Scotland’s SMC OKs Drugs For Cancer & Plaque Psoriasis

The Scottish Medicines Consortium has OKd Keytruda, Decapeptyl, Yescarta and Skyrizi after patient access schemes were agreed that improved their cost-effectiveness. But Perjeta and Xtandi were rejected because the companies made no solid economic case for NHS funding.

The SMC has OKd four drugs as cost effective

The Scottish Medicines Consortium, Scotland’s health technology assessment body, has recommended the use of four innovative therapies, three of them for cancer indications. However, in its latest set of recommendations it also turned down two other drugs for cancer.

The three cancer therapies OKd by the SMC are Merck Sharp & Dohme Ltd.’s Keytruda (pembrolizumab) for metastatic non-squamous non-small cell lung cancer (NSCLC), Ipsen’s Decapeptyl (triptorelin acetate) for early stage breast cancer, and Gilead Sciences Inc.’s CAR-T therapy Yescarta (axicabtagene ciloleucel) for lymphoma. The Yescarta decision, which reverses an earlier rejection by the SMC, has been reported separately in the Pink Sheet. (Also see "Scottish HTA Reverses No For Yescarta" - Pink Sheet, 8 Oct, 2019.)

The fourth product to win a recommendation was AbbVie Inc.’s Skyrizi (risankizumab) for plaque psoriasis. All four therapies were OKd after the respective companies agreed patient access schemes (PASs) that included a confidential discount on the list price.

Alan MacDonald, the SMC’s chair, said Keytruda could “extend life expectancy giving patients the chance of some valuable extra time with their families in the context of this incurable illness,” and that patient groups and clinicians had made it known that Decapeptyl would be “a welcome additional treatment option for those with early stage breast cancer at high risk of recurrence.”

The decision on Skyrizi would be welcome given that additional treatment options are needed for plaque psoriasis in patients whose previous treatments have not worked, he said.

“The company’s evidence around Perjeta's clinical and economic benefits was not sufficient” – SMC

By contrast, the SMC turned down Roche’s Perjeta (pertuzumab) for early breast cancer at high risk of recurrence and Astellas Pharma Inc.’s Xtandi (enzalutamide) for early-stage prostate cancer.

MacDonald said the consortium was unable to accept Perjeta for this use because “the company’s evidence around its clinical and economic benefits was not sufficient.” In the case of Xtandi, the SMC cited “uncertainties in the company’s evidence about the benefits of using enzalutamide at this point in treatment.”

Keytruda

The SMC accepted Keytruda in combination with chemotherapy for the initial treatment of metastatic non-squamous NSCLC in adults whose tumors have no EGFR or ALK positive mutations. It said that the addition of pembrolizumab to pemetrexed and platinum chemotherapy “significantly improved progression-free survival and overall survival.”

However, it can only be used for up to two years in patients whose tumors produce either no or low levels of the PD-L1 protein, or where it has not been possible to measure the amount of PD-L1 produced.

MSD’s application was initially rejected in February this year, when the SMC said that the company’s justification of the treatment’s cost in relation to its health benefits “was not sufficient and in addition the company did not present a sufficiently robust economic analysis to gain acceptance by SMC.”

The consortium has now changed its mind, apparently after the company agreed a PAS that improved the drug’s cost effectiveness.

“After careful consideration, applying extra flexibility because pembrolizumab is a medicine for an end of life condition, and after receiving a confidential discount from the company, SMC was able to accept it as a possible treatment within NHS Scotland,” the consortium said.

Decapeptyl

Ipsen’s Decapeptyl was OKd by the SMC together with tamoxifen or an aromatase inhibitor for the treatment of endocrine-responsive early-stage breast cancer at high risk of occurrence in pre-menopausal women who have had surgery and chemotherapy. This decision also took account of a PAS with a confidential discount that improves the therapy’s cost effectiveness.

According to the SMC, there were some weaknesses in the evidence base used by the company to support the assumption of clinical equivalence with other treatments, and Ipsen also excluded monitoring costs from the economic analysis, “on the basis that these are likely to be similar between treatments.”  Despite these issues, “the economic case was considered demonstrated,” the consortium commented.

Ipsen assumed that there would be 121 patients eligible for treatment in Scotland in the first year, rising to 528 by year five.

Skyrizi

Skyrizi was accepted by the SMC for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy, but only those who have not responded to, or are unable to take, standard therapies like ciclosporin, methotrexate and phototherapy.

The consortium noted that psoriasis is caused by an over-active immune system. “IL-23 is a protein involved in the immune system that is over-active in patients with plaque psoriasis. Risankizumab binds to and blocks IL-23, which decreases the amount of inflammation and symptoms of plaque psoriasis.”

Skyrizi would offer “another treatment option that could lead to an improved quality of life for some people" – SMC

AbbVie had originally provided comparisons against three other drugs, adalimumab, ustekinumab and secukinumab, on the basis of previous market share data and a guideline from the British Association of Dermatologists stating that these are the most commonly chosen first-line biologics.

“However, SMC clinical expert input suggested that risankizumab is initially likely to be used as a later line treatment, therefore additional comparisons against more recently available treatments (guselkumab, brodalumab and ixekizumab) were provided upon request,” the consortium added.

It concluded that Skyrizi would offer “another treatment option that could lead to an improved quality of life for some people, allowing them to experience a life that is not blighted and restricted by the impact of the physical and mental aspects of psoriasis.”

Again, the SMC decided to recommend funding for Skyrizi after the company agreed a PAS with a discount that improves its cost-effectiveness.

No Luck For Perjeta Or Xtandi

Roche had submitted Perjeta as an adjuvant treatment for early-stage HER2-positive breast cancer at high risk of recurrence.

The SMC considered the product’s benefits in the context of decision modifiers that can be used in the case of high cost-effectiveness ratios, and agreed that as pertuzumab is an “ orphan equivalent” medicine, it could accept greater uncertainty in the economic case.

However, it concluded that the company did not present a “sufficiently robust clinical or economic analysis” to show that pertuzumab “offers value for money to NHSScotland.” This, it said, was “despite applying extra flexibility as pertuzumab is a medicine for a rare condition.”

Xtandi had been put before the SMC as a treatment for castration-resistant prostate cancer that is not metastatic but is at high risk of spreading to other parts of the body. The SMC observed that in a Phase III study, enzalutamide was superior to placebo for metastasis-free survival. “High-risk was defined as prostate specific antigen (PSA) doubling time ≤10 months and PSA ≥2 nanograms/mL. Both groups received on-going androgen-deprivation therapy or had undergone bilateral orchiectomy. Overall survival data are immature,” the consortium said.

As with Perjeta, the SMC noted that greater economic uncertainty could be accepted as Xtandi was an orphan equivalent drug, but in the end it concluded that Astellas’s evidence was not sufficient to show value for money.