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38924711000001103

New Medicines

PiqrayHR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after endocrine monotherapy

Information

Piqray
New molecular entity
Novartis
Novartis

Development and Regulatory status

Launched
Launched
Launched
September 2020
Sep 20Launched in the UK. Price: 50mg x 28 and 200mg x 28=£4082.14; 150mg x 56=£4082.14; 200mg x, 28=£4082.14 [16].
May 20Recommended for EU approval by CHMP - the full indication is "in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)‑negative, locally advanced or metastatic breast cancer with a PIK3CA mutation after disease progression following endocrine therapy as monotherapy." It is proposed that the medicine be prescribed by physicians experienced in the use of cancer treatments. [15]
May 19The FDA also approved the companion diagnostic test, therascreen PIK3CA RGQ PCR Kit, to detect the PIK3CA mutation in a tissue and/or a liquid biopsy. Patients who are negative by the therascreen test using the liquid biopsy should undergo tumour biopsy for PIK3CA mutation testing. Novartis has already launched Piqray with a list price of $15,500 for a 28-day supply [14].
May 19US FDA approved alpelisib in combination with fulvestrant (and its companion diagnostic test) for treatment of postmenopausal women, and men, with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), PIK3CA-mutated, advanced or metastatic breast cancer [13].
Feb 19Is also pre-registration in the US [11].
Feb 19Filed in EU [10].
Dec 17Filings planned for 2018 [6].
Mar 17Novartis remains on course to file in 2019 [5].
Dec 15Filings planned for 2019 [1].

Category

Phosphoinositide 3-kinase (P13K) alfa inhibitor
Approximately 80% of breast cancers in postmenopausal women are HR+. Approx 70–80% of people with metastatic breast cancer have HER2- tumours, of which about 50% will also be HR+. Both HR+ and HER2- breast cancers are associated with a better prognosis than HR- and HER2+ disease. PIK3CA mutations account for 40% of all HR+/HER2- breast cancer cases and are associated with poor disease prognosis [3,14].
HR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after endocrine monotherapy
Oral

Further information

Yes

Trial or other data

May 19Results of PIII SOLAR-1 RCT (n=572; NCT02437318) are published; at a median follow-up of 20 months, treatment with alpelisib, in combination with fulvestrant (FV) prolonged progression-free survival vs. FV in patients with PIK3CA-mutated cancer (11.0 vs. 5.7 months; HR 0.65; 95% CI,0.50-0.85; p<0.001) [12].
Oct 18Details of positive data from SOLAR-1 (n=572) posted by company. In HR+ advanced breast cancer pts with a PIK3CA mutation, progression free survival (PFS) was 11 months for alpelisib plus fulvestrant vs. 5.7 months for fulvestrant alone. The objective response rate (ORR) showed a reduction in tumour size of ~36% vs. 16% on fulvestrant alone but the PFS improvement was not seen in patients without the PIK3CA mutation. The most common all-grade adverse effects were hyperglycemia (64% vs 10%), diarrhoea (58% vs. 16%), nausea (45% vs. 22%), decreased appetite (36% vs. 11%) and rash (36% vs. 6%). Hyperglycemia was the most common grade 3/4 events (37% against <1%) [8].
Oct 18Novartis initiates an expanded access study to allow access to alpelisib for eligible patients with hormone receptor positive, advanced or metastatic breast cancer harboring a PIK3CA mutation (NCT03706573) [9].
Aug 18SOLAR-1 study meets it´s primary endpoint showing an improvement in progression free survival [7].
Dec 16NCT02437318 initial results due July 2019 [4].
Jul 15PIII SOLAR-1 study (NCT02437318) to determine whether treatment with alpelisib plus fulvestrant prolongs progression-free survival compared to fulvestrant and placebo in men and postmenopausal women with hormone receptor positive (HR+), HER2-negative advanced breast cancer, who received prior treatment with an Aromatase Inhibitor either as (neo)adjuvant or for advanced disease starts. 820 adults will be recruited in the US, Austria, Belgium, Canada, Czech Republic, France, Germany, Greece, Hong Kong, Hungary, Israel, Italy, Japan, Republic of Korea, Lebanon, Netherlands, Spain, Sweden, Taiwan & Thailand. Collection of primary outcome data should complete Jul 19 [2].

