Adamas Pharma bails on amantadine in MS patients with walking impairment

Citing “limited” commercial opportunity and the need to conduct another late-stage clinical trial, Adamas Pharmaceuticals (NASDAQ:ADMS) has decided to terminate development of ADS-5102 (amantadine) extended-release capsules for the treatment multiple sclerosis (MS) patients with walking impairment.

The company made the decision after a comprehensive analysis of results from the Phase 3 INROADS study that, it says, validated topline results reported in December 2019 and informed a revised target product profile reflecting the scale of clinical benefit observed in the trial. Additional research projected unattractive commercial prospects, however. Further engagement with the FDA confirmed the need for a new Phase 3 study.

The company markets amantadine extended-release capsules under the brand name Gocovri, approved in the U.S. in August 2017 for the treatment of dyskinesia in Parkinson’s disease (PD) patients. Its supplemental application seeking approval to treat OFF episodes in PD patients is currently under FDA review with an action date of February 1, 2021.

https://seekingalpha.com/news/3583962-adamas-pharma-bails-on-amantadine-in-ms-patients-walking-impairment

Repare Therapeutics files for upsized IPO

Repare Therapeutics (RPTX) has filed a preliminary prospectus for its IPO of 10M common shares at $18 – 20 per share.

Two days ago, it filed the same for an initial public offering of ~7.4M shares at $16 – 18.

The Cambridge, MA-based biotech develops precision oncology treatments based on synthetic lethality (SL), an approach to drug development focused on genomic instability, including DNA damage repair. SL pertains to a deficiency in either of two genes that is tolerated in cells, but leads to cell death when both genes are present. The company employs its proprietary, genome-wide, CRISPR-enabled SNIPRx platform to identify and develop highly targeted therapeutics for tumors that contain a mutation in one gene of an SL pair, making them prime candidates for intervention by targeting the other gene in the pair.

SL-related tickers: IDEAYA Biosciences (NASDAQ:IDYA), GlaxoSmithKline (NYSE:GSK)

https://seekingalpha.com/news/3583977-repare-therapeutics-files-for-upsized-ipo

Researchers Overdosing Covid Patients on Hydroxychloroquine – AAPS Suit

Until President Trump suggested that hydroxychloroquine (HCQ, Plaquenil™) might help COVID-19 patients, it was generally considered a very safe drug, observes the Association of American Physicians & Surgeons (AAPS). It was approved by the FDA in 1955 and has been used by hundreds of millions of patients worldwide for malaria, lupus, and rheumatoid arthritis. Physicians do not generally require an electrocardiogram before prescribing it. Apparently because of alarming media coverage, many patients are now expressing fear that HCQ is dangerous because of cardiac effects, states AAPS. Outgoing AMA president Patrice Harris, M.D., told the media that “you could lose your life.” Widely reported studies have been stopped because of lack of benefit in seriously ill hospitalized COVID-19 patients and the occurrence of cardiac rhythm disturbances. AAPS notes the following: Late in the disease, antivirals are unlikely to help because patients are dying of organ damage and blood clots, possibly due to immune overreaction. The SARS-CoV-2 virus may infect the heart, and this may cause arrhythmias. Doses of HCQ in some trials, such as the UK’s “Recovery” trial and the multinational World Health Organization (WHO) Solidarity trial may be toxic or even lethal, and much higher than recommended for any medical condition. The cumulative dose of this long-acting drug in the “Recovery” trial (9.6 grams) is four times as high as used in India. A Brazilian study published in JAMA is being investigated by Brazilian governmental authorities for ethical reasons: investigators were giving seriously ill patients a lethal dose of chloroquine. HCQ (hydroxychloroquine) is much safer than chloroquine but like all drugs is toxic in too-high doses. Americans are being urged to “follow the science.” But AAPS asks: “How can we trust the established authorities or prestigious journals when, in this perilous time, trials of an available, inexpensive, long-established drug appear to be designed to fail, while risking the lives of their subjects through deliberate or negligent drug overdoses?” The Association of American Physicians and Surgeons (AAPS) has represented physicians of all specialties in all states since 1943. The AAPS motto is omnia pro aegroto, meaning everything for the patient. View original content to download multimedia:http://www.prnewswire.com/news-releases/researchers-overdosing-covid-19-patients-on-hydroxychloroquine-states-association-of-american-physicians–surgeons-aaps-301078986.html SOURCE Association of American Physicians and Surgeons (AAPS) https://www.biospace.com/article/releases/researchers-overdosing-covid-19-patients-on-hydroxychloroquine-states-association-of-american-physicians-and-amp-surgeons-aaps-/

