August 2, 2018 Sean Skulski

Navigating HTA: AstraZeneca’s Fasenra and NICE

A Pricentric Brief

by Sean Skulski

According to the World Health Organization (WHO), Health Technology Assessment (HTA) is a multidisciplinary, systematic evaluation of the properties, effects, and/or impacts of health technology to inform a policy decision making. During HTA, authorities evaluate the social, economic, organization, and ethical issues of a health intervention or health technology.

When a manufacturer is seeking approval for a new drug, demonstrating cost-effectiveness in comparison to existing, comparator treatments, a key criterion of HTA, is not always an easy task; at times, the journey can feel circuitous and, depending on the succinctness of a submitted dossier, the process can be two steps forward, and one step back.

AstraZeneca’s (AZ) Fasenra (benralizumbab) has favored well overall in Europe, but the asthma medication has had an uphill battle, competing with pre-existing therapies, GlaxoSmithKline’s Nucala (mepolizumab) and Teva’s Cinqaero (reslizumab). This past week, the UK’s National Institute for Health and Care Excellence (NICE) recommended the drug, but with a catch: Fasenra should be used only when comparative therapy Nucala is not an option.

Key players in Europe and the UK

Once the European Medicines Agency (EMA) grants marketing authorization of a new active substance, based on a positive recommendation from its Committee for Medicinal Products for Human Use (CHMP), Member States of the European Union (EU) will conduct their own HTA before entering pricing and reimbursement negotiations with pharmaceutical companies. Every drug undergoes HTA, which is used to demonstrate the clinical efficacy and cost-effectiveness of a drug compared to existing treatments.

According to Pricentric One’s Country Overviews modules, this is especially the case in the United Kingdom. While the UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) conducts HTA akin to the EMA (and up until news of Brexit, MHRA had been closely-linked with EMA), NICE performs cost-benefit analysis. NICE weighs the cost of the drug to the national health system (NHS) against appropriate treatments already approved for use within the NHS, along with ensuring that the foreseen quality-of-life (QoL) benefit is no higher than the standard £30,000 per QALY.

Because of NICE’s cost-consciousness, a pharmaceutical company needs to have a solid economic model for a new substance. To alleviate pressure on pharmaceutical companies when drafting an economic model, the NICE Scientific Advice (NAS) launched a new health economic model review service entitled Preliminary Independent Model Service (PRIMA). PRIMA offers model developers independent expert advice on the robustness and technical rigor of their economic model to gain approval in the UK.

NICE represents England, Wales, and Northern Ireland, although Wales has its own medicine agency, the All Wales Medicines Strategy Group (AWMSG); nonetheless, AWMSG follows NICE guidance. In Scotland, the Scottish Medicines Consortium (SMC) conducts HTA and cost-effectiveness analysis apart from NICE, although the Scottish HTA authority refers to NICE if guidance is available. But occasionally, drugs might be available in Scotland but not in England and vice versa.

The case with Fasenra

The chart above details HTA approvals for AZ’s Fasenra, along with its competitors, GSK’s Nucala and Teva’s Cinqaero.

 

In November 2017, AstraZeneca’s anti-IL-5 monoclonal antibody Fasenra, indicated in the treatment of severe eosinophilic asthma, was given a positive recommendation by CHMP, and in January 2018, EMA approval. Shortly thereafter, Fasenra was launched in the United Kingdom in April 2018.

This past week, the United Kingdom’s price-conscious drug assessment body NICE approved AZ’s Fasenra for the treatment of severe eosinophilic asthma—but with a catch. Although Fasenra was approved, NICE limited the patient group to those with high counts of eosinophilic cells who have had at least 3 exacerbations within the past year, and for whom treatment with GlaxoSmithKline’s already-existing, anti-IL-5 monoclonal antibody Nucala is not an option.