Evidence based evaluations

Piqray HR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after CDK-4/6 inhibitor plus an aromatase inhibitor

Information

Piqray
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Phosphoinositide 3-kinase (PI3K) alfa inhibitor
Approximately 80% of breast cancers in postmenopausal women are HR+. Approx 70–80% of people with metastatic breast cancer have HER2- tumours, of which about 50% will also be HR+. Both HR+ and HER2- breast cancers are associated with a better prognosis than HR- and HER2+ disease. PIK3CA mutations account for 40% of all HR+/HER2- breast cancer cases and are associated with poor disease prognosis [1,2].
HR-positive, HER2-negative, PIK3CA-mutated breast cancer - second-line with fulvestrant after CDK-4/6 inhibitor plus an aromatase inhibitor
Oral

Further information

Yes

Piqray Platinum refractory or resistant, BRCA1/2 wild type ovarian cancer - second-line plus, with olaparib

Information

Piqray
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

Phosphoinositide 3-kinase (PI3K) alfa inhibitor , dosed at 200mg once daily. Olaparib given orally as 200mg twice daily.
There are around 7,400 new ovarian cancer cases in the UK every year. Incidence rates for ovarian cancer have been projected to rise by 15% in the UK between 2014 and 2035, to 32 cases per 100,000 females by 2035 [1].
Platinum refractory or resistant, BRCA1/2 wild type ovarian cancer - second-line plus, with olaparib
Oral

Piqray Advanced triple negative breast cancer, with a PIK3CA mutation - in combination with Abraxane

Information

Piqray
Licence extension / variation
Novartis
Novartis

Development and Regulatory status

Phase III Clinical Trials
Phase III Clinical Trials
Phase III Clinical Trials

Category

Phosphoinositide 3-kinase (PI3K) alfa inhibitor. Dosed 300 mg once daily. Abraxane dosed at 100 mg/m² by IV infusion on days 1, 8 and 15 of a 28-day cycle.
There are around 55,200 new breast cancer cases in the UK every year. Around 15 out of every 100 breast cancers (15%) are triple negative [1].
Advanced triple negative breast cancer, with a PIK3CA mutation - in combination with Abraxane
Oral

Information

Vijoice
New formulation
Novartis
Novartis

Development and Regulatory status

None
Phase II Clinical Trials
Approved (Licensed)
Apr 22FDA approves Vijoice (alpelisib) to treat PIK3CA-related overgrowth spectrum (PROS) for patients aged 2 years and older with a severe form of the disorder that requires systemic therapy, the first drug specifically approved for the condition [8].
Feb 22Currently pre-registration in the US [7].
Dec 21Approval for PROS expected by 2026 [5].

Category

An α-specific class I PI3Kα inhibitor.
PROS is a group of rare disorders that cause overgrowth of parts of the body due to mutations in the PI3KCA gene. Signs and symptoms of PROS depend on the specific disorder present. Although reported rates of individual PROS disorders are low or unknown, the spectrum collectively could represent a more significant patient number, with an estimated prevalence of 14 people per million [1,2].
PIK3CA-related growth spectrum (PROS) in adults and children aged 2 years and older
Oral

Trial or other data

Jan 22Prospective interventional PII multi center study, open label, preceded by a retrospective non-interventional period, to assess the long-term safety and efficacy of alpelisib, in pediatric and adult participants with PROS starts (NCT04980833). 50 patients aged 2 years and older will be enrolled in France. Primary outcome (prospective period only) is proportion of participants with new or worsening grade ≥3 treatment emergent adverse events; collection of these data is due to complete Jul 27 [6].
Dec 21Recruitment continues in PII study (NCT04589650) [4].
Jun 21PII study (NCT04589650) is recruiting [3].
Apr 21PII study to assess the efficacy, safety and pharmacokinetics of alpelisib in pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS) starts (NCT04589650). This study consists of a screening period of up to 42 days, core period of 24 weeks, extension period of 23 weeks and long-term extension period of up to approximately 4 years. The study will enroll adult participants (Group 1), 6-17 years old pediatric participants (Group 2), and an exploratory set of 2-5 years old pediatric participants (Group 3). At study start, only the participants of Group 1 and Group 2 will be enrolled. 150 patients will be enrolled in the US, Norway and Spain. Primary outcome is response defined by achieving at least 20% reduction from baseline in the sum of target lesion volumes (1 to 3 lesions, assessed by MRI by a blinded independent review committee (BIRC)) at Week 24, provided that none of the individual target lesions has ≥ 20% increase from baseline and in absence of progression of non-target lesions and without new lesions; collection of these data is due to complete Mar 23 [3].