dm+d

Unassigned

New Medicines

NuzyraModerate to severe community-acquired pneumonia in adults

Information

Nuzyra
New molecular entity
Paratek
Paratek

Development and Regulatory status

Filing withdrawn
Phase III Clinical Trials
Launched
Jun 21FDA approves supplemental New Drug Application (sNDA) for the oral-only dosing regimen for CABP (involves an initial dose of 300 mg twice on day one and 300 mg once daily thereafter for a total of 7 to 14 days). Initial approval in Oct 18 required patients to have IV omadacycline for CAP on day one, followed by oral or IV therapy [19].
May 21Paratek submitted NDA to US FDA for CABP (Oral only loading dose regimen). [18]
Oct 19Application withdrawn by manufacturer. At the time of withdrawal, CHMP had considered recommending marketing authorisation for the treatment of infections of the skin and skin structures but not for community-acquired pneumonia (CABP); it considered that as other antibiotics were available for the infection, the single clinical study in patients with CABP did not provide sufficient evidence of effectiveness and another study was required to establish that omadacycline is an appropriate option. The company withdrew the application as it considered it not commercially feasible to market the drug for the restricted indication [16].
Jun 19PI in the US; nil elsewhere [2,3].
Oct 18Approved in US for treatment of adults with community-acquired bacterial pneumonia (CABP) [13].
Oct 18Filed in EU [12].
Oct 18US launch planned for Q1 2019 [14].
Aug 18FDA advisory committee recommends approval [11].
Feb 18Paratek completes submission of NDAs to US FDA for oral and IV omadacycline for Pneumonia and Skin Infections. Previous Qualified Infectious Disease Product and Fast Track designation for these indications will provide for a Priority Review of the NDAs, once accepted [10].
Apr 17Paratek plans to submit an NDA in the U.S. in Q1 2018 with an EMA submission later in 2018 [9].
Mar 15The company has completed clinical studies required to support initiation of PIII trials in ABSSSI and CABP indications; these studies are anticipated to start in 2015 [6].
Jan 13The FDA has granted Qualified Infectious Disease Product (QIDP) designation for both oral and intravenous formulations for treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The QIDP designation will confer access to incentives such as priority review, eligibility for fast-track status and 5-year extension of exclusivity on FDA approval [6].
Jul 11Novartis terminated its collaboration with Paratek on omadacycline, returning all rights to Paratek. Novartis´ reason for termination was that the timing for omadacycline´s regulatory approval had become uncertain [6].
Jun 11Filing for CABP planned for 2013 [1].

Category

Broad-spectrum antibiotic - a first in class aminomethylcycline
0.5%-1% of people develop CAP in the UK every year. 5-12% of adults who present to GPs with symptoms of lower RTI are diagnosed with CAP; 22-42% of these are admitted to hospital (about 100,000 hospital admissions each year in England). The mortality rate is 5-14% (patient.co.uk Feb/18).
Moderate to severe community-acquired pneumonia in adults
Oral

