Lexicon gets OK for heart failure med partnership

 Shares of Lexicon Pharmaceuticals, Inc. (LXRX) said it received a regulatory feedback that clears a key hurdle for partnership discussions around sotagliflozin in heart failure.

Lexicon Pharmaceuticals said it received U.S. Food and Drug Administration regulatory feedback that the results of its SOLOIST and SCORED Phase 3 clinical studies can support a new drug application submission for an indication to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent visits for heart failure in adult patients with type 2 diabetes with either worsening heart failure or additional risk factors for heart failure.

https://www.nasdaq.com/articles/stock-alert%3A-lexicon-pharmaceuticals-surges-35-2021-01-14

Organogenesis Enrolls for Phase 3 Trial of Knee Osteoarthritis Treatment

 Organogenesis Holdings Inc. (Nasdaq: ORGO), a leading regenerative medicine company focused on the development, manufacture and commercialization of product solutions for the Advanced Wound Care and Surgical & Sports Medicine markets, today announced that the first patient has been enrolled in its pivotal Phase 3 clinical trial evaluating the safety and efficacy of ReNu®, a cryopreserved amniotic suspension allograft (ASA), for the management of symptoms associated with knee osteoarthritis (OA).

“We are very pleased to have initiated our ReNu pivotal Phase 3 trial,” said Patrick Bilbo, Chief Operating Officer for Organogenesis. “This significant milestone comes on the heels of the FDA’s RMAT designation underscoring the strength of our existing ReNu clinical evidence and its potential to address a largely unmet medical need. We look forward to leveraging our RMAT designation to work closely with the FDA to expedite the review of ReNu as the study progresses.”

The Phase 3 study is a prospective, double-blind, multicenter, placebo-controlled, parallel group, randomized control trial (RCT) of ReNu in 474 subjects with moderate to severe symptomatic knee osteoarthritis. Patients will be randomized to either a single intra-articular (IA) injection of saline (placebo control) or a single injection of ReNu. The primary efficacy endpoint is the difference in pain from baseline to 6 months as assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).

OA is a degenerative joint disease that affects more than 30 million Americans and accounts for more than $185 billion in annual expenditures. Knee OA has been estimated to affect approximately 14 million Americans ages 25 and older, with nearly 8 million under the age of 65. The number of knee replacement surgeries is growing every year, and expected to rise from approximately 680,000 Americans in 2014 to 1.28 million Americans in 2030.

https://www.globenewswire.com/news-release/2021/01/14/2158521/0/en/Organogenesis-Enrolls-First-Patient-in-Pivotal-Phase-3-Clinical-Trial-of-RMAT-Designated-ReNu-for-Knee-Osteoarthritis.html

Catalent tackles Warp Speed juggling act with new $50M Bloomington line, Acorda plant buyout

 Catalent hustled to expand its manufacturing capacity last year as it juggled a surge of COVID-19 work with its regular production orders. That pandemic agenda caused problems in December, when the CDMO had to divert manufacturing slots for Horizon's drug Tepezza to crank out Warp Speed vaccines. 

The laser focus on vaccines won't abate any time soon, CEO John Chiminski said Monday at this year's annual J.P. Morgan healthcare conference—but a new production line is now on the way, and, as of Wednesday, it has a fresh buyout on the docket.

Last month, Horizon said its thyroid eye disease med Tepezza would run scarce from the end of December into 2021, thanks to COVID-19 shot orders dominating the agenda at Catalent's Bloomington, Indiana, facility. Operation Warp Speed had leveraged the Defense Production Act of 1950, forcing Catalent to cancel some Tepezza manufacturing slots, Horizon said. The company said it planned to increase the size of each lot of the drug Catalent produces. It's also working to sign a second contract manufacturer.

Chiminski this week shed some light on that situation—and floated a potential timeline for when customers could expect the capacity jam to ease. 

“We’re in a certain situation in Bloomington where we do have products there that are given government-rated orders—so, they’re given priority as part of the Defense Production Act and so forth,” he said.

The problem isn't affecting Horizon alone. "It has been a challenge for more than one customer as we juggle allocating that capacity for the rated orders versus the work that we have there," Chiminski said. 

