Approval decisions for oncology drugs feature heavily in May and the coming months. Two Parp inhibitors will take the spotlight in prostate cancer, with Clovis’s Rubraca due a decision in patients with BRCA1/2 mutations by May 15, and Astrazeneca’s Lynparza, which has been filed in the broader setting of homologous recombination repair gene mutations, and has a second quarter date.
Last week the latest cut of Lynparza’s Profound study found a survival benefit in patients with BRCA1/2 or ATM gene mutations, but no efficacy data were released from carriers of other mutation types. The question will be how broad a label the FDA might give the drug.
Lynparza is filed in the earlier second-line setting, versus Rubraca’s third, and there is little evidence to support retreating patients with a Parp inhibitor. Sales by indication data from EvaluatePharma gives Astra’s therapy the lead in prostate cancer with $1.3bn Lynparza sales forecast for 2026, versus Rubraca’s $347m.
Another decision for Lynparza, also due in the second quarter, is in ovarian cancer, based on the results of the Paola-1 study. The investigator-sponsored study tested the anti-VEGF antibody Avastin plus Lynparza, and recruited patients regardless of mutation status.
Data released at last year’s Esmo showed that progression-free survival was significantly extended, although the result was clearly driven by patients with homologous recombinant deficiency (HRD) – in the subgroup of those without evidence of HRD the hazard ratio dropped to an unimpressive 0.92.
The big question is whether Paola-1 will allow Lynparza to gain approval to treat all front-line ovarian cancer, regardless of HRD status, though presumably any label would restrict its use to Avastin combination therapy.
Astrazeneca will now have to contend with GSK’s own parp, Zejula, which as a single agent gained US approval just a few days ago in ovarian cancer regardless of biomarker status. Zejula’s decision was based on the Prima study, in a group described as "HRD-proficient", essentially negative, in which the hazard ratio was 0.68, or a 32% reduction in the risk of progression.
Meanwhile Bristol Myers Squibb will find out whether Opdivo plus Yervoy will get the green light in first-line lung cancer. The latest filing is based on a pooled result of part one of the Checkmate-227 trial. Bristol had earlier controversially claimed a progression-free survival benefit in patients with high tumour mutation burden after abandoning its original statistical analysis plan and creating a whole new cohort of patients, but this filing plan was abandoned.
Bristol is doubling its chances in first-line NSCLC with a Pdufa set for August based on the Checkmate-9LA study, this time concerning Opdivo plus Yervoy and chemotherapy. Merck’s Keytruda is already on the market first line in combination with chemotherapy, and according to consensus from EvaluatePharma Keytruda forecasts sit at $4.4bn by 2026 versus Opdivo’s $3.7bn.
|Supplementary and other notable approval decisions in May|
|Product||Company||Indication (clinical trial)||Date|
|Rubraca||Clovis||BRCA1/2-mutant recurrent mCRPC (Triton3)||May 15|
|Opdivo + Yervoy||Bristol Myers Squibb||1L NSCLC without chemo (Checkmate-227)||May 15|
|Dupixent||Sanofi||Atopic dermatitis in children aged 6 to 11 years||May 26|
|Subcutaneous Darzalex||J&J||Multiple myeloma (Columba)||Q2|
|Farxiga||Astrazeneca||Reduce the risk of CV death or the worsening of heart failure in adults with HFrEF with and without type 2 diabetes (Dapa-HF)||Q2|
|Lynparza + Avastin||Astrazeneca||Advanced ovarian cancer maintenance with Avastin (Paola-1)||Q2|
|Lynparza||Astrazeneca||mCRPC and germline or somatic HRR mutations (Profound)||Q2|
|Source: EvaluatePharma & company releases.|
Oncology aside, Astrazeneca’s SGLT2 inhibitor Farxiga, already marketed for type 2 diabetes, looks set to be approved for heart failure based on the Dapa-HF trial.
Overall, patients receiving Farxiga plus standard of care had a 26% reduction in the primary endpoint – cardiovascular death, hospitalisation for heart failure, or an urgent heart failure visit – versus those receiving standard of care alone. The difference was highly statistically significant, with a p value of less than 0.0001.
Astra has a chance to get a head start against the competition − Lilly and Boehringer’s SGLT2 inhibitor Jardiance is the biggest threat. Jardiance’s Emperor-Reduced study, analogous to Dapa-HF, has a primary completion date in June.
Jardiance is set to be the biggest in the class in 2026, according to EvaluatePharma sellside consensus, with forecast sales that year of $4.2bn versus Farxiga’s $3.2bn. Neither of these estimates includes heart failure, so presumably there could be a big upside if the drugs can make a mark here.
Lastly Abbvie’s Orilissa, already on the market for the management of pain associated with endometriosis, has a decision due in uterine fibroids. If approved the GnRH antagonist would be ahead of competition from Myovant and Obseva, and cross trial comparisons of the three puts Abbvie’s product out on top in terms of placebo-adjusted response rate.
|Notable first-time US approval decisions due in May|
|Project||Company||PDUFA date||2026e sales ($m)||Evaluate Vantage note/story link|
|Naloxone Nasal Spray||Insys Therapeutics||Est May||-||-|
|Ayvakit||Blueprint Medicines||May 14||1,119*||Supporting Voyager trial in 4L GIST failed so approval very unlikely.|
|Dasotraline/SEP-225289||Sumitomo Dainippon Pharma||May 14||124||Filed in binge eating disorder, received a CRL in ADHD.|
|Apomorphine sublingual film (APL-130277)||Sunovion/Aquestive Therapeutics||May 21 (resubmission)||155||Received CRL last year, filed to treat off episodes in Parkinson's disease.|
|Phexxi (Amphora vaginal pH regulator)||Evofem biosciences||May 25 (resubmission)||541||Previous CRL.|
|Adstiladrin/nadofaragene firadenovec||Ferring/Fergene||Est May 29||-||Filed in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC); Merck's Keytruda received approval in this setting in January.|
|Aximris XR (oxycodone extended-release tablets)||Intellipharmaceutics International||Q2 (resubmission)||43||Negative adcom in January, 24 to 2 voted against approval.|
(538 in uterine fibroids)
|*Forecasts made before Voyager failure. Source: EvaluatePharma & company releases.|