New Medicines

Acute bacterial skin and skin structure infections and hospital acquired bacterial pneumonia


New molecular entity
Motif Bio
Motif Bio

Development and Regulatory status

Jun 21Motif Bio investors vote to reject a reverse takeover that might have rescued the company, but some consider would have given too much to the existing directors. No news on whether iclaprim was sold. As the company has now collapsed, assume all development (at least for now) is discontinued [29].
May 20Iclaprim listed as a ´legacy programme´ on company website. The website indicates that Motif BioSciences Inc has ceased all operations and has engaged Tamarack Associates to facilitate the sale of iclaprim. [28]
Jul 19Company seeking partners for commercialisation in EU. [26]
Feb 19Motif Bio received a complete response letter (CRL) from the US FDA regarding its NDA for iclaprim for treatment of ABSSSI. The CRL stated that the FDA cannot approve the NDA in its present form and has requested the company to provide additional data to further evaluate the risk for liver toxicity before the NDA approval. [25]
Jan 19Company are seeking partners to support commercialisation in the EU. [24]
Aug 18Granted priority review in US [23]
Jun 18Filed NDA in US for ABSSSI. [22]
Feb 18Company pipeline states; PIII trials in ABSSSI completed; NDA submission planned for Q1 2018.[21]
Jul 15The FDA has designated Motif Bio’s novel antibiotic iclaprim as a Qualified Infectious Diseases Product (QIDP). QIDP designation is used to help incentivise production of new antibiotics, and makes icalrpim eligible for priority review and fast track designation, as well as 10 years of market exclusivity. Motif, which specialises in novel antibiotics, says it believes iclaprim is the first drug in the dihydrofolate reductase inhibitor class to receive QIDP designation. The new designation covers the indications of acute bacterial skin and skin structure infections (ABSSSI) and hospital acquired bacterial pneumonia (HABP), two of the most common and serious forms of bacterial infection. This includes illnesses caused by prevalent resistant strains such as MRSA (methicillin-resistant Staphylococcus aureus) and MDRSP (multi-drug resistant Streptococcus pneumoniae) [13].
Dec 10Development appears to be continuing (see below) [12].
Oct 09Arpida has withdrawn the marketing application iclaprim and terminated further development plans after the CHMP reached a negative opinion for its use in the treatment of complicated skin and soft tissue infections [11]
Feb 09Filed in Canada
Jan 09FDA Complete Response letter states that they cannot approve the application for iclaprim in its current form and that further data is necessary to show efficacy to gain approval. The FDA letter stated that the NDA did not show the efficacy of iclaprim for cSSSI within an acceptable non-inferiority margin. The FDA requires further data to evaluate the benefits and risks of iclaprim for cSSSI. Jan 09 (9)
Nov 08FDA panel voted 17-2 against recommending approval for the treatment of complicated skin and skin structure infections. It failed to demonstrate equivalent cure rates vs linezolid and there were safety concerns (8).
Aug 08Filed in EU for complicated skin and soft tissue infections Aug 08 (5).
May 08US FDA accepted NDA for complicated skin and skin structure infections (may 08 ) (4)
Dec 07Filed in US for skin and soft tissue infections Dec 07 (3)
Dec 07PII trials in nosocomial pneumonia in US (Dec 07) (3)
Jan 07Company hope to file in US 2007; it has fast track status (1). Positive results from ASSIST-2 (2).
Oct 03PI clinical trials in nosocomial infections in EU (Oct 03) (3)


Dihydrofolate reductase inhibitor; broad-spectrum antibiotic designed to be effective against multi-drug resistant bacteria.
In England there were ~190,000 finished consultant episodes of skin infections including cellulitis, local infections of skin tissues and cutaneous abscess in 2017-18. Of these, it is estimated that ~20% fail empirical therapies. A small proportion (up to 10%) would be likely to receive targeted antimicrobial therapy based on reported antibiotic resistance rates in the 2018 ESPAUR report. [27]
Acute bacterial skin and skin structure infections and hospital acquired bacterial pneumonia