Big pharma’s late-stage pipeline smallest in a decade

There are few places where evidence of the Covid-19 new world order is more apparent than biopharma M&A. Smaller transactions are getting away – Novo Nordisk’s acquisition of Corvidia for example – however deal volumes look set to nose dive this year.
The pandemic could have come at a particularly bad time for big pharma. An Evaluate Vantage analysis shows that the number of novel, late-stage assets sitting in the pipelines of the world’s biggest drug makers is at a low for the decade, having been in decline for the last four years.
Those hoping to do some form of portfolio building will struggle to follow through on these plans as restrictions on global travel continue to be in place.
When it comes to novel projects, not only have the numbers fallen from acquisitions and in-licensing, there has also not been any compensatory uplift from organic development.
This analysis was conducted using historical pipeline data from EvaluatePharma, with a count conducted in April of every year. This should collect every project that enters phase III – a phase transition in under 12 months is very unlikely – and encompasses the 11 global pharmaceutical majors.

In April 2016 there were 82 novel projects sitting in these pipelines, a figure that dropped to 49 the same month this year. One explanation is the streamlining of portfolios that has happened at several companies under new management – Glaxosmithkline and Sanofi, for example.
A focus on oncology at many groups could be another reason, with research teams increasingly focusing on brand extensions rather than new approvals: think of the huge number of indications that Keytruda is sold in.
Notably, this declining trend is not seen in the pipelines managed by other big drug makers. For any company whose market cap averaged at $30bn over the period, including those that have been acquired over the period, rates seem fairly steady over the decade in question, suggesting that the late-stage shrinkage is a big pharma phenomenon. This raises the question of whether the analysis reflects a deliberate focusing of resources, or the fact that assets are becoming harder to acquire.

Easy access to financing is allowing younger developers to hold on to their assets – and pushing valuations up. A look at transactions announced so far this year shows that 2020 had already started slowly – throw in the pandemic, and the outlook for deal-making this year is pretty dire.
Stephanie Léouzon, partner and head of Torreya Europe, a global investment bank, believes that earlier-stage deals will be favoured over later-stage transactions this year: “These type of deals are easier to complete, if you have to do M&A,” she says. “What we are also seeing is where M&A is declining, partnering and licensing across the industry continues to be very active.”
Evan Lippman, Takeda’s head of corporate development, M&A and valuation believes that quick fixes in the form of mega mergers are off the table for now due to current market uncertainty.
Any large acquisitions that do happen might also look different. “Companies are very mindful of their capital structures right now, so we might see more structured deals rather than outright M&A, with more use of contingent value rights,” he says.
Still, few believe that old fashioned deal making is over. “While there might be a short-term impact in terms of M&A from Covid you have to remember most companies are making long-term bets,” says Andy Pasternak, chief business officer at Horizon Therapeutics.
Perhaps these longer-term bets will boost the size of late-stage pipelines in a few years time. But if the deal trends below are anything to go by, big pharma’s phase III portfolio is set to stay relatively small for a while.

https://www.evaluate.com/vantage/articles/data-insights/ma/big-pharma-sports-smallest-late-stage-pipeline-decade

Russia says it already uses dexamethasone to treat coronavirus

Russia already uses dexamethasone to treat patients with the novel coronavirus, but does not view it as a panacea against COVID-19, the RIA news agency cited Russian health ministry official Sergei Avdeev as saying on Wednesday.
Dexamethasone, a cheap and widely used steroid, has become the first drug shown to be able to save the lives of critically ill COVID-19 patients in what scientists said is a major breakthrough in the coronavirus pandemic.
https://www.reuters.com/article/us-health-coronavirus-steroid-russia/russia-says-it-already-uses-dexamethasone-to-treat-coronavirus-patients-ria-idUSKBN23O1PS

