Welcome to your weekly digest of approaching regulatory and clinical readouts. By September 21 Glaxosmithkline’s triple combination for COPD in a single inhaler will go before the FDA. Payer support will likely be the bigger battle as generics of the individual components are on the horizon.
Also phase III results of Xtandi in earlier stages of prostate cancer are due in the fourth quarter. A recent protocol change sped up the readout by nearly two years, cementing Xtandi’s dominant position in this overall indication.
Glaxosmithkline’s combination of fluticasone furoate, umeclidinium and vilanterol trifenatate (FF/UMEC/VI), is a steroid, LAMA and LABA combination. Also known as its closed triple it could be the first such product to reach the US if approved by the end of September.
The idea is that it will offer a once-daily treatment in a single Ellipta inhaler as an option for patients with advanced disease. These patients often need multiple therapies that are delivered via two or more inhalers.
Others pursuing a triple combination in COPD are Astrazeneca with PT010 in phase III, while Chiesi‘s Trimbow is ahead in Europe with a recent approval.
GSK’s US filing was based on the Fulfil phase III trial, a 1,800-patient test in which FF/UMEC/VI showed superiority over the LABA/steroid combination Symbicort in lung function and health-related quality of life measures (Can Glaxo’s COPD triple play a solo act?, November 21, 2016).
A second, larger phase III trial called Impact tests whether treatment with FF/UMEC/VI is better at preventing exacerbations of COPD than Breo or Anoro Ellipta, a LABA/steroid and LABA/LAMA respectively. This trial is due to read out in the fourth quarter.
However, neither trial determines whether the ‘closed’ combination is better than an open combination of a LABA/steroid plus LAMA monotherapy, such as Glaxo’s Advair plus Boehringer’s Spiriva. The latter is due to lose patent protection next year while Advair’s has gone already. Sales are set to drop from nearly $1.7bn this year to $689m by 2022 in COPD, according to consensus from EvaluatePharma; however, directly substitutable generics have run into problems with the FDA (Snippet roundup: Sighs of relief for Astra and Glaxo, May 12, 2017).
For GSK’s closed triple 2022 sales are expected to reach $780m, making it the fourth biggest seller by 2022 (see table). Theravance and Innoviva have a profit share.
However, without a superiority claim over the three separate components it could be very difficult to persuade pharmacy benefit managers that once-daily doses of a closed triple are worth a premium price versus one puff of Spiriva and two of Advair, particularly as generics enter.
|Top 5 COPD products by 2022|
|Annual indication sales ($m)|
|Product||Generic name||Company||2016||2018||2020||2022||Indication status|
|Spiriva||tiotropium bromide||Boehringer Ingelheim||3,314||3,183||3,156||3,129||Marketed|
|Utibron Neohaler||glycopyrrolate; indacaterol maleate||Novartis||363||517||638||718||Marketed|
The phase III Prosper trial is testing Astellas’s Xtandi in patients with non-metastatic castration-resistant prostate cancer versus placebo. 160mg Xtandi is given once daily and the primary measure is metastasis-free survival after 16 weeks. Secondary endpoints include overall survival, and data are due by the fourth quarter.
In June Astellas and collaborator Pfizer reduced the enrolment size from 1,560 to approximately 1,440 patients. The main purpose was to revise the plan for the analyses of the primary and several secondary endpoints, which according to Evercore ISI analysts allowed the metastasis-free survival endpoint to be decoupled from the overall survival measure. This meant that the trial maintained the same power while reducing the overall number of patients. It's unclear how the FDA might view the change in analyses, originally the study was due to report in 2019.
Xtandi is approved for the treatment of men with metastatic castration-resistant prostate cancer, either before or after the use of docetaxel chemotherapy. Its approved uses exactly mirror those of Johnson & Johnson’s Zytiga. Arguments whether to use Xtandi or Zytiga in these patients have focused on marginal differences in efficacy coupled with Zytiga’s requirement for co-administration with prednisolone.
The key advantage of the Prosper study is that it allows use of Xtandi ahead of Zytiga and the recent study amendment could mean it sneaks ahead of competition in the same setting. Data are due from the Spartan study of J&J’s follow-up agent apalutamide, which had a primary completion date in June so could also report shortly, and the Aramis study of Bayer’s androgen receptor blocker BAY1841788, due to complete next year.
According to consensus from EvaluatePharma Xtandi will lead the prostate cancer market by 2022 with $3.8bn, still way ahead of the competition (see table).
|Top 5 prostate cancer products by 2022|
|Annual indication sales ($m)|
|Apalutamide||Johnson & Johnson||-||83||563||1,108||Phase III|
|Zytiga||Johnson & Johnson||2,260||1,983||1,120||759||Marketed|