Trial or other data

Oct 17In PIII Revive-2 study, iclaprim achieved primary endpoint of non-inferiority against vancomycin (current standard of care), with clinical cure in 78% (vancomycin result not stated). Resolution/ near resolution at end of therapy was achieved in 54.6% and 55.4%, respectively [20].
Apr 17In PIII REVIVE-1 trial, iclaprim was used in acute bacterial skin and skin structure infections and achieved non-inferiority (10% margin) compared to vancomycin at both early time point (48 to 72 hours after the start of treatment) 80.9% and 81% and at the test of cure endpoint, 7 to 14 days after study drug discontinuation, 84.2% vs 87% respectively [19].
Jan 17PIII REVIVE-1 study (NCT02600611) has completed recruitment. Collection of primary outcome data was expected to complete Dec 16. PIII REVIVE-2 study (NCT02607618) is still recruiting and expected to complete collecting primary outcome data in Aug 17 [18].
Mar 16Motif Bio announce first patient dosed in the REVIVE trial programme; they expect that both studies will be complete by 2H17. Both REVIVE-I & REVIVE-II are multi-centre, multi-national trials of similar design: if successful, they are expected to satisfy requirements for approval by both the EMA and the FDA [17].
Nov 15Second PIII study (REVIVE-II, NCT02607618) begins [16]
Nov 15PIII study (REVIVE-1; NCT02600611) to assess the efficacy and safety of iclaprim compared to vancomycin for treatment of skin and skin structure infections begins. 600 adults will be recruited in the US. Primary outcome is ≥20% reduction in lesion size at 48 to 72 hours; data collection should complete Aug 17 [15].
Sep 15FDA granted Fast Track designation for iclaprim IV [14].
Dec 10Subsequent to the complete response letter issued in the US in Jan 2009, the FDA has issued updated draft guidance (August 2010) recommending new clinical endpoints and study populations in a newly defined indication, Acute Bacterial Skin and Skin Structure Infections ABSSSI. The FDA has agreed that pooled data from the two existing PIII studies together with further analysis and conditions was basically acceptable for a resubmission under the new guidance. This indicates that one additional study may be sufficient to gain approval. The company is planning further trials in the US and the EU [12].
Oct 08Data from a combined analysis of ASSIST-1 and ASSIST-2 were presented at the 48th Interscience Conference on Antimicrobial Agents and Chemotherapy)/Infectious Diseases Society of America 46th annual meeting. 991 adults with cSSSIs were treated for 10 to 14 days with either 0.8 mg/kg iclaprim or 600 mg linezolid twice daily. The clinical cure rate at the test of cure visit was 82.2% and 85.3% respectively in the ITT population. The pre-specified non-inferiority margin was -12.5%, and this was met in in both trials. The MRSA eradication rate was 76.4% and 78.7%, respectively (7).
Oct 08Results from ASSIST trials (n=991): iclaprim showed high clinical cure rate similar to those of linezolid in complicated skin and skin structure infections caused by G+ve bacteria, including MRSA. In a combined efficacy analysis, the clinical cure rate at the test-of-cure visit was 82.2 % for iclaprim vs. 85.3 % for linezolid in the intent-to-treat population and cure rates were 92.3 % and 97.8 %, respectively, in the per protocol population. Data from the studies also show that iclaprim showed a high eradication rate for MRSA (76.4 %), which was comparable to that of linezolid (78.7 %). Adverse events were found to be less frequent among patients treated with iclaprim vs. linezolid. (5)
Jan 07ASSIST-1 trial directly compared iclaprim with linezolid and demonstrated equivalent efficacy. ASSIST-2 results due 2007 (1). ASSIST-2 (iclaprim vs. linezolid) has met primary endpoint of statistical non-inferiority in the clinical cure rate; the safety profile that was demonstrated in ASSIST-1 was confirmed (2).