitals NHS Trust.

Such a major change in regional procurement did not happen overnight, and Mr Deady traces its success back to the introduction of therapeutic tendering several years ago. At that time, a major review of efficacy and safety data of branded G-CSF drugs was carried out and presented to oncologists, cancer nurses and pharmacists across the region.

Agreement was reached that where evidence-based outcomes were the same, decisions about purchasing would be based on cost. When new brands were introduced, rigorous assessments were carried out by Mr Deady and his team so that clinicians could be confident that patients continued to get the most effective treatment while savings were being made.

Preparing for biosimilars

There are a number of ways in which pharmacists can prepare themselves for increasing use of biosimilars in the future:

Establishing resources

Carrying out safety and efficacy comparisons of standard and biosimilar biologicals requires pharmacy procurement, quality assurance and medical information expertise. So it is essential to work with primary and secondary care chief pharmacists and trust senior management in order to gain resources.

Spreading the word

Hospital procurement pharmacists regularly discuss new operational initiatives, such as those relevant to biosimilars, at meetings of the Pharmaceutical Market Support Group. Attending meetings can help establish which approaches could be applicable in other regions, with medicines procurement specialists taking information back to their areas of work for further discussion. Similarly, the National Pharmaceutical Supply Group provides strategic insights into cost-effective procurement.

Interacting with primary care

The development of GP commissioning and the expansion of the biosimilar market as major biologicals come off patent mean that more decisions about biosimilar purchasing could be made jointly with primary care. So it is important for pharmacists to explain how biosimilar initiatives in secondary care might extend to primary care.

Having got used to the process with branded G-CSF drugs, Yorkshire cancer specialists responded positively to the idea of a similar approach when biosimilars of filgrastim became available.

“The main difference was that there was much smaller patient experience with biosimilars than with branded products because biosimilar clinical trials are smaller. So clinicians wanted to understand the licensing process and be convinced that they were getting the same efficacy and safety with the biosimilar brands,” Mr Deady explains.

Several months of analyses and presentations, including a meeting at which clinicians were able to challenge biosimilar manufacturers over their data, culminated in a decision to use less pegfilgrastim and more filgrastim — for which biosimilar brands were being launched. It was also agreed that Yorkshire would continue to buy lenograstim for paediatric indications and some original brand filgrastim for units carrying out bone marrow transplants because data were not available at that time to support biosimilar filgrastim in this indication.

Having agreed levels of need for the different types of G-CSF, it was left to the procurement team to negotiate the best deals with all the manufacturers. For biosimilar filgrastim, it was the Sandoz product, Zarzio, that took the business.

“Our previous spend on G-CSF in Yorkshire was about £2m per year, and we have made savings of just under £1m in the first year. However, we think those savings will increase as clinicians have found they are reducing their use of pegfilgrastim more than they expected,” says Mr Deady.

The framework agreement that Yorkshire has set up for purchasing its G-CSF allows flexible use of the agreed brands with various price breaks for two years. There is the option of a two-year extension.

“It had to be flexible because if other companies do pivotal trials with their G-CSF in an important indication, we need to be able to switch to that brand if the results are better than for the product we are currently using. Our clinicians need to be sure that cost only becomes a consideration after we have shown comparable safety and efficacy,” adds Mr Deady.

G-CSF: the Birmingham experience

In Birmingham, biosimilar filgrastim has been in use for about a year but, as in Yorkshire, there has not been a total switch from original G-CSF brands. Nick Duncan, principal pharmacist, haematology/oncology, at University of Birmingham NHS Foundation Trust, explains that the trust decided to use biosimilars in the management of neutropenia induced by standard or high-dose chemotherapy. But consultants agreed that they would extend the European Blood and Bone Marrow Transplantation Group advice not to use biosimilars to mobilise stem cells in healthy donors, to include patients requiring stem cell mobilisation as well.

“They made the decision on the basis of concerns about efficacy as well as safety, as there was uncertainty over whether the biosimilar brands would be as effective in mobilising stem cells as the conventional brands we were used to,” says Mr Duncan. “It was felt that if there was reduced efficacy with biosimilar filgrastim in a neutropenic patient then that may mean prolonging treatment by a day or two. But if we couldn’t get enough stem cells for a transplant procedure that would be much more of a problem.”

Mr Duncan was involved in contractual discussions with biosimilar manufacturers, including those on pricing issues, and liaised with clinicians and nurses before developing guidance about appropriate use of biosimilar filgrastim within the trust.

“The logical next step will be to audit outcomes to see whether neutrophil counts recover at the same rate with biosimilars as with the original brands, but there’s been no anecdotal information of a problem,” says Mr Duncan.

EPOs: the Liverpool experience

Biosimilar brands have not yet made any inroads into EPO use in Liverpool or the north west mainly because, as short acting agents, they can only compete with older EPO brands, such as Eprex and NeoRecormon, rather than the newer patient-friendly long-acting agents, such as Aranesp and Mircera.

“The discounts on EPO prices are substantial, whatever brand you buy, and hospitals which place large orders can already get long-acting drugs, such as Aranesp, at comparable prices to the older, short-acting drugs,” explains John Sexton, principal pharmacist renal services, Royal Liverpool University Hospital.

sandoz manufacturing siteLingering concerns about the potential for rare side effects, such as pure red cell aplasia, which emerged as a very rare but serious problem with subcutaneous Eprex in the early 2000s, have also contributed to a reluctance to prescribe new EPO brands with limited clinical experience, as tends to be the case with biosimilars.

