Upcoming events: Dalvance data and US decisions for Lynparza and Zerbaxa

Welcome to your weekly digest of approaching regulatory and clinical readouts. An FDA decision is expected by January 3 for AstraZeneca’s Lynparza in ovarian cancer. However, with a negative advisory panel behind, if it regulators chose to wait for the results of phase III trials approval could be delayed until at least 2016.

Meanwhile, data from Actavis’s Dalvance as a single-dose regimen are expected early next year. The antibiotic is on the market in the US in a form that has to be infused in two doses a week apart, so improved dosing could help its position. Lastly, US regulatory action on Cubist’s antibiotic Zerbaxa is expected by December 21, and a negative outcome would provide a further embarrassment for the group's proposed acquirer, Merck & Co.

AstraZeneca: Lynparza

In June an FDA panel voted 11-2 against accelerated approval of Lynparza, known generically as olaparib, pending data from two phase III trials called Solo-1 and Solo-2. The filing was based on a failed phase II study in which a predefined subgroup, identified using a retrospective biomarker, found a significant progression-free survival benefit in ovarian cancer patients with the BRCA mutation (Olaparib slapdown undermines Astra’s hype, June 26, 2014).

The panel was not convinced by either Lynparza’s safety or its real benefit. Data from the phase III trials are not expected until late 2015/early 2016. Solo-1 tests Lynparza after first-line platinum chemotherapy, while Solo-2 is after complete or partial response to platinum chemo.

The PDUFA date was originally set for October; however, in July the company submitted a major amendment to the US regulator and the decision was delayed until January. AstraZeneca executives have issued bullish sales projections on the project and have stated publically that they are confident on US approval, so a negative decision would be viewed as a set back.

Over in Europe the path to approval has been a completely different story, with the CHMP issuing a positive opinion in October. The PARP inhibitor is to be used as a monotherapy for maintenance treatment of adults with BRCA-mutated platinum-sensitive relapsed ovarian cancer.

According to consensus from EvaluatePharma worldwide 2020 sales are forecast to reach $651m, but the range in forecasts is considerable, from $351m to $1bn.

Actavis: Dalvance

Dalvance (dalbavancin) was approved in the US in May as an intravenous antibiotic to treat patients with acute bacterial skin and skin structure infections (ABSSIs) caused by Gram-positive bacteria. It was the first QIDP-designated product to reach the US market (FDA antibiotics programme yields first approval in Durata’s Dalvance, May 27, 2014).

It is given as a two-dose regimen at 1,000mg followed a week later by 500mg. Intravenous administration has its obvious drawbacks, while the regimen raises concerns that patients would not return for the second dose, thereby contributing to the very problem of antibiotic resistance that prompted its development.

In April the company started a trial comparing the efficacy of a single 1,500mg dose against the current two-dose regimen in patients with known or suspected Gram-positive ABSSI. This seeks to recruit 698 patients, and measures the percentage of patients who demonstrate a clinical response at 48-72 hours after initiation of therapy. A supplemental NDA filing for the single dose is expected by mid-2015.

With a single-regimen in the bag Dalvance would be better placed to compete. The Medicines Company’s Orbactiv was approved in the US in August, also with QIDP designation. Although its intravenous infusion takes longer at over 3 hours, this is given as a single 1,200mg dose, while Cubist’s Sivextro, also single-dosed, can either be taken orally or intravenously. 

JP Morgan analysts forecast $204m of Dalvance sales by 2020. According to consensus from EvaluatePharma Orbactiv will lead the market in 2020 with forecast sales of $309m, with Sivextro at $216m.

Cubist Pharmaceuticals: Zerbaxa

Zerbaxa, previously known as CXA-201, works on Gram-negative bacteria and was filed to treat intra-abdominal and urinary tract infections. A US decision is expected by December 21 and will be eagerly watched by Merck investors since this week’s takeover bid for Cubist (Cubist patent loss means buyer’s remorse for Merck, December 9, 2014).

Zerbaxa is a combination of the beta-lactamase inhibitor tazobactam and ceftolozane, a novel cephalosporin. It also has QIDP designation. Last December it generated phase III data showing it to be non-inferior to Merrem in curing complicated intra-abdominal infections, and was subsequently filed for US approval; an EU decision is expected during the second half of 2015.

News that Cubist lost its Cubicin patent litigation against Hospira has renewed interest in Zerbaxa. With 2020 forecasts hitting $733m, according to EvaluatePharma, Merck needs Zerbaxa to deliver the goods.

Product Study Trial ID
Lynparza (Phase II)
Solo-1
Solo-2
NCT00753545
NCT01844986
NCT01874353
Dalvance (Single vs two dose regimen) NCT02127970 
Zerbaxa (Zerbaxa vs Merrem) NCT01445678

To contact the writer of this story email Joanne Fagg in London at joannef@epvantage.com or follow @JoEPVantage on Twitter

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