gr-cis.com

South Korea’s Celltrion has joined the many pharma companies fighting the COVID-19 coronavirus outbreak, saying it is working on an antibody-based antiviral and a self-testing diagnosis kit providing results within 15-20 minutes.

Best known as a manufacturer of biosimilars – which are near-copies of previously approved biologic drugs – Celltrion is turning its hand to producing therapies against the virus that has killed thousands of people and disrupted economies across the world.

The company said it has been selected as a preferred developer for a monoclonal antibody project to treat and prevent COVID-19 by the Korea Centers for Disease Control.

Celltrion has built a library of antibodies from the recovered patients in Korea, which are thought to be involved in neutralising the virus and may contribute to recovery from COVID-19.

Korea was one of the first countries affected by the pandemic and is screening the library to identify antibodies that are most effective at neutralising the SARS-CoV-2 virus that causes the disease.

Once identified these will form the basis of an antiviral treatment, with pre-clinical and clinical trials planned around Q3 this year.

Celltrion is going further and planning a ‘super antibody’ that can attach and neutralise all coronavirus related strains, such as those causing COVID-19 and SARS, enabling further protection against unforeseen or unexpected mutations.

This could contribute towards preparedness for potential future pandemics, Celltrion said.

Japan’s Takeda is also working on a therapy based on antibodies from previously treated patients, although this is based on harvesting the blood plasma of recovered patients for the antibodies, rather than producing a genetically engineered monoclonal antibody like Celltrion.

While Takeda’s approach is proven and will require less scrutiny from regulators, Celltrion’s approach could allow it to scale up production without the need for large numbers of donors.

Diagnostic test

Celltrion also aims to launch a rapid self-testing diagnostic kit in the summer of this year, focusing on the gene that codes for the spike (S) protein that allows the virus to enter host human cells.

The kit is designed to show results within 15-20 minutes, with optimised sensitivity, specificity and improved accuracy features. Once it has gained a CE mark, the rapid self-testing diagnostic kit will become available throughout Europe through Celltrion Healthcare.

Celltrion plans to apply for device authorisation from the FDA in the US and other regulatory authorities after acquiring relevant data.

Days after Swiss pharma giant Roche began shipping hundreds of thousands of its recently-approved COVID-19 test to laboratories in the United States, the company has initiated a late-stage trial assessing its rheumatoid arthritis drug Actemra in patients who have severe COVID-19 caused pneumonia.

This morning, Roche said it was launching a Phase III trial of Actemra (tocilizumab) plus standard-of-care in hospitalized patients with this type of pneumonia. Following treatment, patients in the trial will be followed for 60 days post-randomization, and an interim analysis will be conducted to look for early evidence of efficacy, Roche said. This is the first global study of Actemra in this setting and the company said it anticipates enrolling patients beginning in April. The primary and secondary endpoints include clinical status, mortality, mechanical ventilation and intensive care unit (ICU) variables, Roche said.

Actemra is an IL-6 inhibitor. The IL-6 protein triggers the body’s immune and inflammatory response to fight infections. But, in the case of those patients where their immune system overreacts, inhibiting IL-6 could keep the body from attacking itself. As COVID-19 continues to spread across the globe, there have been reports that some physicians in China have been using Actemra in a number of patients who are showing overactive immune responses to the novel coronavirus. The immune systems of these patients have been attacking healthy tissues and organs, including their lungs. The Chinese physicians prescribed Actemra in order to calm those immune responses. Last week, Regeneron and Sanofi announced they would be testing their IL-6 inhibitor Kevzara as a potential treatment following these reports. Citing reports from that country, Regeneron Chief Scientific Officer George Yancopoulos told reporters that patients who received the Roche treatment “got out of death’s bed and walked out of the hospital.” Actemra has now been included in diagnosis and treatment plan for COVID-19 issued by China’s National Health Commission.

Levi Garraway, Roche’s chief medical officer and head of Global Product Development said the company is initiating the trial in order to gain a better understanding of Actemra on these patients with COVID-19 pneumonia. Garraway said the company intends to get the trial up and running as quickly as possible and will share the results as soon as possible.

