Pfizer bets on biotech flu vaccine in $425 million BioNTech alliance

 Pfizer has agreed to pay German biotech firm BioNTech up to $425 million (£334.33 million) in an alliance to develop more effective influenza jabs, the latest among several major pharma companies to bank on a promising new genetic approach.

FRANKFURT (Reuters) – Pfizer has agreed to pay German biotech firm BioNTech up to $425 million (£334.33 million) in an alliance to develop more effective influenza jabs, the latest among several major pharma companies to bank on a promising new genetic approach.

Privately-held BioNTech will receive $120 million upfront plus up to $305 million depending on certain development achievements as well as tiered royalties on futures sales in the double-digit percentage range, the two companies said in a statement on Thursday.

Mainz-based BioNTech, valued at $2.3 billion in a January financing round, is specialising in so-called messenger RNA (mRNA) molecules that instruct human cells to produce therapeutic proteins or to launch an immune response.

The emergent field has seen drugmakers such as AstraZeneca, Eli Lilly and Sanofi partner up with biotech firms.

“mRNA vaccines offer a novel approach to code for any protein or multiple proteins, and the potential to manufacture higher potency flu vaccines more rapidly and at a lower cost than contemporary flu vaccines,” said Kathrin Jansen, the head of Pfizer’s vaccine research and development unit.

Flu jabs are currently produced from chicken eggs based on the previous flu season’s viral strains. The alliance partners hope to offer a vaccine that can be quickly adjusted to the latest viral mutations, which can also be a major advantage in case of a pandemic threat from avian flu.

Pfizer will take over testing on humans and commercialisation of BioNTech’s flu vaccines once the German firm, which is Europe’s largest unlisted biotech firm by staff numbers, has completed the first clinical study.

Having raised $270 million from investors early this year, BioNTech is also developing personalised immunotherapies for cancer and is eyeing a future public listing.

The company competes in the race for mRNA therapies with groups such as Massachusetts-based Moderna Therapeutics, Belgium’s eTheRNA and domestic rival CureVac.

CureVac’s work on jabs to prevent malaria and influenza won more financial backing from its investor the Bill & Melinda Gates Foundation in a February agreement.

BioNTech, for its part, has previously attracted alliance partners including Roche’s Genentech, Eli Lilly, Sanofi, Genmab and Bayer Animal Health.

As part of the upfront payment, Pfizer will acquire a “smaller” stake in the Germany company. Precise terms were not disclosed.

Biotech investors Thomas and Andreas Struengmann, who sold their generic drugs business Hexal to Novartis in 2005, will remain majority shareholders in BioNTech.

https://bit.ly/2OI8REr

Individuals shot by police show patterns of recent prior hospitalizations, arrests

A study published in the American Journal of Preventive Medicine found that more than 50 percent of people with assault-related or legal intervention (LI) firearm injuries due to law enforcement actions and over 25 percent of individuals with self-inflicted or unintentional firearm injuries were arrested, hospitalized, or both in the two years prior to being shot. While LI firearm injuries are comparatively rare, they are on the rise, increasing 10 percent nationally in the United States over the last decade. The study’s findings contribute important evidence that can be used to reduce and prevent these injuries and deaths.

“Looking at arrest and hospital records in Seattle, we identified some patterns among intent-specific firearm injuries. Notably, individuals shot by police had arrest histories similar to those shot in assaults and homicides and medical histories similar to those with self-inflicted firearm injuries. The individuals who are injured in LI encounters also exhibit disruptive, impulsive, and conduct-related disorders more frequently than individuals in our control group and increased risk of interpersonal and self-directed violence,” explained Brianna M. Mills, Ph.D., Harborview Injury Prevention and Research Center (HMC), University of Washington, Seattle, WA, USA. “Our results show how many firearm injuries occur after a series of encounters with institutions that are meant to help individuals in crisis, but unfortunately have failed to deter the situation leading to the injury. We believe that each of these encounters represents an opportunity for more effective interventions and long-term solutions.”

The case-control study conducted by Dr. Mills and colleagues identified 763 individuals who sustained firearm injuries and 335 who had motor vehicle passenger injuries in Seattle over a five-year period (2010-2014). Data were obtained from from the HMC trauma registry and Washington State death records. Diagnoses from prior hospitalizations were extracted from the Comprehensive Hospital Abstract Reporting System (CHARS) maintained by the Washington State Department of Health, which documents inpatient treatment and observation stays in all state-licensed acute care, long-term, and cancer specialty hospitals in Washington, including psychiatric units. Arrest data came from the Washington State Identification System criminal history database.

