Source : 'Scrip Intelligence'
Roche Holding AG has a long history in infectious diseases, including the antibiotics Rocephin and Bactrim as well as the influenza antivirals Tamiflu and Xofluza, and the company has put its expertise to use in COVID-19 through testing of its arthritis biologic Actemra – though results have been mixed – and through partnerships for the development of novel treatments. Ultimately, Roche believes that it likely will take combinations of multiple drugs to mount the most effective attack against the novel coronavirus.
Patrick Schleck, global head of partnering for immunology and infectious diseases at Roche and Genentech, Inc. , described his group’s approach to COVID-19 in a recent interview with Scrip. Roche wants to bring forward truly innovative medicines against the virus and sees partnering as an important means for accessing innovation.
“Broadly speaking, about half of our pipeline and almost 40% of our revenue comes from partnered molecules, and actually 15 of our last 20 new medicines that we've launched across Roche were partnered molecules,” Schleck said.
Roche’s partnering strategy in infectious diseases is focused on three pillars: respiratory viruses, now including COVID-19; multidrug-resistant bacterial infections, with emphasis on treating hospitalized patients with severe infections; and hepatitis B, where the company now has four molecules in early clinical development.
Roche has entered into two COVID-19 partnerships to date. The first is with Regeneron Pharmaceuticals, Inc. with a focus on developing and manufacturing enough supply of the firm’s antibody cocktail REGN-COV2 for the treatment of COVID-19 patients around the world. () Regeneron is seeking emergency use authorization for REGN-COV2 in the treatment of mild-to-moderate cases of COVID-19 in the outpatient setting. ()
The second COVID-19 collaboration is for the development, manufacturing and distribution of Atea Pharmaceuticals, Inc.’s direct-acting antiviral AT-527, which is expected to move into Phase III early next year in the treatment of hospitalized patients. Roche and Atea anticipate that AT-527 could be used more broadly than biologics – even prophylactically for health care workers and others at high risk of exposure to SARS-CoV-2 – since the drug is an oral small molecule that could be mass produced more easily.
From its own portfolio, Roche has tested the interleukin-6 (IL-6) inhibitor Actemra (tocilizumab) in hospitalized adults with severe COVID-19 pneumonia and found that it did not meet the primary endpoint of improved clinical status or secondary endpoint of reduced mortality in the Phase III COVACTA clinical trial. () The likelihood of progression to mechanical ventilation or death in hospitalized patients with COVID-19 pneumonia was reduced for Actemra-treated participants in the Phase III EMPACTA trial, but there was no benefit on mortality relative to placebo. ()
The Phase III REMDACTA study that Roche launched in May is testing Actemra in combination with Gilead Sciences, Inc.’s antiviral Veklury (remdesivir) in hospitalized COVID-19 patients with severe pneumonia. () Roche also has an early research program under way internally to identify new treatments for the novel coronavirus.
“We’re big believers that we need to have a multi-factorial approach to try to help make an impact on this virus – that no one thing alone is going to be enough,” Schleck said. “There's efforts we're doing now with Actemra and other programs internally for immunomodulators to try to treat advanced disease for the hospitalized patients that have really overactive immune systems.”
“The strategic intent and the focus on Regeneron and neutralizing antibodies was to explore that modality, as you know, which is being tested in multiple different trials spanning hospitalized patients, outpatients and even in preventative settings to explore where a neutralizing antibody might help patients,” he continued.
“With Atea, it was a vision for how can an oral be different for patients and maybe allow for easier treatment at home to really access patients broadly, to help treat them early before they get too sick, before they progress to the hospital, and have the benefits of a simple oral you could take at home that helps reduce the impact on health systems,” Schleck said. “And, hopefully, we can manufacture at a very broad scale as a small molecule to help distribute around the world.”
The idea of both partnerships and potential additional collaborations was to bring Roche’s expertise and ideas to partners that may need help advancing their development programs and getting their drugs to patients faster.
Roche’s partnerships with Regeneron and Atea are the company’s most recent infectious disease deals, but the big pharma continues to seek out collaborators across its three pillars – respiratory diseases, antibiotics and hepatitis B.
During the past two years, Roche has negotiated 14 deals in the infectious disease space, including a collaboration announced in March with Forge Therapeutics Inc. for the development of novel antibiotics known as LpxC inhibitors for drug-resistant lung infections, with a focus on Gram-negative pathogens such as Pseudomonas aeruginosa. ()
The company partnered with Dicerna Pharmaceuticals, Inc. in November for the development of a short interfering RNA (siRNA) therapeutic to treat hepatitis B in a deal worth $200m up front. ()
“We see a lot of interest in partnering continued from our side in hepatitis B,” Schleck said. “As Roche progresses our pipeline of molecules into the clinic, we're eager to think about combination therapies and how can we combine maybe direct-acting antivirals together with immune stimulants to try to deliver cures, and really eliminate the virus. There's a lot of appetite and interest on our side in looking at novel approaches and novel mechanisms that might well pair with medicines that we have.”
“And antibiotics, I think that commitment is also still highly engaged and highly interesting on our side to explore, trying to find truly novel antibiotics to get to market,” he continued. “We haven't delivered a new class of antibiotics for patients in 50 years, so the needs and appetite on our side to continue to look for truly novel mechanisms, things that could be really different for patients, is quite high.”
Immunology deals by Schleck’s partnering group also continue with a broad focus on autoimmune and inflammatory diseases and within that a particular interest in respiratory and gastrointestinal diseases.
Roche recently announced its purchase of Enterprise Therapeutics Ltd for £75m ($97m) up front to acquire a first-in-class drug for cystic fibrosis and other muco-obstructive diseases. ()
The company said in September that it agreed to pay €380m up front for Inflazome Ltd., which has a portfolio of NLRP3 antagonists for inflammatory diseases. ()
“Similarly to infectious diseases, we see a lot of exciting stuff coming from biotech [in immunology], and we're eager to access that innovation wherever it may come from,” Schleck said. ()
By Mandy Jackson