Gilead to enroll pediatric patients for late-stage remdesivir study

Drugmaker Gilead Sciences said on Wednesday it will soon begin enrollment of pediatric patients with moderate-to-severe COVID-19 in a late-stage study testing its experimental drug, remdesivir.
The trial will assess the effectiveness and safety of the drug in the patients, which would include newborns to adolescents, across more than 30 sites in the United States and Europe, the company said.
Gilead’s remdesivir, which has been at the forefront in the fight against the virus and has been given emergency use authorization in some countries, could be helpful in some patients after data showed it could shorten the time taken to recover from the disease.
The company is already running a late-stage study testing the drug in 6,000 patients with severe COVID-19.
https://www.reuters.com/article/us-health-coronavirus-gilead-sciences-st/gilead-to-enroll-pediatric-patients-for-late-stage-remdesivir-study-idUSKBN23O3EJ

Steroid should be kept for serious coronavirus cases, WHO says

A cheap steroid that can help save the lives of patients with severe COVID-19 should be reserved for serious cases in which it has been shown to provide benefits, the World Health Organization said on Wednesday.

WHO chief Tedros Adhanom Ghebreyesus said research was at last providing “green shoots of hope” in treating the virus, which has killed more than 400,000 people worldwide and infected more than 8 million.
Trial results announced on Tuesday by researchers in Britain showed dexamethasone, a generic drug used since the 1960s to reduce inflammation in diseases such as arthritis, cut death rates by around a third among the most severely ill coronavirus patients admitted to hospital.
That makes it the first drug proved to save lives in fighting the disease. Countries are rushing to ensure that they have enough of it on hand, although medical officials say there is no shortage.
Some doctors were cautious, citing possible side-effects and asking to see more data.
A patient in Denmark received dexamethasone on Wednesday, local news agency Ritzau reported. The doctor who prescribed the drug said the medical profession was well acquainted with its side-effects.
The head of the WHO’s emergencies programme, Mike Ryan, said the drug should only be used in those serious cases where it has been shown to help.

“It is exceptionally important in this case, that the drug is reserved for use in severely ill and critical patients who can benefit from this drug clearly,” he told a briefing.
Britain has increased the amount of dexamethasone it has in stock and on order to 240,000 doses, Health Minister Matt Hancock said.
Methylprednisolone, a steroid similar to but less potent than dexamethasone, has been used in Sweden since March, a Stockholm-based doctor told media.
The steroid was introduced to standard practice after it proved effective on a coronavirus patient who wasn’t showing signs of recovery with other treatments, Lars Falk, of the New Karolinska Hospital, told Sweden’s Dagens Nyheter.
The dexamethasone study’s results are preliminary, but the researchers behind the trial said it suggests the drug should become standard care in severely stricken patients.

‘NO SILVER BULLET’

For patients on ventilators, the treatment was shown to reduce mortality by about a third, and for patients requiring only oxygen, deaths were cut by about one fifth, according to preliminary findings shared with the WHO.

“This is the first treatment to be shown to reduce mortality in patients with COVID-19 requiring oxygen or ventilator support,” Tedros said in a statement late on Tuesday.
“WHO will coordinate a meta-analysis to increase our overall understanding of this intervention. WHO clinical guidance will be updated to reflect how and when the drug should be used in COVID-19,” the agency added.
South Korea’s top health official expressed caution about dexamethasone and the European Union and Switzerland both said they were awaiting more information.
An Italian expert said that dexamethasone was no silver bullet.
“The study showed a marginal reduction in deaths,” said Lorenzo Dagna, immunology head at IRCCS San Raffaele Scientific Institute in Milan. “We’re light years away from being able to say we’ve found the cure against COVID.”
On the positive side, he added, the drug is cheap and plentiful.
As the new coronavirus has wreaked havoc on global economies, some countries have moved quickly to authorise emergency use of medicines only to later backtrack.
The U.S. Food and Drug Administration, for instance, withdrew emergency authorisation for hydroxychloroquine, a malaria drug touted by U.S. President Donald Trump and others against COVID-19, after studies showed it did not help.
The WHO said on Wednesday that testing of hydroxychloroquine in its large multi-country trial of treatments for COVID-19 patients had been halted after research showed no benefit.
“We have been burned before,” Dr. Kathryn Hibbert, director of the medical intensive care unit at Harvard’s Massachusetts General Hospital, said, expressing caution about dexamethasone.
https://www.reuters.com/article/us-health-coronavirus-steroid-who/steroid-should-be-kept-for-serious-coronavirus-cases-who-says-idUSKBN23O0LU