Roche said there have been several independent trials launched that are exploring the safety and efficacy of Actemra in this setting. However, the company said its trial is vital because there are no well-controlled studies and limited published evidence on the safety or efficacy of Actemra in the treatment of the patients suffering from COVID-19.

Pfizer had a good day Wednesday with the announcement of positive results from two Phase III trials, one in moderate to severe atopic dermatitis and one in pneumococcal disease.

In pneumococcal disease, Pfizer announced top-line results from a late-stage study that evaluated the safety and immunogenicity of its 20-valent pneumococcal conjugate vaccine candidate in adults who had not previously been vaccinated against pneumococcal disease. The company said the study of 20vPnC hit the mark with primary immunogenicity objectives of non-inferiority for the 20 serotypes included in adults 60 years of age at one month following vaccination.

Pfizer’s 20vPnC vaccine candidate includes 13 serotypes already included in the company’s approved vaccine, Prevnar 13. The seven new serotypes included in the new vaccine are global causes of invasive pneumococcal disease and are associated with high case-fatality rates, antibiotic resistance, and/or meningitis, the company said. Together, the 20 serotypes included in 20vPnC are responsible for the majority of currently circulating pneumococcal disease in the U.S. and globally, Pfizer said.

Pfizer added that the study also met its goal for all serotypes in common with licensed Prevnar 13 (pneumococcal 13-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) and six of the seven additional serotypes when compared to a licensed pneumococcal polysaccharide vaccine. The company did note that one of the new seven serotypes missed non-inferiority criteria by a small margin.

In addition to the primary immunogenicity objectives for the older patient population, secondary objectives for adults 18-59 were non-inferior for all 20 serotypes when compared to results for the group aged 60-64, Pfizer said.

Safety objectives were also met in the study, which Pfizer said demonstrated that the vaccine was comparable to licensed pneumococcal vaccines. Based on prior discussions with regulators, Pfizer said these data are expected to meet licensure criteria. The company plans to present the data from this trial at a future conference.

Kathrin Jansen, senior vice president and head of vaccine research and development at Pfizer, said they are encouraged by the results from the study and remain on track to file for approval of 20vPnC with the U.S. Food and Drug Administration by the end of 2020. Jansen said 20vPnC builds on a “well-established and trusted foundation of pneumococcal conjugate experience and science” that Pfizer has established over the course of two decades.

“The results from this pivotal study provide evidence that the 20vPnC vaccine is expected to have a comparable safety profile and likely be as effective as Prevnar 13 in helping prevent invasive pneumococcal disease and pneumonia due to the 13 serotypes in Prevnar 13, and also effective against disease due to the seven additional pneumococcal serotypes in adults 18 years of age or older,” Jansen said in a statement.

In atopic dermatitis, Pfizer said its Phase III JADE COMPARE study evaluating abrocitinib, an investigational oral once-daily Janus kinase 1 (JAK1) inhibitor, in adults who were on background topical therapy met its co-primary efficacy endpoints. Trial results showed that the percentage of patients achieving each co-primary efficacy endpoint at Week 12 was statistically superior with both doses of abrocitinib than with placebo, the company noted. The study also included an active control arm, dupilumab, a biologic treatment administered by subcutaneous injection, compared with placebo.

With data from the JADE COMPARE trial, as well as results from the pivotal MONO-1 and MONO-2 trials, Pfizer plans to seek regulatory approval of abrocitinib in this setting later this year.

Michael Corbo, chief development officer of Inflammation & Immunology at Pfizer Global Product Development, said the addition of an active control like dupilumab was important in order to gain a better understanding of the significance of abrocitinib. He added that the company is encouraged by the positive data from this trial.

While Pfizer saw positive results from these trials, the company also announced Wednesday that it was postponing its Investor Day set for March 31 due to concerns of the coronavirus. The company intends to reschedule the event but has not yet set a date. Pfizer will work within the context of appropriate guidance from health authorities to determine a future date.

