Innovation Pharmaceuticals Inc (IPIX)

[slcimmuno]

Brilacidin ABSSSI Approval Odds

to Sok's point (it's been a quieter board of late), and with whom i agree (we all must remember The Science is Strong with This One), thought id post some data/commentary i've come across that bodes well for Brilacidin. i've divided into two categories:

1) Success rates by stage of clinical trial
2) FDA anti-infectives advisory committee's unanimous votes on ABSSSI drugs

recent funding/legislative pushes (allocating more $ to NIH; putting more pressure on FDA to expedite drug development, esp antibiotics) also should be factored in, increasing chances for approval. but of course it's the clinical results to date that speak loudest... the solid science behind Brilacidin----efficacy comparable/slightly better to Daptomycin, current best in class; a better safety profile than single-dose Orativancin... see Biodoc's post below to this point. and as NR commented, there's ~ 98% chance similar results from the Ph II will carry over into Ph III for the single-dose at .8mg, and a decent (over 60%) of a significantly better result.

link to biodoc's 12.14.14 post on Orbactiv (orativancin)
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=109052476

link noretreat's 1.5.15 post on what P2b means
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=109631189

1) CLINICAL TRIAL DATA (SUCCESS RATES)

a) Article: Can Clinical Trial Changes Increase Drug Approvals (Jan 2014)
http://www.clinicalinformaticsnews.com/cln/2014/1/13/can-clinical-trial-changes-increase-drug-approvals.html

EXCERPT
They [citing this January 2014 study in Nature Biotechnology: "Clinical Development Success Rates for Investigational Drugs"... full access behind a pay wall] found the likelihood of approval (LOA) from Phase 1 to be about 10% for all indications, and 15% for lead indications. From Phase 1 to Phase 2 success rates are about 65%; from Phase 3 to new drug applications success rates fall again between 60% and 68%. The biggest drop off comes moving from Phase 2 to Phase 3, with only 32% of all indications advancing.

The numbers are somewhat less encouraging than previous studies. DiMasi et al. and Kola et al. found higher LOA rates from Phase 1 (19% over 50 years and 11% over 10 years respectively), but both studies looked at far fewer companies, and the current study purposefully considered the success of all indications, rather than just a lead indication.

[...]

They [study authors] believe that changing trial design—especially communication with regulators at the end of Phase 2— could help improve rates. The authors point out that heterogeneous trials are far more likely to fail than trials built on specific biomarkers. “The adoption of adaptive trial design may facilitate the identification of targeted subsets of patient populations before study completion,” [e.g., M-ITT] they suggest. “Greater flexibility with alternative surrogate endpoints,… and improved methodologies for assessing patient benefit-to-risk are some areas where improvements can be made.” [SEEMS LIKE CTIX IS DOING IT RIGHT]

b) Article: A Way To Increase Drug R&D Success Rates (Feb 2014)
http://www.forbes.com/sites/johnlamattina/2014/02/07/a-way-to-increase-drug-rd-success-rates/

EXCERPT
They [the Jan 2014 Nature Biotechnology article authors] have analyzed 2003 – 2011 data from 835 companies including large pharma/biotech, small to mid-sized pharma/biotech, and emerging biotech. Their data set includes 4,451 drugs with 7,372 independent clinical development paths (the larger number of the latter is due to companies exploring a single compound for multiple indications such as for different types of cancer). They have analyzed the data in many ways, including survival rates by therapeutic area, by molecule type (small versus biologicals) and by lead or non-lead indication. For a drug R&D aficionado, the data are fascinating.

What was especially interesting to me was the breakdown of survival rates by clinical stage. The stage of greatest compound attrition was in phase 2 – the place where compounds are first tested in people with the disease you’re trying to treat. The data show that only 32% of compounds entering phase 2 make it into phase 3. This is not surprising. While a compound might have been tested in animal models of disease, phase 2 is the first real test of the original concept of the research program. For me, phase 2 was the most important step in the development of a potential new drug, and positive results from these clinical proof-of-concept (POC) studies were always the most memorable.

[...]

Survival gets better once a compound makes it to phase 3, where 60% advance to regulatory filing.

