Type: Engineered (Humaneered®) anti-human granulocyte macrophage-colony stimulating factor (GM-CSF) monoclonal antibody designed to prevent and treat cytokine storm.
Status: H.C. Wainwright on October 14 initiated coverage of Humanigen with a “buy” rating, a day after the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) said it launched the fifth trial conducted through the public-private partnership Accelerating COVID-19 Therapeutic Innovations and Vaccines program (ACTIV-5), also known as the Big Effect Trial (BET).
ACTIV-5/BET (NCT04583969) is designed to compare Gilead Sciences’ Veklury® (remdesivir) in combination with two late-stage antibody treatment candidates—Humanigen’s lenzilumab and Skyrizi® (risankizumab-rzaa), the Boehringer Ingelheim/AbbVie monoclonal antibody now marketed for moderate to severe plaque psoriasis—to assess if they show enough promise against COVID-19 to be advanced into larger clinical trials. ACTIV-5/BET will enroll adult volunteers hospitalized with COVID-19 at as many as 40 U.S sites, twice as many as originally planned. Approximately 100 hospitalized volunteers will be assigned to each study arm—200 participants total—with each study site testing no more than three investigational treatments at once.
Volunteers assigned to receive risankizumab will be administered a single intravenous dose on day 1 of the study. Study participants assigned to receive lenzilumab will be given a 600 mg intravenous infusion every eight hours, for a total of three doses. The study is set to start on October 30, with an estimated primary completion date of January 8, 2021, and an estimated completion date for the full study of July 1, 2021.
Humanigen said September 23 it launched a collaboration with Thermo Fisher Scientific to expand the manufacturing capacity for lenzilumab, in order to support a potential Emergency Use Authorization (EUA). Thermo Fisher began technical transfer of the lenzilumab bulk drug substance process, with commercial scale production potentially starting before the end of 2020.
The multi-year manufacturing partnership, whose value was not disclosed, added to large scale commercial production efforts that include partnerships with Lonza and Catalent, in advance of the potential EUA this year and subsequent commercialization of lenzilumab.
On September 4, Humanigen’s board decided to carry out a 1-for-5 reverse split of its outstanding common stock shares, citing the need to meet corporate objectives that include satisfying the minimum bid price requirement in connection with the company’s application to list its common stock on the Nasdaq Capital Market and making additional shares available for issue in the future. The split will take effect with the start of trading on September 14, and reduce the company’s outstanding shares of common stock from approximately 211 million shares to approximately 42 million shares.
Holders of a majority of the company’s outstanding shares agreed in July to a reverse stock split, and gave the company authority to determine the split ratio before July 29, 2021. Humanigen stock is quoted on the OTC Markets (OTCQB) Venture Market with only limited trading.
Humanigen Chairman and CEO Cameron Durrant, MD, MBA, told GEN August 25 that the company will “shortly” recruit its first patient in Brazil, where regulatory agency Anvisa earlier that month approved the company’s launch of a Phase III study of lenzilumab in COVID-19 patients in Brazil.
The multicenter, randomized, placebo-controlled, double-blinded clinical trial—similar to a Phase III trial (NCT04351152) being conducted in the U.S.—focuses on hospitalized severe and critical adult COVID-19 patients at high risk of disease progression. Humanigen is working with the contract research organization Clinical Trial & Consulting (CTI) to conduct the potential registrational trial, which is about halfway through enrollment, and expected to finish by end of September or early October, with data expected to be released about a month later.
Should the trials prove positive, Humanigen envisions applying for a BLA, and based on the strength of tits data obtaining emergency use authorization (EUA) for lenzilumab, followed by a launch of initial commercial activities as soon as the fourth quarter. Within six months, the company envisions an expanded product launch and commercialization, followed by work on additional dose formulations and further international studies.