To compensate, Catalent has plowed $50 million into a new line at its Bloomington site, where it's working on vaccines from Moderna and Johnson & Johnson. That line is expected to come online in April. For the "three- to four-month period" until then, Catalent will have to juggle capacity for Warp Speed orders with the work it owes its regular customers, Chiminski said. 

The "other problem," as the CEO put it, is Catalent's Madison, Wisconsin, facility—also subject to orders from Warp Speed. “That one will be a little bit more challenging, and we’ll probably have to work a little bit, hopefully, with OWS and our customers to kind of manage that in the interim," Chiminski said. 

Meanwhile, the company isn't letting its COVID-19 work disrupt expansions into other areas. For one, the company expects to lay out "well over" half a billion dollars in new investment in 2021, largely weighted toward biologics build-outs, Chiminski said. “A notable portion" of that investment includes expansions it had already planned, he said, but will now accelerate " to meet the elevated demand environment we’re seeing now in our biologics and cell and gene therapy offerings—in part driven by the demand related to COVID-19.”

It's also pursuing new technologies like plasmid DNA, next-generation cell therapy, nucleic acid-based therapeutics and more, Chiminski said. 

As if to illustrate its post-pandemic ambitions, Catalent on Wednesday agreed to pony up $80 million to buy Acorda Therapeutics' manufacturing and packaging operations in Massachusetts. The deal, expected to close in the first quarter of 2021, will see Catalent take charge of a 90,000-square-foot Acorda facility to expand spray-dried dispersion and dry powder encapsulation and packaging.

The Chelsea, Massachusetts site will complement Catalent's 180,000 square-foot inhalation development facility in Morrisville, North Carolina, which develops and manufactures metered-dose inhalers, nasal sprays and dry powder inhalers, the company said. 

https://www.fiercepharma.com/manufacturing/cdmo-catalent-tackles-warp-speed-juggling-act-new-50m-bloomington-line-acorda

Medtronic in First-of-Kind Adaptive Deep Brain Stimulation (aDBS) Trial in Parkinson's

 Medtronic plc (NYSE:MDT), the global leader in medical technology, today announced the first enrollment in ADAPT-PD (Adaptive DBS Algorithm for Personalized Therapy in Parkinson's Disease), its trial evaluating the safety and efficacy of adaptive deep brain stimulation (aDBS) in patients with Parkinson's Disease (PD). Adaptive deep brain stimulation is an investigational feature of the Percept™ PC device that could be enabled if approved. The investigational feature used in this study allows for automated adjustment of brain stimulation to provide therapy to manage symptoms of Parkinson's disease based on a patient's clinical state.

The randomized study will take place across 12 study sites at leading Movement Disorders research centers in the United States, Europe, and Canada. An estimated 36 subjects will undergo a total evaluation period of 15 months. The primary endpoint of ADAPT-PD will compare standard continuous DBS (cDBS) to aDBS for hours of 'On' time without troublesome dyskinesias, a measure of treatment efficacy versus side effects, as reported by patient diary. Qualifying subjects in the study will receive cDBS at baseline followed by randomized evaluation of two different aDBS algorithms in a blinded manner.

Dr. Helen Bronte-Stewart, the John E. Cahill Family Professor in the Department of Neurology and Neurological Sciences at Stanford University and who is the North American principal investigator for the ADAPT-PD study, enrolled the first patient at the Stanford Movement Disorders Center. Dr. Bronte-Stewart and her collaborators previously laid the foundation for ADAPT-PD by performing the first closed loop deep brain stimulation studies in Parkinson's disease using an investigational prototype research-only system (Activa™ PC+S-Nexus D3). ADAPT-PD represents an evolutionary leap from these early studies in that sensing of brain signals and automated adjustment of stimulation are performed by using unlocked investigational features of the commercially available Percept PC DBS device, allowing patients in the study to be both treated and measured while outside the clinic.

According to the Parkinson's Foundation, more than 10 million people worldwide are living with Parkinson's disease and while similar, the progression of symptoms is often different from one patient to another due to the diversity of the disease. People with PD may experience tremor; slowness of movements (bradykinesia); limb rigidity; gait and balance challenges.

DBS is a well-established, safe and effective therapy for the treatment of motor symptoms in PD, including tremor (shaking); slowed movement (bradykinesia); and stiffness (rigidity) when medications aren't as effective as they used to be. Opportunities exist to improve the efficacy of DBS therapy. Current commercially-approved DBS systems deliver stimulation continuously (cDBS) and are adjusted manually within physician-defined limits to optimize therapy for the patient. In contrast, aDBS therapy may individualize and optimize PD therapy for the same motor symptoms as with cDBS by automatically adjusting stimulation within physician-defined limits, based on brain signals detected by the DBS system. ADAPT-PD will be using the Percept PC DBS system with investigational aDBS feature. While the aDBS feature is investigational and has not been approved for commercial use, the Percept PC device (cDBS) was approved by the FDA in June 2020. The Percept PC device (cDBS) utilizes proprietary BrainSense™ technology making it the only DBS system with the ability to capture patient-specific brain signals. The sensing feature of the Percept PC system is intended for use in patients receiving DBS where chronically-recorded bioelectric data may provide useful, objective information regarding patient clinical status. Clinical benefits of brain sensing have not been established.

https://www.biospace.com/article/releases/medtronic-launches-first-of-its-kind-adaptive-deep-brain-stimulation-adbs-trial-in-parkinson-s-disease-patients/

Mapping the Future of the COVID-19 Pandemic

 A drop-off in virulence is possible for the SARS-CoV-2 virus -- once enough of the global population has been vaccinated or exposed to it, according to a new study from scientists at Emory University and The Pennsylvania State University.

The findings, published Tuesday in Science, use immunological and epidemiological data on endemic, cold-causing human coronaviruses to model transmission in a world where most adults have had an initial immune exposure to the virus, via infection or vaccine.

The authors predict that SARS-CoV-2 – unlike more deadly coronavirus cousins SARS and MERS – may eventually spread like the most common, non-deadly human coronaviruses do, providing initial exposure to children under the age of 5, when immune responses are less likely to result in serious illness.

According to the model, a virus’s infection fatality ratio is mostly dependent on how severe childhood infections are, and a coronavirus that with the morality of MERS infections but with the endemic pattern of COVID-19 could only by curbed with mass childhood vaccinations.

The model is based on four existing endemic human coronaviruses. Previous studies have shown that reinfection throughout adulthood after a childhood infection is commonplace, and may even continuously improve human immune response to the strains. As a result, the authors warn that the apparent low rates of reinfection with COVID-19 recently observed could actually dampen this drift toward lower virulence.

Although the paper does not offer a timeline for the transition from COVID-19 pandemic to a safer endemic, it does suggest that mass vaccinations could be halted at the end of this transient period, depending on the immunological response to vaccines.

If the response to vaccines mimics the response to common cold-type human coronavirus infections – specifically, primary introduction to the virus in early childhood and short periods of protection against reinfection, followed by long-lived protection against severe disease – COVID-19 could more quickly become endemic, according to the study.

Other experts have cautioned that this model is only one possible scenario. Jennifer Gommerman, a professor of immunology at the University of Toronto, told the New York Times  that introducing a vaccine via intravenous injection meant the body is not introduced to natural pathogens in the upper respiratory tract like usual, so it is remains unclear whether the immune reaction would be consistent enough for the model to hold. And the lack of data for endemic human coronaviruses in naïve older people means comparisons might be premature, said Marc Lipsitch, a professor of epidemiology at Harvard University’s Harvard T.H. Chan School of Public Health.

https://www.biospace.com/article/mapping-the-future-of-the-covid-19-pandemic/

Russia to submit Sputnik V vaccine for EU approval

  Russia will submit a formal application to the European Union next month for approval of its Sputnik V coronavirus vaccine, the head of Russia’s sovereign wealth fund said on Thursday.

Peer-reviewed results of the vaccine would be released shortly and would demonstrate its high efficacy, fund chief Kirill Dmitriev said in an interview at the Reuters Next conference.

He said Sputnik V would be produced in seven countries. He added that regulators in nine countries are expected to approve the vaccine for domestic use this month. It has already been approved in Argentina, Belarus, Serbia and elsewhere.

Russia, which has the world’s fourth-highest number of COVID-19 cases, plans to begin mass vaccinations next week.

https://www.reuters.com/article/us-health-coronavirus-russia-dmitriev/russia-to-submit-sputnik-v-vaccine-for-eu-approval-says-rdif-chief-idUSKBN29J1DX

Two members of WHO delegation to Wuhan held back over health screening

 Two members of a World Health Organization-led team that arrived on Thursday in China’s Wuhan city to investigate the origins of COVID-19 remained behind in Singapore after testing positive for coronavirus antibodies, the global body said.

The team of 15 had all tested negative for the disease prior to leaving their home countries, and underwent further testing while in transit in Singapore.

The results of nucleic acid tests were negative but showed two of the members had coronavirus antibodies, the Geneva-based agency said in a tweet.

“They are being retested for both IgM and IgG antibodies,” the WHO said.

It is the latest setback for a mission beset by delay as well as concern over how much access the team will get.

The rest of the team arrived in Wuhan from Singapore late on Thursday morning on a budget airline and they were expected to head into two weeks of quarantine.

“Relevant epidemic prevention and control requirements and regulations will be strictly enforced,” Chinese foreign ministry spokesman Zhao Lijian told a regular briefing on Thursday in response to a question about the two team members.

The team tasked with investigating the origins of the novel coronavirus that sparked the global pandemic had been set to arrive earlier this month. China’s delay of their visit drew rare public criticism from the head of the WHO.

The group left the airport terminal in Wuhan through a plastic quarantine tunnel marked “epidemic prevention passage” for international arrivals and boarded a cordoned-off bus that was guarded by half a dozen security staff in full protective gear. The coronavirus was initially linked to a seafood market in the central city of Wuhan.

Team members did not speak to reporters, although some waved and took pictures of the media from the bus as it departed.

The United States, which has accused China of hiding the extent of its initial outbreak a year ago, has called for a “transparent” WHO-led investigation and criticised the terms of the visit, under which Chinese experts have done the first phase of research.

LOCAL OUTBREAKS

The team arrived in China as the country battles a resurgence of coronavirus cases in its northeast after managing to nearly stamp out domestic infections in recent months.

Peter Ben Embarek, the WHO’s top expert on animal diseases that cross to other species, who went to China on a preliminary mission last July, was leading the team going to Wuhan, a WHO spokesman said previously.

Hung Nguyen, a Vietnamese biologist who was part of the team, told Reuters during a stopover in Singapore on Wednesday that he did not expect any restrictions on the group’s work in China, but cautioned the team might not find clear answers.

After completing quarantine, the team will spend two weeks interviewing people from research institutes, hospitals and the seafood market in Wuhan where the new pathogen is believed to have emerged, Hung added.

The group would mainly stay in Wuhan, he said.

Last week, WHO director-general Tedros Adhanom Ghebreyesus said he was “very disappointed” that China had still not authorised the team’s entry for the long-awaited mission, but on Monday, he welcomed its announcement of their planned arrival.

“What we would like to do with the international team and counterparts in China is to go back in the Wuhan environment, re-interview in-depth the initial cases, try to find other cases that were not detected at that time and try to see if we can push back the history of the first cases,” Ben Embarek said in November.

China has been pushing a narrative via state media that the virus existed abroad before it was discovered in Wuhan, citing the presence of the virus on imported frozen food packaging and scientific papers claiming it had been circulating in Europe in 2019.

“We are looking for the answers here that may save us in future - not culprits and not people to blame,” the WHO’s top emergency expert, Mike Ryan, told reporters this week, adding that the WHO was willing to go “anywhere and everywhere” to find out how the virus emerged.

Other team member Marion Koopmans, a virologist at Erasmus University Medical Center in the Netherlands, said last month it was too soon to say whether the SARS-CoV-2 virus had jumped directly from bats to humans or had an intermediate animal host.

“At this stage what I think we need is a very open mind when trying to step back into the events that led eventually to this pandemic,” she told reporters.

https://www.reuters.com/article/us-health-coronavirus-who-china/two-members-of-who-delegation-to-wuhan-held-back-over-health-screening-idUSKBN29J05P