• More than one-third of the SERENITY I & II patients have been dosed, including over 100 bipolar patients
• On track to report topline data from both studies in mid-2020

NEW HAVEN, Conn., March 19, 2020 (GLOBE NEWSWIRE) — BioXcel Therapeutics, Inc. (“BTI” or “Company”) (Nasdaq: BTAI), a clinical-stage biopharmaceutical company utilizing artificial intelligence to identify improved therapies in neuroscience and immuno-oncology, today announced that more than one-third of the patients in the Phase 3 SERENITY trials have been enrolled and treated. To date, the company has not observed a change in enrollment rates resulting from the COVID-19 pandemic, and currently maintains previous guidance that SERENITY I & II are expected to be completed by mid-year 2020.

“Despite the current situation with COVID-19, we remain on track with the enrollment of our SERENITY studies,” stated Vimal Mehta, Chief Executive Officer of BTI. “Up to now, all schizophrenia and bipolar patients enrolled have successfully self-administered the BXCL501 treatment, guided by a healthcare provider, and the trials seem to be progressing well. We are optimistic that enrollment rates will continue to stay consistent with previous weeks and are looking forward to sharing topline results in the middle of this year.”

The SERENITY studies are randomized, double-blinded, placebo-controlled, adaptive trials of up to 750 patients, 18 to 75 years of age. SERENITY I is enrolling patients with agitation associated with schizophrenia, with each arm receiving BXCL501 at 120 micrograms, 180 micrograms or placebo, respectively. SERENITY II is evaluating patients with agitation associated with bipolar disorder, also in three arms receiving BXCL501 at 120 micrograms, 180 micrograms or placebo, respectively. The primary endpoint of the trials is reducing acute agitation measured by the Positive and Negative Syndrome Scale, examining the Excited Component (“PEC”) change from baseline compared to placebo. A key secondary endpoint includes determining the earliest time where an effect on agitation is apparent as measured by the change from baseline in PEC total score.

About Agitation in Neuropsychology

Agitation is a common and difficult to manage symptom associated with a number of psychiatric conditions, including schizophrenia and bipolar disorder. It is estimated that approximately 19 million people are at risk of agitation, and 8.3 million in the U.S. suffer from agitation each year, costing approximately $40 billion annually in treatment related expenses. Early identification and prompt intervention to relieve agitation are essential to avoid symptomatic escalation and emergence of aggression. Recent consensus guidelines emphasize the need for non-coercive management strategies to protect the therapeutic alliance between patients and their healthcare providers—an alliance that is critical for the effective management of chronic psychiatric conditions. A non-invasive therapy that causes rapid symptom relief and de-escalates agitation may be necessary to avoid the costly and traumatic use of coercive techniques, like physical restraint and seclusion, which require admission and prolonged hospitalization.

About BXCL501

BXCL501 is an investigational proprietary sublingual thin film of dexmedetomidine, a selective alpha-2a receptor agonist for the treatment of acute agitation. BTI believes that BXCL501 directly targets a causal agitation mechanism, and the Company has observed anti-agitation effects in multiple clinical studies across multiple neuropsychiatric indications. BXCL501 has been granted Fast Track Designation by the U.S. Food and Drug Administration for the acute treatment of agitation.

A Phase 1b safety and efficacy study of BXCL501 in patients with schizophrenia yielded positive dose-response data. BXCL501 is being evaluated in the SERENITY program, consisting of two Phase 3 studies for the acute treatment of agitation in patients with schizophrenia (SERENITY I) and bipolar disorder (SERENITY II). BXCL501 is also being evaluated in a Phase 1b/2 trial (TRANQUILITY) for the treatment of agitation associated with dementia, and the Company is preparing to initiate a Phase 1b/2 study (RELEASE) of BXCL501 for the treatment of opioid withdrawal symptoms.

