Sweden's TLV grants reimbursement to three drugs, including Fabry treatment Galafold and orphan drug Raxone for treating LHON

The Swedish Dental and Pharmaceutical Benefits Agency (TLV) announced that it has listed Galafold (migalastat; Amicus Therapeutics, US) as an option for the treatment of Fabry disease in patients aged over 16 years, with amenable mutations, as well as the orphan-designated drug Raxone (idebenone; Santhera, Switzerland) for the treatment of adult and adolescent patients with the rare genetic condition Leber's hereditary optic neuropathy (LHON). The favourable reimbursement decisions are worth highlighting since they follow relatively shortly from European Commission final market authorisation approval (see Europe: 1 June 2016: Amicus Therapeutics secures European Commission approval for Galafold in Fabry disease and Europe-Switzerland: 10 September 2015 Switzerland's Santhera Pharmaceuticals receives European Commission market authorisation for Raxone in treating Leber's hereditary optic neuropathy).

Oral treatment Galafold approved for reimbursement in treating Fabry disease

The TLV's reimbursement decision marks the first major reimbursement approval of Galafold in the European Union (EU), although the United Kingdom's National Institute for Health and Care Excellence (NICE) issued a positive recommendation for the drug in October, provided a confidential discount agreement could be reached with Amicus as part of a patient access scheme (PAS). The orphan-designated drug has also been launched in Germany. The TLV approved Galafold as a long-term treatment option for adult and adolescent Fabry disease patients (aged 16 years and over) with amenable mutations, which cover between 30% and 50% of cases. The TLV's judgment (available in Swedish here) was that Galafold provided similar health benefits to enzyme replacement therapy (ERT), the current standard treatment for Fabry disease, but at lower cost. The cost-effectiveness evaluation compared Galafold with the enzyme replacement therapies Fabrazyme (agalsidase beta; Genzyme, United States) and Replagal (agalsidase alfa; Shire, Ireland). The Swedish agency also accepted that Galafold provided additional health benefits for Fabry disease patients, since it is taken orally, rather than requiring an infusion every two weeks like ERT. Approval was based on results of the ATTRACT and FACETS clinical trials and two open-label extension studies. The list price of Galafold is SEK10,798 (USD1,204) per capsule and the annual cost of treatment is estimated at SEK1.97 million per patient. The cost-effectiveness evaluation does not provide figures on how many Fabry disease patients could be candidates for Galafold in Sweden. However, the TLV has noted elsewhere that the number of candidates is likely to be very low. Nevertheless, patient groups have welcomed the decision and are expected to benefit from the oral option, since it will have greater patient convenience and freedom over fortnightly infusions. The entry of Galafold to the market will therefore present a serious sales challenge to standard enzyme replacement therapies in Sweden.

Reimbursement of Amicus Therapeutics' Raxone in LHON is its first in Europe

The Swiss pharmaceutical company Santhera has gained TLV-reimbursement clearance for Raxone (idebenone) in the treatment of adult and adolescent patients with the rare heritable genetic condition LHON. The mitochondrial disorder causes visual impairment resulting in progressive, rapid, and permanent bilateral blindness. The reimbursement approval was based on clinical trial data from a Phase III (RHODOS), which demonstrated that Raxone was effective in mitigating further vision loss in patients with LHON. The drug has also been shown to reverse some visual damage, achieving a meaningful improvement in visual acuity. The orphan-designated drug is the first LHON medication that will be available in Sweden.

The dosing regimen for Raxone involves being taken as an oral medicine with a daily defined dose (DDD) of 900 mg (divided as two 150 mg tablets taken three times per day).

At the time of writing, the TLV has yet to publish a full cost-effectiveness evaluation for Raxone.

The TLV estimated that 200 patients are affected by the inherited condition, with an average of five to seven new LHON cases diagnosed each year. The price negotiations for the drug were conducted on the basis of tripartite discussions between the pricing and reimbursement (P&R) agency, the pharmaceutical sector, and regional councils (landsting) as part of a national process for value-based pricing. Under this framework, Santhera has agreed to a pricing and risk-sharing model with the country's local county councils linked to uncertainties over the effectiveness of Raxone and the number of patients expected to be treated. This represents the first occasion when this tripartite reimbursement mechanism has been used to approve an orphan-designated drug in Sweden, according to the TLV. Such risk-sharing agreements are more likely to follow in future (see Sweden: 29 September 2016: TLV reimburses Zepatier and Epclusa, authorities indicate Sweden is prepared to accept higher prices for orphan medicines).The manufacturer will be required to provide additional data on the number of patients treated with Raxone by 30 April 2018.

Symbicort inhaler added to Sweden’s reimbursement list

AstraZeneca (UK)'s Symbicort Turbohaler (budesonide-formoterol inhalation powder) has also been approved for reimbursement for the treatment of chronic obstructive pulmonary disease (COPD) with forced expiratory volume in one second (FEV1) of 50–70% predicted normal (post-bronchodilator) and an exacerbation history despite regular bronchodilator therapy. The full cost-effectiveness evaluation is available in Swedish here. Symbicort Turbohaler was determined to be cost-neutral when compared with Chiesi Farmaceutici (Italy)'s COPD drug Fostair (beclomethasone dipropionate), according to the TLV. In addition, since it has about the same price as the relevant benchmark option at an intermediate dosage level, it was included in the reimbursement list from 28 October.

Novartis's Xolair reimbursed to treat CSU

Novartis's Xolair (omalizumab) was cleared for a severe chronic spontaneous urticarial (CSU) indication, as announced in a separate decision on 31 October. The drug was not deemed to be cost effective for moderate CSU. The full evaluation is available in Swedish on the TLV website here. Xolair gained marketing approval in the European Union for the treatment of CSU in March 2014. The drug is already reimbursed in Sweden in an asthma indication. The approval is based on a number of recent Phase III trials (including ASTERIA I, ASTERIA II, and GLACIAL studies) demonstrating that Xolair produced substantial improvements in quality-of-life measures. Patients receiving treatment with Xolair for 12 weeks experienced a 78% improvement in quality of life, as measured by the Dermatology Life Quality Index (DLQI), against 44% with placebo. When measured using the Chronic Urticaria Quality of Life Questionnaire (CU-Q2oL), the improvement was 69% for the Xolair arm versus 40% for placebo (see Switzerland: 17 June 2015: Phase III analysis shows Novartis's CSU treatment Xolair leads to substantial improvement in quality of life).

Outlook and implications

The listing of these medicines for reimbursement is a positive development for the manufacturers. The inclusion of the orphan designated drugs Raxone and Galafold in particular is likely to be welcomed by patient groups and should pave the wave for the expansion of sales by Santhera and Amicus in Sweden. The positive reimbursement decisions for Xolair in a CSU indication and for AstraZeneca's Symbicort Turbohaler in COPD is also likely to boost their sales in the country. Although a medium- to small-sized markets, Sweden is a well-positioned market for early reimbursement decisions and these approvals could signal a favourable outlook for reimbursement decisions in other EU countries, notably the Nordic nations.