Patients were grouped by firearm injury cause: assault-related (58.1 percent), self-inflicted (28.6 percent), unintentional (9.3 percent), and legal intervention (4.1 percent). In the control group were motor vehicle passenger accidents. The records for the two years prior to the incidents were mined for information about misdemeanor and felony arrests, as well as diagnoses of substance abuse (alcohol, marijuana, and other drugs), and mental disorders (psychosis, depression/anxiety, and impulsivity/conduct disorder). By comparing arrest history, substance use, and mental disorders within the same geographic region and time period in a single investigation, the study helped to clarify how each contributes to the risk of sustaining intent-specific firearm injuries. It is important to note that the findings should be interpreted as providing information on non-causal markers of increased risk, rather than causal risk factors.

Key findings:

In the two years prior to being shot, individuals with fatal and non-fatal LI firearm injuries were:

• 22 times more likely to have an impulsivity/conduct disorder diagnosis than passengers injured in a motor vehicle collision
• 11 times more likely to have been diagnosed with a substance use disorder than passengers injured in a motor vehicle collision
• 7 times more likely to have a prior felony arrest, depression/anxiety diagnosis, or psychosis diagnosis than passengers injured in a motor vehicle collision

While there is increasing public awareness of the scope and burden of firearm injury in the US, police shootings, in particular, have received relatively less attention in research over the past decades than other types of firearm injuries. Because they are occurring with increasing frequency, with profound negative implications for individuals, their families, and communities where they occur, this study is an important step for building − and using − an evidence base to understand the connections and distinctions between different types of firearm injuries.

These findings highlight a potential role for medical and law enforcement professionals in preventing LI injuries as they encounter vulnerable individuals. Screening instruments for mental disorders or risk of firearm violence can be validated and potentially adapted for use in multiple settings. Tools to identify and utilize intervention opportunities during medical or legal encounters may help prevent later law enforcement confrontations. Coordination between police and mental health services, including de-escalation training for officers tasked as first responders and specialized crisis response teams with decision-making authority given to qualified mental health professionals, may lead to better avoidance of confrontations between police and individuals in crisis. Police departments, including Seattle’s, have begun to make some of these changes with good results.

“Moving the conversation forward requires understanding the connections and distinctions between different types of firearm injuries so we can create focused and effective interventions,” commented Dr. Mills. “We invite other researchers to collaborate with us to replicate the study in other cities and determine if some of the patterns we uncovered are generalizable or specific to Seattle.”

 Explore further: Pediatric hospitalization for gun injuries higher in urban areas

More information: “Prior Arrest, Substance Use, Mental Disorder, and Intent-Specific Firearm Injury,” American Journal of Preventive Medicine (2018). DOI: 10.1016/j.amepre.2018.04.041

https://bit.ly/2KT4Mec

Given a Death Sentence, ALS Patients Wait for Potential Disease Cure

On Aug. 5, 2014, Scott Hayes of Wilson, N.C. received some of the worst news imaginable. He was diagnosed with amyotrophic lateral sclerosis (ALS). He was given three to five years to live by his doctors.

Hayes had been a vigorous and hearty man, but the disease wore his body down. His legs were no longer able to support him and he was soon confined to a wheelchair. His body continued to deteriorate and he lost the strength in his arms, and began to experience a wide variety of difficulties as the disease ran roughshod over his body. Sonja Hayes, Scott’s wife of many years, carried him to countless doctor’s appointments as they vainly tried to find something that would stop the progression of the disease. Nothing worked to stave off the effects of the disease, which is also commonly called Lou Gehrig’s disease. Ultimately the disease won, and Scott lost his fight with the disease on July 3, nearly four years after his initial diagnosis. He was 53 years old when he died.

ALS (amyotrophic lateral sclerosis) is a progressive neurodegenerative disease that affects neurons in the brain and the spinal cord. The disease is usually fatal within two to five years of diagnosis. Patients with ALS lose the ability to control muscle movement, which eventually leads to total paralysis and then death. Currently, there is no known cure for the disease. The Centers for Disease Control and Prevention (CDC) estimates that approximately 12,000 to 15,000 Americans have ALS, with about 5,000 to 6,000 diagnosed annually.