“In addition, there is the issue that changing a patient from one brand to another takes a lot of work, and can take months. So once a patient is settled on one brand, we do not really want to start moving them around,” Mr Sexton points out.  

He explains that the largest market for EPOs is the haemodialysis population, and some hospitals tend to pay for treatment of these patients through bulk contracts, leaving GPs to pay for EPO treatment of pre-dialysis chronic kidney disease (CKD) and peritoneal dialysis, often at list prices. But contracting could become even more competitive with GP commissioning, as consortia demand rock-bottom EPO prices for all their renal patients.

Any company bidding to supply EPO also has to factor in the cost of home delivery — something that was not a consideration when firms were deciding to develop EPO biosimilars since dialysis was a hospital-based therapy, with few patients treating themselves at home.

“The EPO landscape changed enormously during the time that companies were developing their biosimilars and made it much harder for them to compete than they had expected. Bulk buying of cheap, long acting EPOs, often through regional contracts, with the requirement to provide a home delivery service, have made it a very tough market to get into,” Mr Sexton concludes.

Somatotropin: the London prediction

Licensed by the European Medicines Agency in 2006 for the treatment of child growth deficiencies, Omnitrope (somatropin) was the first biosimilar to be made available in the UK. In 2010, it became the first biosimilar to be included in NICE guidance — as one of seven forms of somatropin recommended for the treatment of growth failure in children with growth hormone deficiency.1

In support of its European licence application, Omnitrope powder went head to head with the original biological, Genotropin, and was associated with a similar increase in patient height over a nine-month period of treatment. Comparable safety was reported, although a higher level of anti-human growth hormone (HCG) antibody production was reported with Omnitrope than Genotropin (58.5 per cent vs 2.3 per cent), and was subsequently attributed to high concentrations of host cell (Escherichia coli) protein in the powder formulation of Omnitrope.2,3

Additional purification steps were introduced and resulted in levels of antibody formation during the remainder of the study comparable to those seen with Genotropin (7 per cent between months 15 and 84), and there was no evidence of any impact of antibody formation on growth response during the seven-year study.

Based on growth hormone usage at University College London Hospital (UCLH) Trust, principal pharmacist Anthony Grosso and colleagues recently calculated that use of Omnitrope could generate local savings in excess of £200,000 per year.3 However, they point out that convenience and stability of the somatropin formulation are also important considerations.

Both Omnitrope and Genotropin are available as ready-to-use multidose solutions for daily subcutaneous injections. But Genotropin and the single-use preparation, Genotropin MiniQuick, do not require refrigeration and the UCLH team suggests that the latter product is particularly useful for patients on holiday without refrigeration facilities.

They add that, given the age of the patient group, it is also important that those with a needle phobia have the opportunity to use a needle-free device, such as Zomajet Vision X. Indeed, they point to the considerable amount of clinic time needed to discuss the pros and cons of all the delivery devices for somatropin products with their young patients, in order to ensure that they will be happy with their choice.

Conclusions

In common with generic prescribing, there is more to using biosimilars than cutting costs. After only a few years of biosimilar experience, in just three therapeutic areas, it is clear that prescribers need both original biologicals and biosimilars to accommodate the differing clinical needs of their patients. The Yorkshire experience of biosimilar G-CSF use demonstrates the value of investing in the skills and resources needed to conduct high quality evidence reviews capable of showing clinicians that, while different from familiar biological brands, biosimilars can match up on safety and efficacy, and that a robust regulatory framework exists to test this.

The Birmingham experience also showed that, where there is good evidence, clinicians are prepared to incorporate biosimilars in their routine practice. But it demonstrates a preference for a step-by-step approach, with opportunities to gain local experience before making a large-scale transfer to the biosimilar route.

Experience with EPOs has shown that pharmaceutical companies committed to innovation in biological products will not be handing their markets over to the biosimilar firms without a struggle. By the time that producers of biosimilar EPOs had negotiated the demanding regulatory requirements for getting their brands on the market, the goalposts had moved and the new biosimilar EPOs had to compete with easier-to-use brands and a big increase in home dialysis.

Finally, the growth hormone market has shown that, while potential savings from biosimilars may be significant, patient preferences still count, especially when it comes to children.

That said, major biosimilar producers, such as Sandoz, Teva and Hospira, are already leaders in the traditional chemical generics market, and will not have much to learn about competing with established “big name” biologicals at levels other than just price. But given that traditional generics only make up 20 per cent of the NHS drugs bill, despite representing 80 per cent of prescribing by volume, there are still plenty who question whether even large scale use of biosimilars in the next 10 years can make the level of savings to NHS drugs budgets that are needed.

References

1        National Institute of Health and Clinical Excellence. Human growth hormone (somatropin) for the treatment of growth failure in children. Review of NICE technology appraisal guidance 42, 2010.

2        Romer T, Saenger P, Peter F, Walczak M, Le Bouc Y, Khan-Boluki J, et al. Seven years of safety and efficacy of the recombinant human growth hormone Omnitrope in the treatment of growth hormone deficient children: results of a phase III study. Hormone Research 2009;72:359–69.

3        Thakrar K, Bodalia P, Grosso A. Assessing the efficacy and safety of Omnitrope. British Journal of Clinical Pharmacy 2010;2:298–301.

Citation: The Pharmaceutical Journal URI: 11078938

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