SMC's August recommendations include Imbruvica, Tresiba, Praluent, Quinsair, Opdivo, and Cosentyx

Scotland’s health technology assessment agency, the Scottish Medicines Consortium (SMC), issued 13 decisions in August for funding of new medicines, including: full approvals for Imbruvica (ibrutinib, Johnson & Johnson (J&J) (US)) for mantle cell lymphoma MCL), Tresiba (insulin degludec, Novo Nordisk (Denmark)) for diabetes, Ayendi (diamorphine hydrochloride spray, Gilead Sciences (US)) for severe pain in children and adolescents, and Descovy (emtricitabine + tenofovir alafenamide, Gilead) and Edurant (rilpivirine, J&J) for HIV infection; and approval under restricted use for Praluent (alirocumab, Sanofi (France)) for hypercholesterolaemia, Imbruvica for chronic lymphocytic leukaemia (CLL), Quinsair (levofloxacin, Raptor Pharmaceuticals (US)) for chronic Pseumonas aeruginosa infections in cystic fibrosis patients, Opdivo (nivolumab, Bristol-Myers Squibb (BMS) (US)) for advanced melanoma, and Cosentyx (secukinumab, Novartis (Switzerland)) for psoriatic arthritis.

At the SMC's next scheduled meeting – due on 12 September 2016 – IHS expects SMC decisions on Kyprolis (carfilzomib, Amgen (US)) for multiple myeloma, Sprycel (dasatinib, BMS) for CLL, and Mekinist (trametinib) in combination with Tafinlar (dabrafenib) (Novartis) for advanced melanoma.

Imbruvica (ibrutinib) MCL

Johnson & Johnson (US)

1150/16

Yes

Treatment of adults with relapsed or refractory mantle cell lymphoma (MCL).

Approval was based on a Phase III trial in patients with relapsed or refractory MCL, in which Imbruvica significantly prolonged progression-free survival (PFS), the primary endpoint, compared with chemotherapy. The evaluation was conducted under end-of-life and ultra-orphan medicine criteria, and took account of feedback from a patient and clinician engagement (PACE) meeting, which stressed that there are limited effective treatment options for MCL, and that Imbruvica oral capsules are easy to administer, effective and well tolerated. A confidential discount was agreed under a patient access scheme (PAS) which improved cost-effectiveness.

Tresiba (insulin degludec)

Novo Nordisk (Denmark)

856/13

No

Treatment of diabetes mellitus in adults.

Tresiba is a long-acting insulin, administered by injection. Approval (on a second resubmission related to adults at least 18 years old only) was based on three Phase III studies in adults with type 1 diabetes mellitus, and five Phase III trials in adults with type 2 diabetes mellitus, which showed that Tresiba was non-inferior to other long-acting insulin analogues, as assessed by mean changes in glycosylated haemoglobin (HbA1c). The SMC ruled that it could offer an additional treatment option for diabetes patients, with extended duration of action and the ability to change the time of day administered, thus offering greater flexibility. Although Tresiba is also indicated for diabetes mellitus in adolescents and children over one year old, no SMC submission has been made, so it is not currently recommended for use in that indication by NHS Scotland.

Ayendi (diamorphine hydrochloride, intranasal spray)

Gilead Sciences (US)

1172/16

No

Treatment of severe nociceptive pain in children and adolescents in a hospital setting.

Ayendi was approved by the SMC under an abbreviated submission. Unlicensed intranasal diamorphine spray has been used by NHS Scotland for the treatment of severe pain in children in an emergency setting. Ayendi is a licensed preparation, and is now approved by the SMC for the treatment of acute severe nociceptive pain in children and adolescents in a hospital setting. The SMC advises that Ayendi should be administered in the emergency setting by practitioners experienced in the administration of opioids in children, and with appropriate monitoring.

Descovy (emtricitabine + tenofovir alafenamide)

Gilead Sciences (US)

1169/16

No

Use in combination with other antiretroviral agents for the treatment of adults and adolescents aged at least 12 years with body weight at least 35 kg, infected with HIV-1.

Descovy was approved by the SMC under an abbreviated submission. For HIV-1-infected adults in whom emtricitabine/tenofovir is an appropriate combination, Descovy (emtricitabine + tenofovir alafenamide) offers an alternative to Truvada (emtricitabine + tenofovir disoproxil) at no additional cost, and may also be used in patients from 12 years of age.

Edurant (rilpivirine hydrochloride)

Johnson & Johnson (US)

1168/16

No

Use in combination with other antiretroviral agents for the treatment of HIV-1 infection in antiretroviral-naïve patients aged 12–18 years, and older with a viral load of no more than 100,000 HIV-1 RNA copies/ml.

Edurant was approved by the SMC under an abbreviated submission. It is approved for use in combination with other antiretroviral agents in antiretroviral treatment-naive patients aged 12-18 years, or older, with a viral load of 100,000 HIV-1 RNA copies/ml or lower. It was previously approved by the SMC for this indication in adult HIV-1 patients only.

Praluent (alirocumab)

Sanofi (France)

1147/16

Yes

Treatment of adults with primary heterozygous familial hypercholesteroaemia (HeFH) or non-familial hypercholesterolaemia or mixed dyslipidaemia as an adjunct to diet, in combination with a statin, or statin plus other lipid-lowering therapies, in patients unable to reach low density lipoprotein-cholesterol (LDL-C) goals with the maximum tolerated dose of statin, or alone or in combination with other lipid-lowering therapies in patients who are statin-intolerant, or for whom a statin is contraindicated. SMC restriction: for specialist use only in patients at high cardiovascular (CV) risk: with HeFH and LDL-C at lesat 5.0 mM for primary prevention of CV events; with HeFH and LDL-C at least 3.5 mM, for secondary prevention of CV events; with previous CV events and LDL-C at least 4.0 mM; or with recurrent/polyvascular disease and LDL-C at least 3.5 mM.