While there is no cure for the disease, multiple companies are working on treatments, hoping to be the first to provide a viable option for patients like Scott Hayes. There are some treatments that may provide hope for patients.

Last year, Mitsubishi Tanabe and its new subsidiary, MT Pharma America, secured regulatory approval for Radicava, the first ALS drug approved in 22 years. Radicava is not a cure for ALS, but slows decline in the daily functioning of ALS patients. The drug was approved based on Phase III clinical trials that demonstrated patients taking the drug had a slower decline in physical function than those taking the placebo. Data demonstrated patients who received Radicava for six months experienced significantly less decline in physical function — by 33 percent.

Since its approval, Kevin O’Brien, MTPA’s vice president of market access, told BioSpace that the company has had some hurdles to overcome since approval of Radicava. Issues have included insurance hurdles and the establishment of infusion centers across the U.S.

In addition to Radicava, there is one other medication approved by the U.S. Food and Drug Administration (FDA) for ALS – Sanofi’s Rilutek (riluzole). It was the first drug approved by the FDA to treat ALS. Like Radicava, it’s no cure for ALS, but can slow progression of the disease.

One treatment currently in development that is generating a lot of buzz is BrainStorm’s NurOwn. Israel-based BrainStorm’s treatment has the potential to be the first ALS therapy to improve patient functioning as a regenerative medicine. Similar to CAR-T therapies, BrainStorm’s NurOwn uses a patient’s own cells which have been engineered outside the body, to produce and secrete factors known to promote neuronal survival. BrainStorm’s experimental treatment was one of the drugs that was a driver in the passage of the federal Right-to-Try legislation. Although not yet approved, some ALS patients hoped the treatment would be made available to them outside of the clinical trial parameters as a potential treatment. That hope was based on Phase II trials that showed NurOwn slowed the progression of the disease following multiple dosings. The Phase III trial is expected to be completed in July 2019, according to the government’s clinical trials database.

Mitsubishi Tanabe, the maker of Radicava, teamed up with Amgen to back the launch of Cambridge, Mass.-based QurAlis, which is developing three therapeutics targeting subsets of ALS. The company is developing treatments that include: a transformative device to remove toxic proteins; a drug that mediates overactive neurons and prevents them from dying; and a drug that restores a dysfunctional waste clearance system in cells.

While some pipeline treatments show potential for patients, some experimental drugs have not lived up to hope. Case in point, last year South San Francisco-based Cytokinetics scrapped a late-stage ALS drug after it flunked a Phase III trial. Tirasemtiv failed in the Phase III VITALITY-ALS trial to differentiate itself from placebo in a statistically significant manner. Where tirasemtiv failed, Cytokinetics suggested last year that its fast skeletal muscle activator, CK-2127107 (reldesemtiv), could be a potential treatment for ALS. Phase II results are expected this year.

As drug companies continue to develop potential treatments and one day, a hopeful cure, ALS diagnoses are expected to increase. The number of diagnoses is expected to grow globally more than 69 percent by 2040 to an expected 376,674 patients.

https://bit.ly/2PcT4OQ

RBC Downgrades Intercept On Valuation, Remains Positive On Upcoming Trial Data

Following the 90-percent year-to-date appreciation in Intercept Pharmaceutical, Inc. ICPT 8.46% shares, RBC Capital Markets considers the stock’s risk-reward to be balanced.

The Analyst

RBC Capital Markets analyst Brian Abrahams downgraded Interceptfrom Outperform to Sector Perform with a $115 price target.

The Thesis

RBC remains positive on the company’s Regenerate trial for patients with advanced liver fibrosis, Abrahams said in the Wednesday downgrade note. (See the analyst’s track record here.)

“ … We continue to believe the interim REGENERATE analysis [the first half of 2019] is more likely than not to be positive,” the analyst said.

The balanced reward-risk valuation is driven by the considerable rise in share price, Abrahamssaid. While expectations for trials such as REGENERATE and NASH have not altered, the analyst said they were overly discounted before the run-up.

Peer NASH company valuations illustrate similar expectations, Abrahams said.