Trial or other data

Oct 20Paratek initiates a PIIIb trial to compare the safety and efficacy of IV and oral omadacycline to IV and oral moxifloxacin for treating adult subjects with CABP (EudraCT2020-002986-32; PTK0796-CABP-19302). The randomised, double-blind, multi-centre intends to enrol 670 patients in Bulgaria and may expand to Croatia, Georgia, Russia and Ukraine [19].
Feb 19Results of PIII OPTIC study (NCT02531438; n=774) are published. Omadacycline was noninferior to moxifloxacin (IV with transition to oral after 3 days each arm for total 7-14 days) for early clinical response (81.1 and 82.7%, respectively) with similar rate of adverse events (41.1 and 48.5%) [15].
Oct 18First-in-class specifically designed to overcome tetracycline resistance; offers an alternative to fluoroquinolones which have safety concerns, and comes as once-daily oral and IV formulations. No C. diff cases were observed in patients taking Nuzyra in clinical studies [14].
Apr 17Omadacycline meets its primary endpoint of noninferiority to moxifloxacin in a PIII trial 774 patients with community-acquired bacterial pneumonia. Paratek looked at how many patients in each cohort survived and improved on two of four symptoms in the 72 to 120 hours after treatment started and assessed the number of subjects whose symptoms cleared up in the five to 10 days after treatment ended. Omadacycline delivered on both counts. In the intention-to-treat population, 81.1% of patients in the omadacycline cohort responded to the experimental drug in the first three to five days of treatment. The number in the moxifloxacin arm was 82.7%, resulting in the trial hitting its primary endpoint of noninferiority. And omadacycline matched moxifloxacin against the second endpoint. The symptoms of more than 90% of subjects in both arms resolved in the post-treatment window [9].
Dec 16PIII (NCT02531438) is currently recruiting patients [8].
Jan 16NCT02531438 (EudraCT 2013-004071-13) is a PIII RCT of IV/oral omadacycline vs moxifloxacin in 750 patients with CAP. The study stared in Nov 15 and is due to complete Sep 17 [7].
Mar 12Paratek has reached agreement with the FDA on Special Protocol Assessments (SPA) for its PIII programme to support approval for treatment of serious (acute) bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The trial designs agreed upon through both SPAs are double-blind RCTs comparing omadacycline to standard of care therapies. The SPAs are the first to accommodate the FDA´s new directives on early response endpoints [4].

NuzyraAcute skin and skin structure infections in adults

Information

Nuzyra
New molecular entity
Paratek
Paratek

Development and Regulatory status

None
Filing withdrawn
Launched
Oct 19Application withdrawn by manufacturer. At the time of withdrawal, CHMP had considered recommending marketing authorisation for the treatment of infections of the skin and skin structures but not for community-acquired pneumonia (CABP); it considered that as other antibiotics were available for the infection, the single clinical study in patients with CABP did not provide sufficient evidence of effectiveness and another study was required to establish that omadacycline is an appropriate option [24].
Oct 18US launch planned for Q1 2019 [21]
Oct 18Approved in US for treatment of adults with acute skin and skin structure infections (ABSSSI) [20].
Oct 18Filed in EU [19].
Aug 18FDA advisory committee recommends approval [18].
Feb 18Paratek completes submission of NDAs to US FDA for oral and IV omadacycline for Pneumonia and Skin Infections. Previous Qualified Infectious Disease Product and Fast Track designation for these indications will provide for a Priority Review of the NDAs, once accepted [17].
Mar 15PIII trials are anticipated to start in 2015 [11].
Apr 14PII for ABSSSI [10].
Jan 13Paratek terminated its US-based PIII study of omadacycline in patients with complicated skin and skin structure infections (cSSSIs) in Nov 12, but has completed the clinical studies required to support initiation of PIII trials in the ABSSSI and CABP indications [8].
Jan 13The US FDA had granted Qualified Infectious Disease Product (QIDP) designation for both oral and intravenous formulations of omadacycline for treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The QIDP designation, which was provided under the Generating Antibiotic Incentives Now (GAIN) Act (enacted in July 2012), will confer access to incentives such as priority review, eligibility for fast-track status and five-year extension of exclusivity on FDA approval [7].
Jul 11Novartis terminated its collaboration with Paratek on omadacycline, returning all rights to Paratek. Novartis´ reason for termination was that the timing for omadacycline´s regulatory approval had become uncertain [6].
Jun 11Filing now planned 2013 [4].
Mar 10Filings planned for 2012 [2].
Oct 09PIII studies started in US Mar 09 and globally in Jul 09 [1].