[...]

However, the main surprise to me in reading this paper was the high rate of attrition in phase 1. Only 64% of compounds are making it through this stage.

[...]

Why then don’t more compounds clear phase 1? At times, the in vitro and in vivo preclinical models don’t predict what will happen in humans. But this shouldn’t happen 36% of this time. This should be a relatively rare occurrence if the candidate selection criteria are vigorous and enforced. I can only speculate as to why these number are not higher. As this survey includes a wide variety of R&D organizations, it could be that there are major differences in the rigor of the preclinical studies conducted by different organizations. [AND THIS IS WHERE CTIX BENEFITS FROM ALL THE EARLIER HIGHQUALLITY PYMX WORK ON ITS DEFENSIN MIMETICS PLATFORM, THE NIH AND DEF DEPT GRANTS ETC]. For example, small companies and start-ups might not have the resources, expertise or time to conduct a lot of upfront studies. I do recall that in my time in big pharma, some early development compounds that we reviewed as potential licensing candidates were missing studies that we would have routinely done at that point.

2) 2014 FDA ABSSSI VOTES (UNANIMOUS)

Another good sign for Brilacidin once up for approval (again, odds look good) is that, in 2014, the FDA's Anti-Infective Drug Advisory Cmte vote -- which is not binding but typically tips the approval in one direction or the other (thumb up/thumb down) -- was unanimous in their approval for Dalbavancin/Tedizolid… same, the advisors were unanimous, in their support of Astella’s anti-fungal (Cresemba for aspergillosis). [RECALL FOX CHASE RESEARCHERS ARE WORKING WITH CTIX COMPOUNDS SHOWING ANTI-FUNGAL AND GRAM-NEGATIVE PROPERTIES; SEE LINKS BELOW] The cmte voted 8-2 with one abstention on whether to recommend it for mucormycosis, a second indication. (Note both indications had earlier been granted QIDP status.)

Article on PYMX (without mentioning the company) anti-fungal research
Defensin Mimetics Show Antifungal Activity (January 2012)
http://www.aspergillusblog.blogspot.com/2012/01/defensin-mimetics-show-antifungal.html

http://cellceutix.com/cellceutix-anti-fungal-compounds-awarded-1-5-million-sbir-grant/#sthash.97ngcrQN.dpbs

Article: Which of FDA's Drug Advisory Committees Were Most Active in 2014
http://www.raps.org/Regulatory-Focus/News/2015/01/22/21142/Which-of-FDAs-Drug-Advisory-Committees-Were-Most-Active-in-2014/

Anti-Infective Drugs Advisory Committee (AIDAC)
Total Meetings in 2014: 3
Breakdown of Votes:
3 Yes votes:
• 12-0 for Durata Therapeutics’ dalbavancin for acute bacterial skin and skin structure infections (half-day meeting)
• 14-0 for Trius Therapeutics’ tedizolid for acute bacterial skin and skin structure infections (half-day meeting)
• Cerexa’s Ceftazidime-Avibactam
o 11-1 for the combination to treat complicated intra-abdominal infections (cIAI), when limited or no alternative treatments are available
o 9-3 for the combination to treat complicated urinary tract infections (cUTI), including acute pyelonephritis, when limited or no alternative treatments are available
1 No vote:
• Cerexa Inc.’s Ceftazidime-Avibactam
o 12-0 against the combination to treat aerobic gram-negative Infection, when limited or no alternative treatments are available
o 11-1 against the combination to treat aerobic gram-negative infections when no alternative treatments are available
1 non-voting meeting:
• The AIDAC discussed issues related to clinical development programs and clinical trial designs for antibacterial products for the treatment of patients with serious bacterial infections for which there are limited or no therapeutic options. They reviewed ways in which to streamline development.

IMAGES related to Clinical Trial Success Rates (note infectious disease drugs fare better than other drugs)

Phase Success and Likelihood of Approval (LOA) Rates / Lead vs All Indications


Phase Success and LOA from Phase 1 by Disease for All Indications


Clinical Development Success Rates for Investigational Drugs


Root-Cause Analysis for 359 Phase 3 and 95 NDA/BLA Suspended Programs