About BioXcel Therapeutics, Inc.:

BioXcel Therapeutics, Inc. is a clinical-stage biopharmaceutical company utilizing artificial intelligence to identify improved therapies in neuroscience and immuno-oncology. BTI’s drug re-innovation approach leverages existing approved drugs and/or clinically evaluated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indices. BTI’s two most advanced clinical development programs are BXCL501, an investigational sublingual thin film formulation in development for acute treatment of agitation resulting from neuropsychiatric disorders, and BXCL701, an investigational orally administered systemic innate immunity activator in development for treatment of a rare form of prostate cancer and for treatment of pancreatic cancer in combination with other immuno-oncology agents. For more information, please visit http://www.bioxceltherapeutics.com.

Johnson & Johnson has announced that DePuy Synthes, which produces cementless hip implants, has been informed of the European CE mark on its new Bi-Mentum Dual Mobility System for use in patients with a higher risk of dislocation.

Bi-Mentum features a standard femoral head articulating within a large polyethylene liner which then swivels within a metal shell. The system is designed to reduce the risk of dislocation, which can impact patient satisfaction and result in later revision costs. 

More than three million hip arthroplasties have been registered in Europe since 1975. The incidence of instability caused by dislocation after Total Hip Arthroplasty (THA) in the primary and revision setting has been reported to be as high as 7% and 25%, respectively. Instability can have a significant impact on patients’ quality of life and mobility. In addition to the burden of repeat surgeries, dislocation can also impact costs in a resource-constrained environment. In fact, the surgical treatment of a dislocating THA can raise the cost of hip replacement by 342%.

Aaron Villaruz, vice president and global platform leader for hips at Depuy Synthes, said: “With an increasing number of patients undergoing hip replacement surgery, surgeons need to address a broader range of surgical needs to help their patients stay active and get on with their lives. Securing the CE Mark on BI-MENTUM enables us to better serve our customers and patients across Europe with a solution that is designed to make a continued difference in hip replacement.

In 2018, DePuy Synthes announced a distribution agreement with SERF (Société d’Etude, de Recherche et de Fabrication), an orthopaedics company with experience in dual-mobility technology. DePuy Synthes is now bringing the latest dual-mobility acetabular cups, identical to Serf dual-mobility cups, under its own brand name, Bi-Mentum Dual Mobility. This clinically proven dual-mobility technology has achieved a track record of 100% cup survivorship at 10 years and also an implant milestone of 165,000 cups since 2007.

Bi-Mentum, currently available in the United States, is scheduled to be available in select European markets in April 2020. This dual-mobility system integrates with DePuy Synthes hip stems, including the market-leading Corail Hip System with more than 2.5 million implantations to date. Sharing in the French design legacy, Corail is backed by registries of peer-reviewed clinical evidence documenting more than 350,000 Corail implantations with a 93.7% survivorship rate at 30 years.

The market for 5G cellular connections in manufacturing is expected to reach $10.8 billion by 2030, at a Compound Annual Growth Rate (CAGR) of 187%, according to global tech market advisory firm, ABI Research.

The current Industry 4.0 digitalisation discourse centres around conventional financial metrics (e.g., return on investment, net profit, and cash flow) as the yardstick to measure 5G and edge computing effectiveness. But these metrics are financial measurements to gauge profit and do not lend themselves to the factory floor.

These three measurements enable Industry 4.0 partners (e.g., ABB, Bosch, Siemens) to institute a direct connection between the 5G’s utility and what takes place on the factory floor. In turn, they will be able to use that connection to find a logical relationship between daily plant operations and the overall company’s performance. Only then, will Industry 4.0 verticals have a basis for knowing the real benefit of 5G and edge computing

Don Alusha, senior analyst at ABI Research, said: “But, to capture the value at stake, ecosystem stakeholders will first need to evaluate how to measure the impact of 5G and edge deployments. Therefore, Industry 4.0 ecosystem entities must consider an alternative set of measurements that look at how 5G and edge deployments aid manufacturing establish operational rules to run a plant. They are throughput, inventory and operational expense for the incoming flow of capital, for capital located inside, and for capital going out, respectively.