Category

Broad-spectrum antibiotic a first-in-class aminomethylcycline
Acute bacterial skin and skin structure infections (ABSSSI), formally referred to as complicated skin and soft tissue infections, include infections with resistance to previously effective antimicrobials. Data published in 2009 showed that ABSSSI accounted for almost 870,000 hospital admissions in the US in 2004. This represents an increase of almost 30% in the incidence of this diagnosis over a 4-year period. This increase is attributed primarily to the spread of community-acquired MRSA (Ther Adv Infect Dis. 2017 Sep; 4(5): 143–161)
Acute skin and skin structure infections in adults
Oral

Trial or other data

Sep 19Results of PIII OASIS-2 (n=735) are published in the Lancet; it reports omadacycline (315 [88%] of 360) was non-inferior to linezolid (297 [83%] of 360) for early clinical response (percentage-point difference 5.0, 95% CI −0.2 to 10.3) in the modified intention-to-treat population [23].
Feb 19Results of OASIS-1 (NCT02378480; n=316) published. Omadacycline was noninferior to linezolid (IV with transition to oral after 3 days each arm for total of 7-14 days) with respect to early clinical response (84.8% vs. 85.5%, respectively), with a similar safety profile [22].
Jul 17In PIII OASIS-2 (NCT02877927) study (n=735) omadacycline was found to be non-inferior to linezolid for early clinical response. Clinical success at post therapy evaluation was 84.2% and 80.8% for omadacycline and linezolid respectively [16].
Apr 17Paratek present additional data from NCT02378480 at conference. Study shows omadacycline effective against common skin infections and pathogens including MRSA. In the modified intention-to-treat population (n=455) at post-treatment evaluation, clinical success rate for omadacycline was 86.1% vs 83.6% for linezolid [15].
Dec 16Collection of primary outcome data should complete May 2017 [14].
Aug 16Second PIII study (NCT02877927) of oral-only omadacycline in ABSSSI starts. Approximately 700 patients will be enrolled. Primary outcomes are number of subjects with clinical success at the early clinical response (ECR) assessment 48-72 hours after the first dose of study drug and clinical response at the post therapy evaluation, also known as ‘test of cure’ [13].
Jun 16Paratek announce that omadacycline met all primary and secondary efficacy outcomes in PIII OASIS study (NCT02378480); omadacycline was generally safe and well-tolerated [13].
Jun 15PIII trial started (NCT02378480, EudraCT 2013-003644-23) comparing omadacyline with linezolid in 650 patients with ABSSSI. Trial is due to complete October 2016 [12].
Apr 14No clinical trials registered for omadacycline in the US clincial trials registry [9].
Mar 12Paratek has reached agreement with the FDA on Special Protocol Assessments (SPA) for its PIII programme to support approval for treatment of serious (acute) bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). The trial designs agreed upon through both SPAs are double-blind RCTs comparing omadacycline to standard of care therapies. The SPAs are the first to accommodate the FDA´s new directives on early response endpoints [5].
Oct 09There are two registered PIII studies of similar design, one US (NCT00865280; PTK 0796-CSSI-0804) and the other global, (NCT00876850; PTK 0796-CSSI-0805), both comparing oral and IV PTK 0796 vs linezolid to treat cSSSIs. The primary outcome is clinical success at 4 weeks follow up. Each study is enrolling around 790 patients and are expected to be completed by mid-2010. PIII studies in additional indications such as CABP are planned [1].
Oct 09Paratek entered into a collaborative development with Novartis. The two companies will share responsibility and costs for worldwide development and Novartis will have the exclusive right to commercialise PTK 0796 [1].
Oct 09A PII study met its primary safety and tolerability endpoint, demonstrating no relevant differences between PTK 0796 and linezolid in incidence or pattern of adverse events. In the evaluable population of patients (n=188), the clinical success rates were 98.0% and 93.2% for PTK 0796 and linezolid respectively [1].
Oct 09PTK 0796 has a spectrum broad enough for single-agent treatment of life threatening infections such as complicated skin and skin structure infections (cSSSI) and moderate to severe community acquired bacterial pneumonia with activity against resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), multi-drug resistant Streptococcus pneumoniae (MDRSP) and vancomycin-resistant enterococci (VRE). It is given by a 30 minute IV infusion or orally, both once daily [1].