Merck looks for a return on its Lynparza investment

Merck & Co has sunk billions into Lynparza, but its Keytruda combo plan, which it is funding solely, just got off to a rocky start.

When Merck & Co bought into Astrazeneca’s Parp inhibitor Lynparza in 2017 it also kicked off a series of combo pivotal studies designed to broaden the reach of Keytruda. This clinical work alone is thought to be costing Merck $1.2bn, Evaluate Pharma data calculate.

The figures are important because several of these trials, including in ovarian, lung and breast cancers, might be reading out this year. Unfortunately for Merck this effort has got off to an inauspicious start, with the first pivotal combo study, Keylynk-010, in prostate cancer, being halted after an interim analysis found it to be futile.

Keylynk-010 had tested Keytruda plus Lynparza in castrate-resistant prostate cancer patients who had already failed chemotherapy and either Zytiga or Xtandi, pitting the combo against Xtandi or Zytiga in the two respective populations. A data-monitoring board this week recommended scrapping it after seeing no benefit in either of its co-primary endpoints, radiographic progression-free and overall survival.

More on the way

The study was the first of several in the Keylynk programme to yield a result.

Next up are three trials that will add Lynparza as maintenance therapy while patients are still in response to front-line Keytruda plus chemo, in cancers where Keytruda plus chemo is already approved: ovarian cancer (Keylynk-001), squamous NSCLC (Keylynk-008) and triple-negative breast cancer (Keylynk-009). Interestingly, the last study recruits all-comers even though Keytruda’s front-line label mandates ≥10% PD-L1 expression.

Merck's solely funded Lynparza programme
Trial Setting Active Control Primary Data due Estimated trial cost ($m)
Keylynk-010 3rd-line castrate-resistant prostate cancer Keytruda + Lynparza Zytiga or Xtandi OS & rPFS Failed 123
Keylynk-001 1st-line (maintenance) Brca W/T ovarian cancer Lynparza (after 1st-line Keytruda + chemo) Placebo PFS Imminent* 247
Keylynk-008 1st-line (maintenance) squamous NSCLC Keytruda + Lynparza (after 1st-line Keytruda + chemo) Keytruda + chemo OS & PFS Dec 2022* 138
Keylynk-009 1st-line (maintenance) triple-negative breast cancer Keytruda + Lynparza (after 1st-line Keytruda + chemo) Keytruda + chemo OS & PFS Dec 2022* 214
Keylynk-012 1st-line (maintenance) stage III NSCLC Keytruda + Lynparza (after 1st-line Keytruda + CRT) Imfinzi or Keytruda OS & PFS Apr 2023* 159
Keylynk-007** ≥2nd-line HRRm/HRD+ve cancers Keytruda + Lynparza None ORR Jun 2024 51
Keylynk-006 1st-line (maintenance) non-squamous NSCLC Keytruda + Lynparza (after 1st-line Keytruda + chemo) Keytruda + chemo OS & PFS Aug 2024 188
Keylynk-013 1st-line (maintenance) SCLC Keytruda + Lynparza (after 1st-line Keytruda + CRT) Placebo OS & PFS Oct 2027 120
CRT=chemo-radiotherapy; HRD=homologous recombination deficiency; HRRm=homologous recombination repair mutant; *Company/analyst expectation; all others per; **Phase 2; all others are phase 3. Source: Evaluate Omnium. 

Under the companies’ 2017 agreement Merck paid Astra $1.6bn up front, plus $750m for “certain licence options”, for a 50% share of gross profits generated by Lynparza. Monotherapy Lynparza trial costs were to be shared, while Astra took on the burden of funding any studies combining Lynparza with  Imfinzi.

Those in which the Parp inhibitor was being combined with Keytruda, however, were to be the sole responsibility of Merck. According to Evaluate Omnium's estimates, the eight Keylynk trials combined amount to a cost of $1.2bn, including $123m for the failed ‘010 study.

As a brand Lynparza has sold a cumulative $6bn since the 2017 deal, and is expected to bring in $5.6bn in 2026 alone. Even a conservative 85% gross profit margin suggests that Merck might already be close to recouping its up-front fee. As for the Keytruda combo studies, however, the jury is still out.

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