Fasenra’s appraisal committee examined clinical evidence from AZ’s SIROCCO, CALIMA, and ZONDA randomized-controlled studies, which compared Fasenra with placebo in people with uncontrolled asthma, taking inhaled corticosteroids and a long-acting beta antagonist, to conclude that the active substance (benralizumab) is clinically effective as an addition to standard care in patients with a blood eosinophil count of at least 300 cells per microliter, who have had 3 plus exacerbations, or are taking maintenance oral corticosteroids. NICE highlighted that the benefit would be greater for patients who have experienced more exacerbations with higher eosinophil counts.

The appraisal committee determined that the clinical effectiveness of Fasenra compared with Teva’s Cinqaero, another anti-IL-5 monoclonal antibody already available for use within the NHS, and GSK’s Nucala is uncertain. In its appraisal of Fasenra, the committee noted that compared to Cinqaero, AstraZeneca’s asthma drug is a cost-effective use of NHS resources. But, people within Fasenra’s indicated treatment group (i.e. people who have had 3 or more exacerbations or are taking maintenance oral corticosteroids) are also eligible for treatment with Nucala.

As such, NICE stated in its guidance: “Benralizumab [Fasenra] is therefore recommended as an option for treating severe asthma in people with an eosinophil count of 400 cells per microliter or more, who have had at least 3 exacerbations in the past year, only if Nucala is not a treatment option.”

A Look at the numbers

NICE recommended that Fasenra is not as cost-effective as Nucala and thus, cannot be recommended over Nucala. But when compared to Cinqaero, Fasenra is a cost-effective use of NHS resources.

Per NICE guidance, Nucala is recommended as add-on treatment for severe refractory eosinophilic asthma in adult patients. The recommended dosage of Nucala is 100 MG administered subcutaneously once every 4 weeks. Treatment efficacy should be re-assessed annually, although Nucala is noted to be a long-term treatment.

According to data from Pricentric One, the annual MNF cost of treatment based on Nucala Injection 1 Lyophilized Powder Vial 1.2 ML 100 MG is £10,800.00.

Like Nucala, Cinqaero is recommended by NICE as “an add-on therapy in adult patients with severe eosinophilic asthma inadequately controlled despite high-dose inhaled corticosteroids plus another medicinal product for maintenance treatment.” Recommended dosing is based on body weight. Patients weighing between 35 and 199 KG will receive be administered an intravenous infusion, vial-based dosing scheme every 4 weeks. For patients above or below the weight threshold, the recommended dosage is intravenous infusion every 4 weeks, 3 MG/KG of body weight.

According to data from Pricentric One, the annual MNF cost of treatment based on Cinqaero Infusion 1 Vial 10 ML 100 MG is £12,599.75, with an annual MNF cost plus wastage of £17,999.64. And based on Cinqaero Infusion 1 Vial 2.5 ML 25 MG, the annual MNF cost of treatment is £12,598.99, with an annual MNF cost plus wastage of £13,498.32. Cinqaero is costlier than Nucala.

For AZ’s asthma drug, the recommended dosage is 30 MG every 4 weeks for the first 3 doses, then 30 MG every 8 weeks, given by subcutaneous injection. Fasenra requires less frequent administration, but according to Pricentric One, its annual MNF cost of treatment, based off Fasenra Injection 1 Pre-filled Syringe 1 ML 30 MG is £15,500.36. Its cost is a lot higher than Nucala, but on the other hand, considering the wastage noticed with Cinqaero, it’s evident that Fasenra is a better, more cost-effective choice for treatment, which NICE noted in its guidance.

Fasenra across the board

NICE’s northern counterpart, the SMC has yet to offer an opinion on Fasenra, but once NICE greenlights or rejects a drug, Scotland follows suit soon after and vice versa. But, the agencies do not always agree, and drugs can be approved in Scotland, but not in England, Wales, and Northern Ireland.

In Scotland, Teva’s Cinqaero is not recommended for use within NHS Scotland, albeit the drug decreased incidences of exacerbation and improved lung function in adult patients with severe eosinophilic asthma. The drug was turned down in December 2017 because, according to SMC, there was a lack of “sufficiently robust economic analysis.”

