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Humanigen (HGEN) has had about as many successful escapes over the years as Harry Houdini. But this week, it was many investors who broke free of owning its shares, after the company’s COVID-19 antibody lenzilumab failed an NIH-sponsored clinical trial.
After the close of trading Tuesday, Humanigen announced preliminary topline data acknowledging that lenzilumab missed its primary endpoint in the Accelerating COVID-19 Therapeutic Interventions and Vaccines 5 (ACTIV-5)/Big Effect Trial (BET-B; NCT04583969) conducted by the NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The study compared whether lenzilumab plus Gilead Sciences’ antiviral drug Veklury® (remdesivir) was more effective than placebo plus remdesivir in hospitalized COVID-19 patients.
Lenzilumab plus remdesivir did not achieve statistical significance on the primary endpoint, namely the proportion of patients with baseline CRP<150 mg/L and age<85 years, alive and without mechanical ventilation through Day 29, according to Humanigen. The company also reported “a non-significant trend” toward a reduction in mortality in the overall patient population, but no new safety signals attributed to lenzilumab.
“While the ACTIV-5/BET-B study showed signs of a clinical effect, the benefit demonstrated was not able to confirm the positive results we saw in our Phase III LIVE-AIR study,” Humanigen Chairman and CEO Cameron Durrant, MD, said in a statement.
LIVE-AIR (NCT04351152) assessed lenzilumab in hospitalized COVID-19 patients, with a primary endpoint of survival without ventilation (SWOV). LIVE-AIR showed lenzilumab improved the likelihood of SWOV with a 54% relative improvement in the likelihood of SWOV vs. placebo, according to a preprint posted May 5 on medRxiv by researchers from Humanigen and clinical partners that included the Mayo Clinic and Emory University.
Based on LIVE-AIR, which recruited 520 patients, the NIH modified its primary endpoint for the study to SWOV—a change Humanigen said at the may enable it to use ACTIV-5/BET-B as a confirmatory study to support a future Biologics License Application (BLA). The NIH also expanded ACIV-5/BET-B to 550 patients, though only 473 took part, NIAID reported on ClinicalTrials.gov.
In announcing the topline readout from ACTIV-5/BET-B on Tuesday, Durrant suggested that the size of the patient population may have accounted for the disappointing results: “In order to prove the therapeutic benefits of immunomodulators, platform studies comprising thousands of patients have been necessary.”
“With the continued resurgence of COVID-19, further exploration of variant agnostic treatments to improve outcomes in hospitalized COVID-19 patients should be a priority,” Durrant added.
Investors responded to the clinical setback by punishing Humanigen with a stock sell-off that sent the company’s shares cratering 80% on Wednesday, to just 60 cents a share from $2.99 at Tuesday’s close.
“Following the release of these data, we expect the company to de-emphasize its COVID-19 program, and strategically realign its focus on company sponsored, as well as partner sponsored programs,” Joseph Pantginis, a Managing Director of Equity Research at H.C. Wainwright who focuses on the healthcare sector, wrote Wednesday in a research note quoted by analyst rating website TipRanks.
Humanigen has not said what its next move will be for lenzilumab.
Lenzilumab is a “humaneered” monoclonal antibody designed to prevent or minimize the cytokine release syndrome that precedes lung dysfunction and acute respiratory distress syndrome (ARDS) in serious cases of SARS-CoV-2 infection. It does so by targeting and neutralizing granulocyte macrophage-colony stimulating factor (GM-CSF), a key cytokine in the initiation of cytokine storm.
“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,” Durrant told GEN in 2020.
A year later, Humanigen sought Emergency Use Approval of lenzilumab as a treatment for patients hospitalized with COVID-19—only to be rejected in September 2021, a setback that sent company shares tumbling more than 50%.
Humanigen finished the first quarter with a net loss of $21.278 million, improved from a $65.567 million net loss in Q1 2021, on revenue of $1.036 million, up from $486,000 a year earlier. As of March 31, the company reported $68.948 million in cash and cash equivalents, down 1.5% from three months earlier.
However, Humanigen finished 2021 with a $236.649 million net loss, more than double its $89.535 million net loss a year earlier—largely due to a near-tripling of R&D costs due to a $143.9 million increase in manufacturing expenses, including consulting fees, and a $1.7 million increase in internal costs that were mainly compensation-related. The increased expenses were partially offset by a $5.2 million drop in clinical trial expenses for lenzilumab.
Humanigen’s gravest challenge came in 2015, when under its former name of KaloBios Pharmaceuticals, it averted liquidation through an investor share purchase agreement that sent the share price rocketing from $2.07 a share to more than $40, once it became known that the investors included “Pharma Bro” Martin Shkreli—who was released from a federal prison in May after serving most of a seven-year sentence following conviction on security fraud and conspiracy charges.
