Although details are yet to come, Equillium Inc.’s chief medical officer, Krishna Polu, told BioWorld that the company will move “urgently and expeditiously” to set up another experiment testing itolizumab in COVID-19 now that Bangalore, India-based partner Biocon Ltd. has unveiled positive phase II results with the CD6-targeting agent.
Shares of Equillium (NASDAQ:EQ) closed at $26.50, up $23.31, or 731%, after trading as high as $27.05. “We recognize we have to do a robust study,” said Bruce Steel, CEO of the La Jolla, Calif.-based firm. Talks with the FDA about design come next, but the clinical bid will “very likely include sites outside the U.S.,” where the need is high and where there is “somewhat less competition for patients,” he said. “We are still formulating our plans for that.” Meanwhile, the Drugs Controller General of India has granted restricted emergency use of itolizumab for the treatment of cytokine release syndrome (CRS) in COVID-19 patients with moderate to severe acute respiratory distress syndrome (ARDS).
Biocon conducted a randomized, controlled, open-label study at four hospitals in India, enrolling 30 hospitalized COVID-19 patients with moderate to severe ARDS. Twenty patients were randomized to receive itolizumab plus best supportive care, while 10 got best supportive care alone. The primary endpoint was mortality at one month – “exactly the kind of endpoint described in [FDA] guidance documents” for such research, Polu noted. In the itolizumab arm there were no deaths and all patients have recovered; in the control arm three patients died and the remainder are back on their feet. The mortality benefit observed in the itolizumab arm was statistically significant and, consistent with the observed clinical improvement, patients on itolizumab also turned up meaningful drops in inflammatory cytokines such as IL-6 and TNF-alpha.
U.S. regulators, like others around the world, have streamlined rules to move development along briskly. “They’re turning around their [IND] reviews in general, from what we understand, within two weeks,” Polu said. Rules inspired by COVID-19 offer “the potential to move straight into a registration-type study,” he said. Equillium holds rights to itolizumab, which was originally developed by Cuba’s Center for Molecular Immunology, in the U.S., Canada, Australia and New Zealand. The drug is in the works also for acute graft-vs.-host disease (phase Ib/II, with first data from the trial known as Equate due in the second half of this year), uncontrolled asthma (phase Ib) and lupus nephritis (LN, phase Ib). Late last year, the FDA granted fast track status in LN.
Steel said the partnership with a powerhouse drugmaker such as Biocon provides critical oomph in the COVID-19 pandemic. The firm is the fourth-largest supplier of insulin, and has a collaboration with Hertfordshire, U.K.-based Mylan NV for biosimilars to Herceptin (trastuzumab, Roche Holding AG) and Neulasta (pegfilgrastim, Amgen Inc.). “There is actually quite a bit of risk in manufacturing biologics – people often overlook that,” he said. “When we started the company, Biocon had already completed the CMC and scale-up” of itolizumab. “We have drug product on hand in the U.S. sufficient to supply the next clinical study that needs to be conducted,” and Biocon is likely to prioritize its efforts in order to pump out more, he said. “They have capacity but, clearly, they can’t drop everything else,” and Equillium will learn more in the weeks ahead.
Insight from Biocon suggests “a larger experience that goes beyond the trial results in India,” Polu said. Wainwright analyst Raghuram Selvaraju affirmed as much, and sees “tantalizing implications” in the trial results. “Beyond the scope of the 30-patient trial, over 150 patients have been treated with itolizumab in the Indian states of Maharashtra, Gujarat and Uttar Pradesh,” he wrote in a report. “It was particularly interesting for us to learn that Indian physicians who have been infected with COVID-19 are starting to request treatment with this drug if they experience difficulty in recovering. Various practitioners who had experience with utilization of itolizumab evinced enthusiasm over the drug's mechanism of action,” which may hold “key advantages” over alternative treatments that block only IL-6. “For those patients experiencing CRS or ARDS, the option of itolizumab treatment could prove lifesaving,” in his view. The drug is already approved in India under the brand name Alzumab for psoriasis.
Other stock-boosting COVID-19 news, though the rise was nowhere near as dramatic, involved Gaithersburg, Md.-based Altimmune Inc., shares of which (NASDAQ:ALT) closed at $25, up $2.65, or 12%, on positive results from the preclinical studies of its intranasal COVID-19 vaccine candidate called AdCOVID. The studies, carried out in collaboration with the University of Alabama at Birmingham, showed strong serum neutralizing activity and potent mucosal immunity in the respiratory tract. Altimmune plans to start manufacturing AdCOVID, advancing the candidate to a phase I safety and immunogenicity study in the fourth quarter of this year.
Roth analyst Yasmeen Rahimi opined in a June 3 report that “the totality of literature concerning SARS-CoV-2 indicates that the nasal cavity (upper respiratory tract) as the key hotspot for viral entry and infection, and with this observation comes the potential for Altimmune’s intranasal vaccine AdCOVID to bring strong differentiation in the crowded prophylactic vaccine space.”