Meanwhile, GSK’s Nucala, which was less expensive for NHS England and preferred by NICE, was recommended by SMC in June 2016 as an add-on treatment for severe refractory eosinophilic asthma in adults.

Like the UK, when EMA says yes to a drug, Germany will usually launch the product a few months after the approval. As part of AMNOG, a drug has one year of free pricing while Germany conducts HTA. While conscious of cost, Germany’s higher and lower HTA bodies, the Federal Joint Committee (G-BA) and the Institute for Quality and Efficiency in Health Care (IQWiG) respectively, focus on additional benefits without explicit consideration of the cost.

Fasenra was launched in Germany in February of this year. Commissioned by the G-BA to conduct an initial assessment, Germany’s lower HTA body IQWiG saw no added therapeutic benefit for Fasenra when compared to existing treatments; the low rating was attributed to a lack of sufficient data.

Even German medical journal Arznei-Telegramm, independent of the pharmaceutical industry, recommended GSK’s Nucala (launched in Germany February 2016) over Fasenra—and even over Cinqaero (launched in Germany January 2017). Arznei-Telegramm’s reasoning was that Nucala is cheaper, although before entering price arbitration in Germany, the asthma drug was too high; in May 2017, Nucala underwent a 27% price cut.

  • Based on Fasenra Injection 1 Pre-filled Syringe 1 ML 30 MG, the annual MNF cost of treatment with Fasenra is €21,902.68.
  • Based on Nucala Injection 1 Lyophilized Powder Vial 1.2 ML 100 MG, comparator Nucala’s annual MNF cost of treatment is €14,384.31.

Like Arznei-Telegramm advised, Nucala is a much cheaper treatment.

Next to offer a recommendation on Fasenra will be the G-BA. When G-BA compiles its recommendation, the higher HTA authority takes into consideration IQWiG’s rating; however, final decisions on the level of additional benefit provided by a new therapy are ultimately up to the G-BA. In the case of Nucala and Cinqaero, IQWiG concluded that each drug had “no additional benefit, whereas the G-BA rated each as offering “minor added benefit.” In general, once the G-BA offers its recommendation on a drug, Germany then enters pricing and reimbursement negotiations with the drug’s manufacturer. After undergoing pricing and reimbursement negotiations, Nucala took a 27% price cut in May 2017, and in January of this year, Cinqaero took a 7% price cut.

Takeaways

Most European countries conduct HTA. Because the United Kingdom is quick to launch a drug shortly after EMA approval and many countries rely on UK pricing to establish price ceilings, it is important to understand the dynamics of the UK approval process, particularly its adherence to cost-effective analysis.

For manufacturers seeking an optimal launch, Pricentric One recommends that a drug should clearly demonstrate product value, and manufacturers must carefully tailor economic and clinical arguments to justify optimal reimbursement. It is crucial for pharmaceutical companies to improve clinical trial design and early product selection to support economic arguments when going to market. Connect with HTA authorities, such as NICE, before the submission period to get advice.

As seen with Fasenra, NICE left no stone unturned while analyzing its cost-effectiveness compared to existing therapies. Fasenra beat out Cinqaero but lost to Nucala, the latter ultimately being deemed the more cost-effective treatment. Fasenra will be available for use within the UK’s NHS, but for a selection of patients with severe eosinophilic asthma for whom Nucala is not a treatment option.

Looking towards the future, which seems to have already arrived now that EMA approved its first immunotherapies, Novartis’ Kymriah (tisagenlecleucel) and Gilead’s Yescarta (axicabtagene ciloleucel), the UK has been opting for risk-sharing agreements. For drugs that cross the £30,000 QALY threshold, the UK will designate innovative status and drugs may thereby enter risk-sharing agreements. While Fasenra was not labeled as innovative because its annual cost remained below the QALY threshold, new drugs such as Kymriah and Yescarta, which bear hefty price tags, demand a need for cogent and evidence-based economic strategizing to seek a “thumbs up” from NICE.

Pricentric One tracks drug approval and launch dates and consistently monitors price changes. Additionally, negotiated MNF rates can be found in Pricentric One, all under the “Pricing” module.