26 April 2018 - Analysis of the outcomes from the March 2018 PBAC meeting reveals some interesting findings.

Company

• The companies that fared well are AstraZeneca (3 submissions, 4 outcomes, 3 recommendations) and Amgen (3 submissions, 3 outcomes and 3 recommendations)
  
• The compared that fared poorly are Celgene (2 submissions, 2 outcomes, 2 rejections) and Janssen-Cilag (3 submissions, 4 outcomes, 3 rejections)
  

Technology

• The PBAC recommended the PBS listing of the first gene therapy, nusinersen sodium (Spinraza). The PBAC recommended tits listing for Type 1, Type II and Type III spinal muscular atrophy (SMA) despite the fact that the resubmission only sought a listing for patients with Type 1 SMA.  The initial submission sought a listing for Types I, II & III SMA.
  
• Baricitinib (Olumiant), a Janus kinase 1 & 2 inhibitor, was recommended for listing on the PBS for certain patients with severe active rheumatoid arthritis on a cost-minimisation basis against the least costly biological disease modifying anti-rheumatic drug (bDMARD). It is interesting to note that it was not recommended (on a cost-minimisation basis) against its PBS listed pharmacological analogue tofacitinib citrate (Xeljanz). The PBAC recommended the listing of the 2 mg & 4 mg tablets. Baricitinib is not yet registered in the US; an FDA Advisory Committee recently recommended the approval of the 2 mg but not the 4 mg tablets.
• A number of medicines were recommended on the proviso that a price reduction is required to achieve acceptable cost-effectiveness: cetuximab (Erbitux) for patients with head and neck cancer, Meningococcal Groups A, C, W135 & Y conjugate vaccine (Nimenrix) for the prevention of invasive meningococcal disease in infants, nusinersen sodium (Spinraza) for spinal muscular atrophy, olaparib (Lynparza) for patients with ovarian cancer, omalizumab (Xolair) for patients with urticaria, palbociclib (Ibrance) for patients with breast cancer, ramucirumab (Cyramza) for patients with gastro-oesophageal cancer and ribociclib succinate (Kisqali) for patients with breast cancer.  This appears to be a new development.
• Palbociclib (Ibrance) and ribociclib succinate (Kisqali) were recommended for use by certain patients with breast cancer after three submissions.  This appears to be the norm; on average it takes approximately three submissions to obtain a PBAC recommendation for a new cancer medicine.  There are or course, some exceptions; the PBAC recommended the listing of ramucirumab (Cyramza) at the Match 2018 meeting after just one (major) submission.
• The PBAC's consideration of the submission for guselkumab (Tremfya) is puzzling. The PBAC did not recommend the listing of guselkumab, an interleukin 23 receptor antagonist, for the treatment of severe chronic plaque psoriasis as it considered that ustekinumab, an interleukin 12 and 23 receptor antagonist, was an inappropriate choice as a main comparator. The PBAC considered that any of the biologic agents listed on the PBS for plaque psoriasis may be replaced by guselkumab and hence be a relevant comparator. The PBAC agreed with ESC that infliximab (tumour necrosis factor antagonist) was a relevant comparator, and considered that the indirect comparison presented in the Pre-PBAC response would need to be evaluated as part of a major submission. The PBAC noted the information referenced by ESC that suggested ixekizumab (interleukin 17 receptor antagonist) may be the most effective of the PBS listed biologics. Given this, the PBAC considered that a comparison versus ixekizumab would also be informative.
• The folks at Celgene and Servier must be left shell shocked after the submissions for apremilast (Otezla) and trifluridine with tipiracil hydrochloride (Lonsulf) were rejected yet again.  There have been five submissions for both medicines; apremilast has been rejected four times (and deferred once); trifluridine with tipiracil hydrochloride has been rejected five times. Both were rejected due to 'unacceptable cost-effectiveness'; one could ask why they weren't recommended on the proviso of a further price reduction in order to achieve acceptable cost-effectiveness. One thing is clear; the PBAC is not a fan of the use of a risk share agreement to circumvent a price reduction.
• Hitting an MCID does not guarantee the acceptance of a clinical claim. The PBAC noted Merck Serono's arguments in the minor submission for cladribine (Mavenclad) on the use of the minimal clinically important differences (MCID) used in the ocrelizumab submission for use by patients with relapsing-remitting multiple sclerosis in assessing the efficacy of cladribine. The PBAC recalled that it recommended ocrelizumab based on the totality of the evidence presented in that submission, and not on the basis of the proposed MCID. The PBAC noted that the minor resubmission did not address its concerns regarding the uncertainty in the non-inferior efficacy between cladribine and fingolimod hydrochloride over four years, or uncertainty in the non-inferior safety between cladribine and fingolimod hydrochloride. The PBAC therefore considered that the uncertainty in the non-inferior efficacy claim over two and four years, and non-inferior safety claim between cladribine and fingolimod hydrochloride, remained. While Mavenclad is better than Movectro, Merck Serono is yet to convince the PBAC that cladribine is not inferior to fingolimod hydrochloride.