“Furthermore, equally important is the ability to measure risk when looking to adopt 5G and edge technology assets. Discussions on new technology adoption have always been based on an assessment of risk and reward. If the reward is truly compelling, adopters will take the risk. 5G and edge offer unprecedented commercial opportunities, but they inherently constitute new technologies and therefore there is a risk attached.”

Continued attempts to keep up productivity growth, increase process automation to meet changing client demands, and the need to establish a reliable supply-chaining that spans multiple geographies are forcing manufacturers to be more flexible.

CAMBRIDGE, Mass. and TARRYTOWN, N.Y., March 16, 2020 /PRNewswire/ — Sanofi and Regeneron Pharmaceuticals, Inc. today announced they have started a clinical program evaluating Kevzara^® (sarilumab) in patients hospitalized with severe COVID-19. Kevzara is a fully-human monoclonal antibody that inhibits the interleukin-6 (IL-6) pathway by binding and blocking the IL-6 receptor. IL-6 may play a role in driving the overactive inflammatory response in the lungs of patients who are severely or critically ill with COVID-19 infection. The role of IL-6 is supported by preliminary data from a single-arm study in China using another IL-6 receptor antibody.

This U.S.-based trial will begin at medical centers in New York, one of the epicenters of the U.S. COVID-19 outbreak, and will assess the safety and efficacy of adding Kevzara to usual supportive care, compared to supportive care plus placebo. The multi-center, double-blind, Phase 2/3 trial has an adaptive design with two parts and is anticipated to enroll up to 400 patients. The first part will recruit patients with severe COVID-19 infection across approximately 16 U.S. sites, and will evaluate the impact of Kevzara on fever and patients’ need for supplemental oxygen. The second, larger part of the trial will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.

“At Sanofi, we are taking a leading role in addressing the global challenge of COVID-19 disease.  We believe that there is scientific evidence to suggest that Kevzara may be a potentially important treatment option for some patients, and this trial will provide the well-controlled, rigorous scientific data we need to determine if IL-6 inhibition with Kevzara is better than current supportive care alone.  Additionally, we expect to rapidly initiate trials outside the U.S. in the coming weeks, including areas most affected by the pandemic such as Italy,” said John Reed, M.D., Ph.D., Sanofi’s Global Head of Research and Development.   “In addition to Kevzara, Sanofi Pasteur, the vaccines global business unit of Sanofi, is leveraging previous development work for a SARS vaccine as part of our goal to quickly develop a COVID-19 vaccine.”

Scientists have preliminary evidence that IL-6 may play a key role in driving the inflammatory immune response that causes acute respiratory distress syndrome (ARDS) in patients critically ill from COVID-19.  Initial non-peer reviewed results from a single-arm, 21-patient Chinese trial found COVID-19 patients experienced rapidly reduced fevers and 75% of patients (15 out of 20) reduced their need for supplemental oxygen within days of receiving another IL-6 receptor antibody (tocilizumab). Based on these results, China recently updated its COVID-19 treatment guidelines and approved the use of that IL-6 inhibitor to treat patients with severe or critical disease.

“To initiate this trial quickly, Regeneron and Sanofi have worked closely with the U.S. Food and Drug Administration and the Biomedical Advanced Research and Development Authority, otherwise known as the FDA and BARDA ,” said George D. Yancopoulos, M.D., Ph.D., Co-founder, President and Chief Scientific Officer of Regeneron. “Data from China suggest that the IL-6 pathway may play an important role in the overactive inflammatory response in the lungs of patients with COVID-19. Despite this encouraging finding, it’s imperative to conduct a properly designed, randomized trial to understand the true impact.  Our trial is the first controlled trial in the U.S. to evaluate the effect of IL-6 inhibition prospectively in COVID-19 patients. In addition to our Kevzara program, Regeneron is also rapidly advancing a novel antibody cocktail for the prevention and treatment of COVID-19, which we hope to have available for human testing this summer. Both of these programs are made possible by our unprecedented end-to-end antibody discovery, development and manufacturing technologies, starting with our proprietary VelocImmune human antibody mouse, and incorporating our associated rapid manufacturing technologies designed to select and produce the best neutralizing antibodies. Collectively, these technologies expedite a typically years-long process into a matter of months. This same technology was applied to the Ebola virus, where our therapy, REGN-EB3, was shown to dramatically improve survival in infected patients last year.”