“Interestingly, we note that the gap in valuation between ICPT and Madrigal Pharmaceuticals Inc MDGL 1.31% has closed … further suggesting we may have reached a more balanced relative level.”

https://bit.ly/2MmlPLq

MiMedx Provides Additional Information and Context to Wall Street Journal Article

MiMedx Group, Inc. (NASDAQ: MDXG), a leading developer and marketer of regenerative and therapeutic biologics, today provided additional background and context to certain points, including third party statements, in an article published by The Wall Street Journal (‘WSJ’) on August 14, 2018:

MiMedx products are manufactured according to current Good Tissue Practices (cGTP) standards, pursuant to the Food and Drug Administration (‘FDA’) regulations specified in 21 CFR 1271, which are the requirements and guidelines the Company must follow. MiMedx is also in compliance with the American Association of Tissue Banks’ 14th standard, of which the Company is a fully accredited member in good standing.

In addition, certain MiMedx products are marketed as cellular and tissue based products (‘HCT/Ps’) under Section 361 of the Public Health Service Act until either a biologics license application (‘BLA’) by the Company is approved or the FDA’s enforcement discretion under the November 2017 guidance document¹ ends. Since the 2016 inspection report from the FDA referenced by the WSJ, MiMedx has continued its transition to cGMP compliance for certain products as it conducts clinical trials to seek approval for certain indications under a BLA filing for its micronized dehydrated Amnion/Chorion Membrane (‘dHACM’) injection (AmnioFix® Injectable).

In terms of the clinical evidence supporting the Company’s products, MiMedx continues to build its compendium of clinical studies, including numerous randomized controlled studies, to support the use of EpiFix®. In addition, the Company has three ongoing investigational new drug programs with the FDA covering clinical studies intended to support an eventual BLA for micronized dHACM injection. As an example, interim results from a Phase 2B multicenter, randomized controlled trial evaluating the use of micronized dHACM injection as a treatment for Plantar Fasciitis were recently published in Foot and Ankle International. The interim results reflected statistically significant improvement in pain and foot function compared to the placebo control group. MiMedx also began enrolling patients into its Phase 3 Plantar Fasciitis trial in January 2018.

Selling micronized amniotic tissue-based products is a broad industry matter now covered by a finalized guidance document¹ from the FDA on homologous use and minimal manipulation of HCT/Ps. The guidance stated that all micronized amniotic products would require a biologics license to be lawfully marketed in the United States, and that FDA would use its enforcement discretion to provide a 36-month transition period. MiMedx is committed to the transition process as described in the November 2017 guidance. In the meantime, and until the end of the transition period, MiMedx continues to sell its micronized allograft products as HCT/Ps in the United States.

MiMedx continues to make progress on its market expansion objectives and clinical trial programs while continuing to maintain positive operating cash flow with no outstanding long-term debt. The Board and management team remain focused on positioning MiMedx to capitalize on the full array of opportunities presented by the Company’s processing capabilities, clinical science, customer relationships and scale.

As previously disclosed, the MiMedx Audit Committee is conducting an independent internal investigation into current and prior-period matters concerning sales and distribution practices and other matters. The Audit Committee is working diligently with its advisors to complete the investigation, and the Company is also working to prepare its financial statements for audit and regain compliance with Securities and Exchange Commission reporting obligations as soon as practicable.

https://bit.ly/2w8RDrX

Hikma Pharmaceuticals sees higher full-year revenue

London-listed Hikma Pharmaceuticals expects higher full-year revenue after raising forecasts at its top injectables and generics businesses, sending its shares up 10 percent.

The Jordanian drugmaker said it sold more injectable opioids in the United States due to a supply shortage, and had a better-than-forecast performance in generics for the first half of the year as its prices proved more resilient than expected.

The higher forecast in generics comes as global generic drugmakers with operations in the U.S. cut profit forecasts because of pricing pressure.

Novartis said last month that 2018 sales at its generics unit, Sandoz, would fall in the low single-digit percentages, after previously holding out hopes for them to remain steady.

Earlier this month, Mylan reported a much smaller-than-expected second-quarter profit and lowered its 2018 earnings forecast.

U.S. President Donald Trump has called for drug companies to lower prices and has set an agenda to do so.

Hikma, which makes and markets branded and non-branded generic and injectable drugs in more than 50 countries, reported 54 percent higher first-half operating profit, while revenue rose 11 percent.

Hikma’s U.S. injectables division – its largest unit – has been prioritising the manufacture of opioid products affected by shortages including fentanyl, meperidine, morphine and hydromorphone.