“At some point, provided those [Phase III and BET] studies read out positively—and we’re confident that they will—we could see ourselves going into earlier stages of the disease as well. But right now, the highest unmet medical need is in the severe and critical stages, we believe,” Durrant told GEN. “We think that lenz is, or has the potential to be, a leading treatment near term for patients that could have serious and potentially fatal outcomes, who are high risk and hospitalized.”
In July, Humanigen signed a clinical trial agreement with the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), Division of Microbiology and Infectious Diseases (DMID) to evaluate lenzilumab in the NIAID-sponsored Big Effect Trial (BET) in hospitalized patients with COVID-19.
The NIH confirmed to GEN it has awarded contracts totaling $25.8 million to Leidos Biomedical Research toward managing, overseeing, and conducting the trial, the most recent being $14.3 million awarded on August 4.
BET is intended to build on initial data from NIAID’s Adaptive COVID-19 Treatment Trial (ACTT), which showed that Gilead’s remdesivir may improve time to recovery in hospitalized patients with COVID-19. BET is designed to assess the combination of lenzilumab and remdesivir on treatment outcomes versus placebo and remdesivir in hospitalized COVID-19 patients. The trial is expected to enroll 100 patients in each arm of the study with an interim analysis for efficacy after 50 patients have been enrolled in each arm, Humanigen said.
“With data from the BET and our ongoing Phase III study, we will have data from approximately 500 hospitalized COVID-19 patients,” Durrant stated.
In June, Mayo Clinic researchers published a preprint study at medRxiv.org showing positive data associated with a Phase III potential registration study (NCT04351152) that the company said was the first clinical use of lenzilumab in 12 COVID-19 patients hospitalized in Mayo’s system with severe or critical pneumonia due to the virus. Lenzilumab led to rapid clinical improvement with a median time to recovery of five days, median time to discharge of five days, and 100% survival to the data cutoff date. Patients also showed rapid improvement in oxygenation, temperature, inflammatory cytokines, and key hematological parameters consistent with improved clinical outcomes, Humanigen added.
At the data cut-off point, according to Humanigen CEO Cameron Durrant, MD, MBA, 11 of the 12 patients were discharged from the hospital. All 12 had at least one risk factor associated with poor outcomes, such as age, smoking history, cardiovascular disease, diabetes, chronic kidney disease, chronic lung disease, high BMI, and elevated inflammatory markers, with several patients having multiple such risk factors. The patients, who were hospitalized in the Mayo Clinic system, all required oxygen supplementation and had elevation in at least one inflammatory biomarker prior to receiving lenzilumab.
All patients had at least one co-morbidity associated with poor outcomes in COVID-19, with several patients having multiple co-morbidities: 58% had diabetes mellitus, 58% had hypertension, 58% had underlying lung diseases, 50% were obese (defined as a BMI greater than 30), 17% had chronic kidney disease and 17% had coronary artery disease. The median age was 65 years.
On June 16, Humanigen released additional analysis of the data comparing patients with similar baseline characteristics treated with lenzilumab to patients treated with Gilead Sciences’ remdesivir. Patients treated with lenzilumab for a single day showed rapid clinical improvement with a median time to improvement of five days and a median time to recovery of five days—compared with a median time of 10 days for both measures in patients treated with remdesivir over 5 days, and a median of 11 days for both measures in patients treated 11 days with remdesivir.
Neither data set included a placebo arm, and the lenzilumab cohort was small, Humanigen acknowledged.
COVID-19: 200 Candidates and Counting
To navigate through the >200 potential therapeutic and vaccine options for COVID-19, GEN has grouped the candidates into four broad categories based on their developmental and (where applicable) clinical progress:
● FRONT RUNNER – the most promising therapeutics/vaccines based on clinical progress, favorable data or both.
● DEFINITELY MAYBE – earlier phases with promising partners, or more advanced candidates in development that have generated uneven data.
● KEEPING AN EYE ON… – interesting technology, attracting notable partners, or both, but preliminary data.
● TOO SOON TO TELL – longshots pending additional experimental and/or clinical data.
GEN has also tagged the most common treatment types: