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Friday, June 19, 2020

FDA OKs Evoke metoclopramide for diabetic gastroparesis

The FDA approves Evoke Pharma’s (EVOK +2.6%) Gimoti (metoclopramide) nasal spray for the relief of symptoms in adults with acute and recurrent diabetic gastroparesis, a disorder in which the stomach’s contractions are disrupted compromising digestion.
The company says the nod allows it to access its $5M credit line to support manufacturing and other aspects of commercialization.
The application was its second try. It received a CRL in April 2019 citing the need for additional data related to clinical pharmacology and product quality/device quality.


India triples Hydroxychloroquine capacity, lifts export ban

  • India recently lifted ban on Hydroxychloroquine exports in place since March 25
  • From 2 manufacturers, India now has 12 manufacturers for global supplies
  • Production capacity increased three times, from 100 M tablets per month to 300 M tablets per month
  • US has revoked emergency use authorisation for Hydroxychloroquine, President Donald Trump had hyped it as a ‘game changer’ in COVID-19 treatment
  • WHO dropped the drug from a multi-country clinical trial, citing ineffectiveness and potential side effects
India has lifted its ban on export of anti-malarial drug Hydroxychloroquine (HCQ) active pharmaceutical ingredients (API) and formulations, though the US drug regulator and the World Health Organisation (WHO) have now ruled against using the drug in treating COVID-19.
The move comes after an inter-ministerial High-Level Empowered Committee assessment that the number of manufacturing units of HCQ have increased from 2 to 12 and the country’s production capacity has increased three times from 100 M tablets per month to 300 M tablets per month.
This week, the US Food and Drug Administration (FDA) had revoked the emergency use authorisation (EUA) given to chloroquine phosphate and hydroxychloroquine sulfate in treating COVID-19 patients, citing lack of scientific evidence to prove its effectiveness and potential side effects. Besides, the WHO decided to stop a multi-nation Solidarity clinical trial involving HCQ.
Indian companies Zydus Cadila and IPCA Laboratories are the largest makers of Hydroxychloroquine, and India supplies over 70 percent of the global demand for this drug. The Indian drug makers had increased their capacities several times to meet the demand for COVID-19 treatment globally. As demand increased, the Directorate General of Foreign Trade (DGFT) had prohibited the export of the Hydroxychloroquine on March 25.
After Donald Trump hyped the drug as a game changer in COVID-19 treatment and asked the Indian Prime Minister to help with supplies, the demand for HCQ had soared across the globe. However, leading medical journal Lancent published an article questioning its efficacy, but later retracted its stand citing authenticity of the claims. India still uses the drug in the treatment and an Indian Council of Medical Research (ICMR) case-control study recommended using it among the healthcare workers as a prophylaxis (preventive drug).
Currently, India is having surplus of Hydroxychloroquine tablets over and above its domestic requirements. In order to treat patients in India, the Ministry of Health and Family Welfare required 122 M tablets of HCQ 200 mg tablets, and this has been procured by HLL Lifecare Limited (HLL), a central public sector undertaking entrusted with procuring essential drugs and medical devices for dealing with the pandemic. The country now has surplus capacity, as a total of 306 M tablets of HCQ 200 mg has been made available in the domestic market.
The Central Health Ministry is maintaining enough buffer stock of HCQ to cater to domestic demand. About 75 M tablets of HCQ 200 mg have been supplied to state governments, other institutions and Jan Aushadhi Kendras. Further, around 108 M tablets of HCQ 200 mg has been supplied in local pharmacies. In addition, leading manufacturers are planning to provide at least 50 M tablets in the domestic market in the month of June. The Drug Controller General of India (DCGI) conducts survey regarding availability of Hydroxychloroquine and other drugs in domestic market and a sample survey conducted on May 25-26 indicated 93.10 per cent availability of HCQ in pharmacies near to COVID-19 designated hospitals, said a government statement.
Though the ban has been lifted, domestic producers of HCQ have been mandated to supply at least 20 per cent tablets of total manufacturing for local pharmacies or trade in June.
https://www.businesstoday.in/sectors/pharma/india-triples-hydroxychloroquine-capacity-lifts-export-ban-after-us-who-find-drug-ineffective/story/407472.html

FDA grants a second approval to Ultragenyx drug for rare disease

The Food and Drug Administration on Thursday approved Ultragenyx Pharmaceutical Inc.’s RARE, 4.77% Crysvita as a treatment for some patients with tumor-induced osteomalacia (TIO), a rare disease that affects between 500 and 1,000 people in the U.S. Crysvita was first approved by the FDA in 2018 for a rare form of rickets. The drug generated net revenue of $103.7 million in 2019. “While the expansion of Crysvita’s label into TIO …is a smaller indication, which may only incrementally increase sales, it further demonstrates RARE’s ability to get programs across the finish line, providing more credibility to the mgmt. team,” SVB Leerink’s Joseph Schwartz wrote in a note to investors on Thursday. A spokesperson for Ultragenyx said the drug costs $160,000 per year for children and $200,000 per year for adults. Ultragenyx’s stock has gained 69.7% year-to-date, while the S&P 500 SPX, -0.35% is down 3.5% since the start of the year.
https://www.marketwatch.com/story/fda-grants-a-second-approval-to-ultragenyx-drug-for-rare-disease-2020-06-19

Mask Hysteria: Are We Going Too Far?

Mask recommendations are all over the place. What should we really be telling patients to do?
Kevin Campbell, MD, says evidence that everyone should wear a mask is shaky at best, and that maybe the general public shouldn’t be wasting valuable PPE resources.
The opinions expressed in this commentary are those of the author. The following transcript has been edited for clarity.
As healthcare providers, it is very clear — we must all wear masks to protect ourselves, our patients, and co-workers in the hospital setting. But what about wearing masks in other non-healthcare settings? The media will have you believe that EVERYONE should wear a mask at all times — what exactly are they basing this recommendation on? The truth is, the evidence is shaky at best.
The preponderance of evidence suggests that wearing a mask outside of a healthcare facility offers little, if any, protection from COVID-19 infection.
First of all, a COVID-19 exposure is defined as face-to-face contact within 6 feet with an infected person (symptoms or not) that is sustained for at least a few minutes — at least 10 and maybe more. There is very little chance of passing COVID-19 from a passing interaction.
According to Harvard researchers, the risk of COVID-19 transmission is strongly correlated with the duration and intensity of contact: the risk of transmission among household members can be as high as 40%, whereas the risk of transmission from less intense and less sustained encounters is well below 5%.
While a meta-analysis regarding the protective effects of wearing masks in the community has been published in the last week, the authors note that the findings on face masks and eye protection are based on very limited evidence, and none of the practices examined in the study fully protected against COVID-19 — there really is no silver bullet. Another study from Texas A&M published in the Proceedings of the National Academy of Sciences concluded that masks were essential in curbing the spread, but the study was not designed to draw these conclusions — it simply studied how viral particles were spread and extrapolated that the masks would be effective. So no real proof. There was no direct comparison or any real experiment using masks to prevent COVID-19 performed so that evidence — again — is shaky at best.
Currently, I believe that the media is using masking as a political prop and ultimately it is a reflexive reaction to anxiety and fear over the pandemic.
Many of you may be familiar with a recent piece in the NEJM that reviewed the data regarding universal masking in the COVID-19 era for hospitals — here is what the authors found and here are what I believe are the take-away messages from that study:
Masking in hospitals is already accepted practice. During COVID-19 many hospitals have begun to require both patients and providers to wear masks, and staff now wears masks in hallways and on wards, as well as in the operating and procedure rooms. In the past we weren’t allowed to wear masks in the hall.
Universal masking alone is not the answer even in the healthcare setting. A mask will not protect doctors caring for a patient with active COVID-19 if it’s not part of an overall infection-control routine including hand hygiene, eye protection, gloves, and a gown. Masks do not keep doctors and nurses from contaminating their hands and spreading the virus to patients and colleagues. If we focus too much on masks, we may in fact forget about the other important ways we can prevent transmission.
Ultimately it may be that masking does not prevent the spread of COVID-19, it actually both promotes and (in some cases) quells the spread of anxiety and fear. And furthers political agendas.
S0, what is the bottom line? To be honest, I do not think we really know conclusively at this time. However, I believe that masking for some groups in some settings is essential. But for others, it is ineffective and wastes valuable PPE resources.
According to a letter in The Lancet, “Global shortage of disposable surgical masks is a real and expanding problem. So-called mass mask panic has occurred irrespective of advice from public health authorities.”
Obviously if you are a doctor, nurse, dentist, or other healthcare worker, you must wear a mask in order to protect yourself, your patients, your family, and your colleagues.
If you are in a high-risk group — the elderly, those with diabetes, heart disease, asthma, lung disease, cancer, or if you are immunosuppressed, you should limit your social interactions and if you go out in public, you should wear a mask. These are the folks who should continue to quarantine until there is a vaccine available.
If you are going into a healthcare facility, you should wear a mask.
If you care for someone who is high risk for COVID-19, you should wear a mask.
If you are going to a public place where there is no opportunity for social distancing or if you will be in a contained space for an extended period of time, you should wear a mask.
Who does not need a mask?
If you are otherwise healthy and are not high risk, there is no evidence at this point that by wearing a mask you will decrease the chance of getting COVID-19 — simply running to the grocery store or the gas station is not a reason to wear a mask.
If you are golfing, playing tennis, exercising, riding a bike, etc. — there is no need to wear a mask.
If you are driving alone in your car, there is no need to wear a mask.
Simply put, use common sense. Do not let the media and politicians use masking as a way to fear monger and intimidate. Masking has its role, but its greatest benefits are in the healthcare setting. Random masking is a waste of resources and may limit the ability of those who really need PPE to obtain them.
We have to stop using flawed data and bad science to make decisions. Politicians are leveraging data that they do not understand in an effort to set policy and advance their own political agendas. For example, in North Carolina, Governor Roy Cooper continues to keep the state on lockdown long beyond what neighboring states have done and is now threatening to mandate masks for any citizen who goes out in public in what appears to be another gubernatorial power grab in that state.
It’s time we stopped allowing politics and fear to dictate science — science and data should dictate good politics and public policy instead.
Kevin Campbell, MD, is a cardiologist based in Raleigh, North Carolina, and chief innovation officer at biocynetic. In addition to his weekly video analyses on MedPage Today, he is the official medical expert at WNCN in Raleigh and makes frequent guest appearances on other national media outlets such as Fox News and HLN.
https://www.medpagetoday.com/infectiousdisease/covid19/87120

What Does Asymptomatic COVID-19 Look Like Under the Surface?

Asymptomatic individuals carrying SARS-CoV-2 shed the virus longer than those with COVID-19 symptoms, with other lab findings suggesting the symptomatic patients mounted more robust immune responses, a small study in China found.
Median duration of viral shedding among 37 asymptomatic patients was 19 days (interquartile range 15-26; range 6-45) versus 14 days among 37 matched symptomatic patients (IQR 9-22; log-rank P=0.028), reported Jing-Fu Qiu, PhD, of Chongqing Medical University, and colleagues, though viral shedding does not necessarily mean the patients were infectious.
Virus-specific IgG antibody titers and cytokine levels were also significantly lower among asymptomatic patients in the acute phase of infection, when viral RNA can be found in respiratory specimens, the authors wrote in Nature Medicine — both of which indicated that immune responses weren’t as strong in the asymptomatic group.
Asymptomatic transmission of COVID-19 is one of its biggest mysteries, with the World Health Organization recently reminding the public of the distinction between asymptomatic patients, who never develop symptoms, and presymptomatic patients, who go on to develop symptoms later in the course of disease.
Qiu and colleagues characterized asymptomatic carriers as the “silent spreaders” of COVID-19.
“However, our understanding of the clinical features and immune responses of asymptomatic individuals with SARS-CoV-2 infection is limited,” the researchers added.
For the study, they examined data from 178 patients with PCR-confirmed SARS-CoV-2 infection in the Wanzhou District in China, including 37 without symptoms. Median age in the latter was 41, and 22 were women. These individuals were matched by age, sex, and comorbidity with 37 symptomatic patients for antibody detection and cytokine measurement. Qiu and colleagues also included a group of 37 individuals who tested negative via RT-PCR for cytokine comparisons.
Lab values and imaging were not entirely normal for the asymptomatic group. Eleven had increased C-reactive protein levels and six had elevated levels of alanine aminotransferase. Chest CT found “focal ground-glass opacities” in 11 and “stripe shadows and/or diffuse consolidation” in another 10 of the group; in two-thirds of these 21 patients, the abnormalities were in only one lung. The remaining 16 showed entirely normal imaging.
Around 80% of both symptomatic and asymptomatic patients tested positive for IgG antibodies about 3-4 weeks after exposure. The difference was greater when examining IgM antibodies, with positive findings in 78.4% of symptomatic patients and 62.2% of asymptomatic patients.
In the early convalescent phase, defined as 8 weeks after hospital discharge, symptomatic patients had higher IgG levels, though both groups experienced over 90% decreases in IgG levels. A larger proportion of asymptomatic patients had decreases in neutralizing serum antibody levels versus symptomatic patients (81.1% vs 62.2%, respectively).
These findings should serve as a caution against assuming prior infection confers immunity to future infection, Qiu and colleagues said.
“These data might indicate the risks of using COVID-19 ‘immunity passports’ and support the prolongation of public health interventions, including social distancing, hygiene, isolation of high-risk groups, and widespread testing,” the team wrote.
Plasma levels of cytokines were also similar between asymptomatic patients and healthy controls, though significantly higher levels of stem cell factor and leukemia inhibitory factor were found in the asymptomatic group, the researchers noted, calling this a “reduced inflammatory response characterized by low circulating concentrations of cytokines and chemokines.”
Qiu and co-authors cited the varying sensitivity and specificity of antibody tests (obtained from a company called Bioscience) as a limitation to their study, adding that the results may be confounded by existing antibodies to other coronaviruses, such as SARS or MERS, as well as common cold viruses.

Disclosures
This study was supported by the National Science and Technology Major Project, the Emergency Project from the Science & Technology Commission of Chongqing, and the National Natural Science Foundation of China.
The authors disclosed no conflicts of interest.

Apple closing some U.S. stores as coronavirus spikes

Apple (NASDAQ:AAPL) will close its retail stores in Arizona, Florida, North Carolina, and South Carolina due to spiking coronavirus infection rates.
The tech giant began to reopen its U.S. stores last month. As of this week, 154 of the 271 stores were open.
Apple will close 11 of the 27 retail stores in the listed states out of “an abundance of caution.”
Source: Bloomberg.
Apple shares are down 0.5% to $349.86.
Related: During the fiscal Q2 earnings call in April, CEO Tim Cook said the last three weeks of the quarter felt the pressure of the retail store closures outside of China.
https://seekingalpha.com/news/3584631-apple-closing-u-s-stores-coronavirus-spikes

BofA Raises Jazz Pharma Estimates After Zepzelca Update

Jazz Pharmaceuticals PLC JAZZ 0.5% provided encouraging updates on its commercial efforts in a recent conference call on the lung cancer drug Zepzelca, according to BofA Securities.

The Jazz Pharma Analyst

Jason Gerberry maintained a Buy rating on Jazz Pharmaceuticals and raised the price target from $165 to $167.

The Jazz Pharma Thesis

Zepzelca received accelerated FDA approval for the treatment of metastatic small cell lung cancer.
Gerberry named three takeaways from the conference call:
  • Launch readiness: Jazz Pharma expects to commercially launch Zepzelca by early July. The company submitted data to the National Comprehensive Cancer Network for preapproval and expects price compendium listing by late June or early July, the analyst said.
  • Prescriber focus: Jazz Pharma will initially focus on commercialization among the top 1,500 prescribers versus a total of 6,000. The company already has group purchasing organization contracts in place, with the government and commercial book of business representing 64% and 32%, respectively.
  • Confirmatory approval: While originally not planned as confirmatory, the FDA has indicated that ATLANTIS can be used for confirmatory purposes.
  • “JAZZ does not consider confirmatory approval as a gating factor for uptake of Zepzelca, given high unmet need,” Gerberry said.
BofA Securities raised its estimate for Zepzelca peak year sales from $500 million to $593 million to reflect higher penetration.
https://www.benzinga.com/analyst-ratings/analyst-color/20/06/16301309/bofa-raises-jazz-pharma-estimates-after-zepzelca-update