Injectable opioid painkillers, which hospitals use to manage pain after operations and in terminal illness, have been in short supply for more than a year largely due to production problems at Pfizer, the biggest supplier of the drugs.

Chief Executive Sigurdur Olafsson, who replaced Said Darwazah in February, said in a call with Reuters that Hikma’s reputation among hospitals has improved as it increased production of opioids to relieve shortages.

However, the company said it will not see the same demand for some injectables next year as Pfizer said it was confident that it would resolve issues at its plant.

Shares of Hikma rose as much as 10 percent to 1,812.5 pence in early trading, their highest in more than a year. The company was the biggest gainer on the mid-cap FTSE 250 index <.FTMC>.

Hikma expects full-year revenue at its injectables business to be $775 million (608.9 million pounds) to $825 million (648.3 million pounds), higher than its prior forecast of $750 million (589.3 million pounds) to $800 million (628.6 million pounds), while margins are seen in the mid to high 30s percent, up from low-to-mid 30s percent.

In generics, it expects revenue to be $600 million to $650 million, up from $550 million to $600 million, and margins to be mid-to-high single digits, up from low single digits.

Hikma, which was forced to cut revenue guidance for its generics business three times in 2017 due to pricing pressures, has seen some relief in the market.

“I think it’s a little better (now)”, said Olafsson, noting that Hikma saw high-single-digit price erosion in the first half of the year compared to a double-digit last year.

https://bit.ly/2Bh42Qw

MiMedx: Health Insurer Shuns ‘Unproven’ Amniotic-Tissue Products

United Healthcare, one of the nation’s largest insurance companies, has determined that amniotic tissue products made by MiMedx Group Inc. and other manufacturers are “unproven and/or not medically necessary for any indication,” and won’t reimburse patients for their use, according to the insurer’s most recent medical policy update bulletin.

The updated policy at United Healthcare, which goes into effect Oct. 1, came about because of “insufficient clinical evidence of safety and/or efficacy in published peer-reviewed medical literature” about the products, the bulletin said.

“Due to limited studies, small sample sizes, and weak study designs, there is insufficient clinical evidence to conclude that these skin substitutes have an improved health outcome over standard therapies; well-designed, randomized comparative clinical trials are needed to demonstrate the efficacy and safety of these products,” United Healthcare said.

“Unlike many other insurers, UnitedHealthcare has not covered MiMedx products, so this does not represent a change in coverage,” said a MiMedx spokesman. “We look forward to continuing to build on our compendium of clinical studies to help gain coverage in the future.”

The products, which include wound patches and injectable products made of amniotic tissue, have been aggressively promoted to treat a variety of ailments, including erectile dysfunction, osteoarthritis and hair loss.

The decision by the giant insurer, whose parent company is UnitedHealth Group Inc., hasn’t been publicly reported and coincides with a similar policy change by Health Care Services Corp., the parent of Blue Cross/Blue Shield operations in five states.

On Aug. 1, Health Care Services said it wouldn’t reimburse patients for injectable amniotic-tissue products, saying they are experimental and investigational. It also said it would limit reimbursement for wound patches made from the material.

After The Wall Street Journal reported on that change, MiMedx issued a news release Wednesday saying the company “continues to build its compendium of clinical studies, including numerous randomized controlled studies, to support the use of EpiFix,” an amniotic skin graft.

Once a highflying health-care company, MiMedx is facing an array of woes. It is in the process of restating its financial results back to 2012, and its founder, Parker H. “Pete” Petit, has been removed as chief executive, although he remains on the board. Its shares, which peaked at nearly $18 earlier this year, have fallen to below $4.

The company prospered after it acquired a seller of treatments in 2011 meant to heal wounds more quickly. The products, made from placentas from women who have given birth by caesarean section, were lightly regulated and relatively inexpensive to make.

MiMedx takes the amniotic membrane — thin, moist tissue that protects the fetus — and processes it into wound patches or grinds it into a powder that can be applied topically or by injection.

A recent Wall Street Journal investigation detailed allegations by former employees that MiMedx improperly booked revenue when it shipped goods, rather than when the products were used. Its practices are under investigation by the Justice Department, the Department of Veterans Affairs and the Securities and Exchange Commission.

The Marietta, Ga.-based company has said its board’s audit committee is conducting an independent investigation into “certain sales and distribution practices and other matters” and that it is cooperating fully with regulatory agencies, but didn’t elaborate.

https://bit.ly/2KWPHZ5