Shkreli took over as CEO as part of rescuing KaloBios, which was incorporated in 2000 and re-incorporated under that name the following year. A month later, Shkreli was arrested on securities fraud charges related to another company he founded years earlier, Retrophin. While none of the charges related to KaloBios, the arrest and global publicity surrounding Shkreli plunged KaloBios into Chapter 11 bankruptcy—from which it emerged in 2016 led by Durrant.
The company renamed itself Humanigen a year later, then restructured its debt through transactions completed in 2018. Today the company focuses on infectious diseases as well as cancer. In addition to the COVID-19 related indication, lenzilumab is also in clinical development for non-Hodgkin lymphomas (prophylaxis with Yescarta® and Tecartus®, both marketed by Kite, a Gilead Company), prevention/treatment of acute graft vs. host disease; and chronic myelomonocytic leukemia.
Applied Genetic Technologies (AGTC)
Shares of Applied Genetic Technologies plummeted 54% on Wednesday. Shares fell from $0.8475 to $0.3899 the day after AGTC announced the pricing of its $10 million public offering. The company offered 16,666,667 shares and accompanying warrants to purchase up to the same number of shares at 60 cents a share plus warrant, minus underwriting discounts and commissions.
The company said it would use proceeds to fund its ongoing Skyline and Vista clinical trials in its X-linked retinitis pigmentosa (XLRP) program and its ongoing Phase I/II clinical trials in its Achromatopsia (ACHM) program, as well as preclinical programs, manufacturing facility investments, working capital, and general corporate purposes that include scheduled payments under its term loan with Hercules Capital.
Atara Biotherapeutics (ATRA)
Atara shares plunged 55% from $8.66 to $3.89 on Wednesday, a day after the company acknowledged it lacked sufficient data to conclude how accurately six-month Expanded Disability Status Scale (EDSS) improvement data could predict confirmed EDSS improvement at 12 months—the primary endpoint for the company’s Phase II EMBOLD trial (NCT03283826).
EMBOLD is designed to assess Atara’s ATA188, a T-cell immunotherapy targeting EBV antigens, in patients with progressive forms of multiple sclerosis.
The acknowledgement followed an interim analysis by the trial’s Independent Data and Safety Monitoring Committee (IDSMC). At the time, EDSS data existed on 34 patients evaluable at six months and 15 patients at 12 months (across both placebo and active groups randomized 1:1).
Jakob Dupont, MD, Head of Global Research & Development at Atara, stated that topline results from EMBOLD are planned to be shared in October 2023 “at an appropriate forum.”
ContraFect (CFRX)
ContraFect shares shriveled 81% in early trading Thursday, to 54.15 cents a share (as of 10:30 am ET) from Wednesday’s close of $2.845, the day after the company announced it was halting patient enrollment in its Phase III DISRUPT trial (NCT04160468) at the recommendation of the study’s Data Safety Monitoring Board (DSMB).
“The conditional power of the study was below the pre-specified threshold for futility,” ContraFect said in a statement.
ContraFect said it planned to disclose details regarding the development of exebacase “following completion of its own analysis of the accrued study data.”
The company said the DSMB’s recommendation was based on an analysis of the clinical response rate at day 14—the study’s primary efficacy endpoint—in 84 patients, or approximately 60% of the total planned methicillin-resistant Staphylococcus aureus (MRSA) population with bacteremia, including right-sided endocarditis.
DISRUPT is designed to assess the efficacy and safety of exebacase in approximately 350 patients with complicated S. aureus bacteremia, including right-sided endocarditis. The primary efficacy endpoint of the randomized, double-blind, placebo-controlled clinical study is clinical response at Day 14 in patients with MRSA bacteremia, including right-sided endocarditis.
Secondary endpoints include clinical response at Day 14 in the All S. aureus patients (MRSA and methicillin-sensitive S. aureus (MSSA), 30-day all-cause mortality in MRSA patients, and clinical response at later timepoints, ContraFect added.
“This disappointing news reflects the long history of difficulties in treating life-threatening infections like MRSA bacteremia in patients with heterogeneous co-morbidities, and who are in need of immediate life-saving treatments,” stated Roger J. Pomerantz, MD, ContraFect’s President, CEO, and Chairman.
XORTX Therapeutics (XRTX)
XORTX shares zoomed 47% on Wednesday, from $1.23 to $1.81, after the company announced positive top-line results from Part 1 of the three-part Pharmacokinetics Bridging Study–XRX-OXY-101.
XORTX said the results showed a substantial increase in oral bioavailability of two versions of XORTX’s proprietary oxypurinol formulation compared to a control formulation.
Part 1 was designed to help XORTX select the clinical dose and future oral dosing formulation for the company’s planned Phase III registration trial of XRx-008 in autosomal dominant polycystic kidney disease (ADPKD).
“We look forward to the initiation of dosing of Part 2 of the XRX-OXY-101 this week,” XORTX CEO Allen Davidoff, PhD, said in a statement.