In late 2019, Regeneron and Sanofi announced their intent to simplify the joint collaboration for Kevzara, which is expected to be finalized in the first-quarter of 2020. The companies will continue to collaborate on COVID-19 and other related ARDS development, with Regeneron leading U.S.-based work and Sanofi leading work outside of the U.S.

The use of Kevzara to treat the symptoms of COVID-19 is investigational and has not been fully evaluated by any regulatory authority.

About the Trial
This Phase 2/3, randomized, double-blind, placebo-controlled trial uses an adaptive design to evaluate the safety and efficacy of Kevzara in adults hospitalized with serious complications from COVID-19. To enter the trial, patients must be hospitalized with laboratory-confirmed COVID-19 that is classified as severe or critical, or who are suffering from multi-organ dysfunction. All patients must have pneumonia and fever. After receiving the study dose, patients will be assessed for 60 days, or until hospital discharge or death.

In the Phase 2 part of the trial, patients will be randomized 2:2:1 into three groups: Kevzara high dose, Kevzara low dose and placebo. The primary endpoint is reduction of fever and the secondary endpoint is decreased need for supplemental oxygen.

The Phase 2 findings will be utilized in an adaptive manner to determine transition into Phase 3, helping to determine the endpoints, patient numbers and doses. The second, larger part of the trial will evaluate the improvement in longer-term outcomes including preventing death and reducing the need for mechanical ventilation, supplemental oxygen and/or hospitalization.

If the trial continues with all three treatment arms to the end, it is expected to enroll approximately 400 patients, depending on the status of the COVID-19 outbreak and the proportion of patients with severe COVID-19 and high levels of IL-6.

About Kevzara® (sarilumab) Injection
Kevzara was jointly developed by Sanofi and Regeneron under a global collaboration agreement.  Kevzara is a fully-human monoclonal antibody. Kevzara binds specifically to the IL-6 receptor, and has been shown to inhibit IL-6-mediated signaling. IL-6 is a signaling protein produced in increased quantities in patients with rheumatoid arthritis and has been associated with disease activity, joint destruction and other systemic problems. It is also being investigated for its ability to reduce the overactive inflammatory immune response associated with COVID-19. 

Denmark’s Novo Nordisk paused three clinical trials of concizumab over safety issues. The trials are evaluating the drug for hemophilia A and B. No more patients will be enrolled in the trials and current treatment “will cease” while they determine the risks and plans for the trials.

Two of the trials were the EXPLORER 7 and EXPLORER 8 Phase III trials. The other was the Phase II EXPLORER 5 trial. The company indicates the decision was based on non-fatal thrombotic events in three patients enrolled in the Phase III program. The company and an independent Data Monitoring Committee are evaluating the data to determine if the problems are linked to the drug.

“While it is disappointing to pause the trials, patient safety is of utmost important to Novo Nordisk—both for those taking part in our clinical trials and those who use our products on a daily basis,” said Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo Nordisk. “Together with relevant authorities, we will now carefully evaluate all available data and decide how to best move forward.”

Hemophilia is an inherited blood disorder characterized by low levels of clotting factor proteins that help blood clot appropriately. When these proteins are at low levels, patients’ blood does not clot effectively, which can lead to serious health issues when bleeding happens. The two most common forms of hemophilia are hemophilia A and B, named after the specific clotting factors that the patients are missing or are in insufficient amounts.

Thrombosis refers to a blood clot, which can lead to stroke or other health problems.

Concizumab is a monoclonal antibody against Tissue Factor Pathway Inhibitor (TFPI).

