Adding further evidence about the global threat of the increase of antimicrobial-resistant (AMR) infections and dearth of new antibiotics to treat those conditions, Thomas Cueni, chair of the AMR Industry Alliance, said the findings from the alliance’s newly released report are “a wake-up call” as they estimate current investments in AMR-relevant R&D are not enough to sustain a viable pipeline that will be needed to combat infectious diseases globally. If AMR remains unchecked, the annual death toll could climb from 700,000 each year to 10 million by 2050, and the economic impacts could be on par with those of the 2008 financial crisis, the report notes.
The alliance, formed in 2017, includes a membership of more than 100 biotechnology, diagnostics, generics and research-based biopharmaceutical companies and trade associations, and the 2020 report is the organization’s second and is based on a comprehensive member survey, with 65 out of 91 eligible members responding.
In terms of research and development, the alliance found that the life sciences industry remains the dominant funder of AMR-relevant R&D, with $1.6 billion invested during 2018. That is in sharp contrast to the approximately $500 million that the public sector invests annually in AMR-relevant R&D.
Particularly troublesome is the amount of investments being directed toward late-stage clinical research. They are “at concerning levels,” according to the report. “This contrasts with a promising biotech preclinical pipeline and new rapid infection detection tests being developed by diagnostics companies.”
The alliance reported that 74% of companies surveyed indicated that they are likely to increase investments in AMR if commercial models improve. “Alliance members are eager to find partners in piloting new reimbursement mechanisms and incentives that improve patient access and enable sustainable private investment in the development of new tools to tackle AMR.”
Commenting on the findings in the report, Kevin Outterson, founding executive director of CARB-X, said, “Most assessments of the current clinical pipeline of antibiotics find it to be fragile and inadequate for the unmet medical need. Improving the future clinical pipeline will require more generous funding for R&D to advance these preclinical products, including more substantial private investment, which has decreased in the past few years. Private capital appears to be waiting on the sidelines for changes in antibiotics reimbursement, as the current systems disincentivizes innovation.”
The report includes several case studies that present work being conducted by its members on improving access to and optimizing use of antimicrobials, vaccines and diagnostics tools as well as promoting the responsible manufacture of antibiotics. The survey found that all responding companies reported that they are taking a wide range of measures to promote appropriate use of antibiotics in order to slow the emergence of resistance, prolong the effectiveness of antimicrobials and improve patient outcomes.
The alliance said it is planning to host a high-level meeting to discuss the findings with the AMR global health community in March.
Year to forget
Although there has been a dramatic surge of interest among individual companies that have therapeutics in their pipelines to combat the spread of the novel coronavirus infection that has emerged in Wuhan, China, the reality is that companies in the infectious diseases space are struggling, with investor sentiment still at an all-time low. As a group, public companies have endured a very tough year with many seeing their share price valuations drop dramatically. As a result, the BioWorld Infectious Disease index closed the year down 34%. (See BioWorld Infectious Disease index, below.)
The deep divide between antibiotics R&D and market pull has claimed several antibiotics innovators. Achaogen Inc. was forced to file for Chapter 11 bankruptcy nine months after the U.S. launch of its new antibiotic, Zemdri (plazomicin), to treat complex urinary tract infections and carbapenem-resistant Enterobacteriaceae.
Another antibiotics developer casualty is Motif Bio plc, of New York, which has wound down its operations. In February, the company’s stock value collapsed on news that the FDA had issued a complete response letter requesting more liver toxicity data in its NDA for iclaprim, an antibiotic in development to treat acute bacterial skin and skin structure infections caused by gram-positive pathogens.
To cap off the year, Morristown, N.J.-based Melinta Therapeutics Inc. said it had initiated voluntary proceedings under Chapter 11 of the U.S. Bankruptcy Code in the U.S. Bankruptcy Court for the District of Delaware. In addition, it entered a restructuring support agreement with the lenders under its senior credit facility, Deerfield Private Design Fund III LP and Deerfield Private Design Fund IV LP. They are acquiring the company as a going concern by exchanging $140 million of secured claims arising under its senior credit facility for 100% of the equity to be issued by the reorganized company relating to a prenegotiated Chapter 11 plan of reorganization.
With Achaogen, Melinta and Motif dropping off the BioWorld Infectious Disease index, two new members have been added in their place: the 2019 IPO graduate Vir Biotechnology Inc., of San Francisco, and Gaithersburg, Md.-based Novavax Inc.
Vir, the infectious disease specialist, made an inauspicious debut after pricing a $142.9 million IPO in October. The company shares (NASDAQ:VIR) fell 30% to $14.02 on the first day of trading. It is led by former Biogen Inc. CEO George Scangos and is largely owned by Arch Venture Partners and Softbank's Vision Fund. The share price did not recover and by the end of the year shares were trading at $12.57.
The company is working on developing therapies targeting hepatitis B virus, influenza A, HIV and tuberculosis. VIR-2218, a hepatitis B virus (HBV)-targeting small interfering ribonucleic acid being developed for the functional cure of HBV, has completed phase I/II dosing of all patient cohorts receiving 50 mg to 200 mg. VIR-2482, a monoclonal antibody being developed as universal prophylaxis for influenza A, is also in an ongoing phase I/II trial.
In January, Vir’s shares soared 62%, with investors jumping on board because it is working to rapidly determine whether its previously identified anti-coronavirus monoclonal antibodies bind and neutralize the newly emerged Wuhan coronavirus.
Novavax has also benefited from an extensive history of working with coronaviruses and developing vaccine candidates, with its shares (NASDAQ:NVAX) up by more than 113% so far this month. The company has initiated development of a vaccine candidate against 2019-nCoV.
Also catalyzing the index’s almost 7% jump in valuation month-to-date is Yonkers, N.Y.-based Contrafect Corp., whose shares (NASDAQ:CFRX) have risen 61%. The company is focused on the discovery and development of direct lytic agents, including lysins and amurin peptides, for the treatment of antibiotic-resistant infections. This month, the first patient was dosed in the company’s phase III DISRUPT (Direct Lysis of Staph aureus Resistant Pathogen Trial) study of exebacase in patients with S. aureus bacteremia, including right-sided endocarditis. The company said it plans to conduct an interim futility analysis following the enrollment of approximately 60% of the study population.