Approval was based on a large Phase III programme in hypercholesterolaemia patients unable to reach lipid goals with available therapies, in which Praluent significantly reduced LDL-C from baseline to week 24 versus active and placebo comparators. The drug is administered by fortnightly injections. Incremental cost-effectiveness ratios (ICERs) were below GBP30,000 (USD39,011) per quality-adjusted life year (QALY) in all patient subgroups, except for the HeFH primary prevention group, where the ICER increased to GBP37,000 when the treatment benefit was reduced to five years. However, the SMC considered that the economic case for the drug was demonstrated. A PAS discount was agreed, which improved cost-effectiveness.

Imbruvica (ibrutinib) CLL

Johnson & Johnson (US)

1151/16

Yes

Treatment of adults with chronic lymphocytic leukaemia (CLL) who have received at least one prior therapy, or first-line in the presence of a 17p deletion or TP53 mutation in patients unsuitable for chemo-immunotherapy. SMC restriction: patients with 17p deletion or TP53 mutation who are unsuitable for chemo-immunotherapy.

Approval was based on the RESONATE open-label Phase III study in patients with relapsed or refractory CLL, where Imbruvica significantly increased PFS compared with an anti-CD20 antibody. For treatment-naive adults with a 17p deletion or TP53 mutation, the ICER was GBP40,942 with an agreed PAS taken into account. The evaluation was conducted under end-of-life and orphan medicine criteria, and took account of feedback from a patient and clinician engagement (PACE) meeting which highlighted that Imbruvica may delay progression and improve quality of life in patients for whom prognosis is poor and current treatment options are limited. A PAS discount was agreed, which improved cost-effectiveness.

Quinsair (levofloxacin inhaled)

Raptor Pharmaceuticals (US)

1162/16

Yes

Management of chronic pulmonary infections due to Pseudomonas aeruginosa in adults with cystic fibrosis. SMC restriction: for use as a third-line option after colistimethate sodium (first-line) and tobramycin (second-line).

Approval of Quinsair as a third-line treatment was based on a Phase III open-label trial in cystic fibrosis patients with chronic Pseudomonas aeruginosa airway infections. In the trial, Quinsair was non-inferior to inhaled tobramycin regarding change in lung function, as measured by forced expiratory volume in one second (FEV1) percent predicted. The SMC considered Quinsair to be an inhaled treatment which could be adminstered easily, improving the quality of life of cystic fibrosis patients with Pseudomonas airway infections. Quinsair was evaluated under an orphan equivalent process. A PAS was agreed, which improved cost-effectiveness.

Opdivo (nivolumab)

Bristol-Myers Squibb (US)

1120/16

Yes

As monotherapy for advanced unresectable or metastatic melanoma in adults. SMC restriction: for use only in patients previously untreated with ipilimumab.

Approval was based on a Phase III trial in patients with previously untreated advanced melanoma, and without a BRAF mutation, where Opdivo extended overall survival compared with palliative chemotherapy. In an ongoing open-label Phase III trial in advanced melanoma patients previously treated with an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) drug and/or a BRAF inhibitor, Opdivo extended overall response rate versus chemotherapy. The base-case economic analysis assumed that patients were treated for a maximum of two years. Opdivo met the criteria for evaluation under end-of-life and orphan medicine processes. Discussions at a PACE meeting highlighted that Opdivo can delay the progression of melanoma, and has different side-effects from some other medicines, increasing options for patients. A PAS was agreed, which improved cost-effectiveness.

Cosentyx (secukinumab)

Novartis (Switzerland)

1167/16

Yes

Use alone or in combination with methotrexate for the treatment of active psoriatic arthritis in adults with an inadequate response to previous disease-modifying antirheumatic drug (DMARD) therapy.

Approval was mostly based on the FUTURE 2 Phase III trial in patients with active psoriatic arthritis, where significantly more patients on Cosentyx achieved at least a 20% improvement in the ACR20 response at 24 weeks versus placebo. A PAS was agreed, which improved cost-effectiveness.

Respreeza (human alpha-1 proteinase inhibitor)

CSL Behring (Australia)

1157/16

No

Maintenance treatment to slow the progression of emphysema in adults with documented severe alpha-1-proteinase inhibitor (A1-PI) deficiency.

In trials, treatment with Respreeza for two years reduced the rate of lung density loss versus placebo. However, the SMC considered that there was a lack of "robust evidence" concerning the clinical relevance of this outcome, and that no improvements in pulmonary exacerbations, lung function or quality of life were demonstrated. The committee ruled that CSL Behring had not presented a sufficiently robust clnical or economic analysis, and that the cost of Repreeza in relation to its benefit did not justify NHS Scotland funding. The SMC took account of feedback from a PACE meeting.

Empliciti (elotuzumab)

Bristol-Myers Squibb (US)

1183/16

Treatment of multiple myeloma in combination with lenalidomide and dexamethasone in adults who have received at least one prior therapy

Non-submission

Portrazza (necitumumab)

Eli Lilly (US)

1184/16

Use in combination with gemcitabien and cisplatin chemotherapy for the treatment of adults with locally advanced or metastatic epidermal growth factor receptor (EGFR)-expressing squamous non-small-cell lung cancer (NSCLC) who have not received prior chemotherapy.

Non-submission