EXPLORER 7 and EXPLORER 8 were designed to demonstrate that concizumab can prevent bleeds in the body and the drug’s safety. Patients who typically only take medicine to treat bleeds on demand were randomized to either receive concizumab at the beginning of the study while the other group continued to receive their normal therapy and received concizumab after six months. The drug was injected by the patient every day subcutaneously via a pen-injector.

EXPLORER 5, the Phase II trial, involved 36 patients, and was being conducted in Asia, Europe and the U.S. The treatment duration is 24 weeks in the main phase and 52 weeks in the extended phase.

Novo Nordisk is a major player in the diabetes market but has been aggressively moving into hemophilia. The company launched Esperoct in the U.S. for hemophilia A in February 2020. Esperoct is a recombinant extended half-life factor VIII replacement therapy. It was approved by the U.S. Food and Drug Administration (FDA) in 2019 based on five multinational trials, which included 270 patients.

“At Novo Nordisk, we have a longstanding commitment to the hemophilia community, beginning with the development of our first recombinant factor therapy more than 30 years ago,” said Pia D’Urbano, corporate vice president, Biopharmaceuticals, Novo Nordisk, at the time of launch. “We recognize that people with rare bleeding disorders need multiple therapy options and are proud to now make Esperoct available as a new treatment option for those living with hemophilia A, the most common form of the chronic bleeding disorder.”

In October 2019, Novo Nordisk and Cambridge, Massachusetts-based bluebird bioentered a collaboration deal to develop next-generation genome editing therapies for genetic diseases, including hemophilia. It is a three-year pact, with the top priority to develop a gene therapy for hemophilia A. It will leverage bluebird’s mRNA-based megaTAL technology that is used to silence, edit, or insert genetic components.

Eli Lilly’s Olumiant is facing tough competition in its approved rheumatoid arthritis indication, but could take the lead in alopecia areata (AA), a common cause of hair loss.

The FDA has granted Lilly a breakthrough designation (BTD) for JAK inhibitor Olumiant (baricitinib) in AA, an autoimmune disease that typically first manifests in childhood and leads to loss of hair in patches on the scalp, face and sometimes other areas of the body. In extreme cases it can lead to loss of all head and body hair.

There are no approved treatments in the US for this type of alopecia, which affects around 6.8 million people in the US alone. At the moment it can only be managed using powerful corticosteroid drugs, which suppress the immune system but can have serious side effects if used long-term.

The BTD for Olumiant – originally developed by Incyte – has been granted on the strength of phase 2 results from an ongoing 725-patient phase 2/3 trial called BRAVE-AA1, which compared 2 mg and 4 mg doses of the drug with placebo in adults with severe or very severe AA.

The phase 3 stage of that trial is now underway along with a second pivotal study (BRAVE-AA2) involving 476 participants. Both are due to generate results before the end of this year, setting up possible filings for Olumiant in AA in 2021 if positive.

Olumiant has been approved as a treatment for rheumatoid arthritis in the US since 2018, getting a first green light in the EU a year earlier, and is now approved for this indication in 65 countries worldwide.

It has failed to live up to its blockbuster potential because it was approved only at a 2 mg dose and with a black box warning on its label for risk of infections, cancer and blood clots.

Lilly has been steadily building a case for the safety of the 4 mg dose – which was more effective in arthritis trials – in the hope of raising its competitive profile against other drugs in the JAK inhibitor class, whilst also developing it for new indications such as atopic dermatitis.

Other JAK inhibitors on the market include Pfizer’s Xeljanz (tofacitinib), which also has a black box warning for infections and cancer, as well as new JAK1-selective inhibitor Rinvoq (upadacitinib) from AbbVie that is billed as having a better safety profile.

Sales of Olumiant seem to be on the rise as confidence builds with the drug – more than doubling last year to $427 million – but it still has a long way to go before it can chase down market-leader Xeljanz with a 2019 turnover of more than $2.2 billion.

Rinvoq meanwhile – which was approved towards the end of the year – brought in $47 million for AbbVie in 2019