Alzheon Takes Another Shot at an IPO

In April, Alzheon attempted an initial public offering (IPO) to raise $80 million, but withdrew the offering. It has decided to try again, filing with the U.S. Securities and Exchange Commission (SEC), indicating it planned to raise $40 million in an IPO.

The company is working in the high-risk category of Alzheimer’s disease. Its lead product candidate is ALZ-801, an orally-administered inhibitor of beta-amyloid misfolding. Beta-amyloid is believed to be the primary cause of memory loss and cognition problems associated with Alzheimer’s disease, and most drug candidates for the disease focus on preventing or clearing beta-amyloid. However, numerous failures have cast doubt on the amyloid theory.

In the prospectus, Alzheon notes, “We believe that we are the only company developing a clinical stage small molecule with a mechanism of action designed to prevent the misfolding and aggregation of beta amyloid protein into neurotoxic oligomers. If ALZ-801 is approved, we believe it has the potential to be among the first drugs to intervene in a key underlying mechanism of Alzheimer’s disease, or AD. The active ingredient of ALZ-801, tramiprosate, was evaluated in 16 clinical trials conducted by BELLUS Health (formerly Neurochem), or Bellus, including trials in AD, with over 2,000 patients. In these trials, a favorable safety profile was observed, and in our post hoc analyses of data from these trials, we observed promising clinical signals in a subset of patients with two copies of the APOE4 gene, or APOE4/4 homozygotes, who have greater beta amyloid burden and develop AD earlier.”

The company hopes to use the funds raised to launch a Phase IIb clinical trial of ALZ-801 in the first half of 2019 in the U.S., and possibly internationally. It also expects to start a Phase Ib clinical trial to evaluate the plasma pharmacokinetics (PK) of ALZ-801 in AD patients with one or two copies of the APOE4 gene later this year.

The April IPO bookrunners were Citi and Piper Jaffray. For this attempt, it is ThinkEquity. It expects to list on the Nasdaq under the symbol ALZH.

On July 23, Alzheon announced it was presenting data at the Alzheimer’s Association International Conference (AAIC) on July 25 describing new research on tramiprosate, the active ingredient in ALZ-801. One presentation indicated that more patients remained cognitively stable over 78 weeks on the drug based on the Alzheimer’s Disease Assessment Scale-Cognitive Subscale, reporting 57 percent on the drug and 20 percent for placebo. The second presentation indicated that more patients had minimal or no decline in function over 78 weeks of treatment based on the Disability Assessment for Dementia (DAD), with 46 percent on the drug and 18 percent on placebo.

“Responder rates in APOE4/4 patients with Mild AD support meaningful efficacy of tramiprosate in this population, and will help us design our planned confirmatory studies with ALZ-801,” said Susan Abushakra, Alzheon’s chief medical officer, in a statement at the time. “We continue to build on the body of clinical evidence to support the development of ALK-801, and we are enthusiastic to initiate the pivotal program with ALZ-801 for Alzheimer’s patients in need of effective treatment.”

https://bit.ly/2NuPMW9

U.K.’s NICE Rejects Gilead Sciences’ Yescarta Over the Drug’s Cost

The United Kingdom’s government-funded health service isn’t being so nice to Gilead Sciences’ CAR-T blood cancer treatment Yescarta. The country’s National Institute for Health and Care Excellence (NICE) said the therapy is too expensive for the agency to justify.

The announcement by the U.K. agency came one day after Yescarta (axicabtagene ciloleucel) received approval from the European Medicines Agency (EMA) for use across the European Union. Yescarta is the first CAR-T treatment in Europe to be approved for two types of aggressive non-Hodgkin’s Lymphoma. On Monday the CAR-T treatment was approved for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy. Each of the 28 European countries will be able to determine how their public-financed health agencies support Yescarta.

Back in the U.K. though, the drug will not be supported by the nation’s publically-funded healthcare agency. In its announcement, NICE said Yescarta “is not recommended, within its anticipated marketing authorization, for treating relapsed or refractory diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma in adults after two or more systemic therapies.” NICE added that the new guidance will not affect those patients who have already been treated with Yescarta prior to the publication of the new ruling. NICE said those patients can continue their treatment without change to funding arrangements already in place.

In the United States, treatment with Yescarta has a list price of about $373,000. It was first approved in the U.S. in October 2017. NICE did not provide an indication of how much the treatment would be in the U.K. CNBC reported that drug manufacturers typically provide discounts to the National Health Service as part of the approval process.

NICE also raised concern over the lack of comparator data. In its rejection, NICE said there is no standard treatment for relapsed or refractory diffuse large B-cell lymphoma or primary mediastinal large B-cell lymphoma in adults after two or more systemic therapies. NICE said that “best supportive care” usually include “salvage chemotherapy.”

NICE added that evidence from a “small, single-arm study” supports the efficacy of Yescarta. The agency said patients have good response rates and show progress in overall survival, as well as progression-free survival. However, NICE said there is no direct data comparing Yescarta with salvage chemotherapy (referred to as best supportive care by the company), NICE said.

“This means that the exact size of the benefit of axicabtagene ciloleucel compared with salvage chemotherapy is unknown,” NICE wrote in its guidance. “Axicabtagene ciloleucel meets NICE’s criteria to be considered a life-extending treatment at the end of life. However, all the cost-effectiveness estimates are above the range normally considered to be a cost-effective use of NHS resources.”

CNBC reported that Yescarta is the first CAR-T treatment to be assessed by the U.K.’s NICE. The agency is currently examining Kymriah, which is developed by Swiss pharma giant Novartis. The Novartis CAR-T drug was also approved by the EMA on Monday.

https://bit.ly/2oeNSxM

Biogen and Eisai Report Phase Ib Extension Data for Alzheimer’s Trial

Cambridge, Mass.-based Biogen and Tokyo, Japan-based Eisai announced results from an analysis of their ongoing long-term extension (LTE) Phase Ib trial of aducanumab for Alzheimer’s disease.

The current updated analysis included data from the placebo-controlled period and LTE for patients treated with the drug up to 36 months in the titration cohort and up to 48 months in the fix-dose cohorts. The companies report the data are generally consistent with previous interim data reports and there were no changes to the risk-benefit profile of the drug.

Aducanumab (BIIB037) is being studied in early Alzheimer’s disease. It is a human recombinant monoclonal antibody (mAb) made up of a de-identified library of B cells collected from healthy elderly patients with no signs of cognitive impairment or cognitively impaired elderly subjects with unusually slow cognitive decline. They were collected using Neurimmune’s technology platform, Reverse Translational Medicine (RTM). Biogen licensed aducanumab from Neurimmune. Since October 22, 2017, Biogen and Eisai have been collaborating on developing and commercializing aducanumab.

The Phase Ib clinical trial is a randomized, double-blind, placebo-controlled, multiple-dose trial to evaluate the safety tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and clinical effects of aducanumab in patients with prodromal AD or mild AD dementia. There are fixed doses of 1, 3, 6 and 10 mg/kg in addition to an arm with a titration regimen where patients are given gradually increasing doses of aducanumab until they hit 10 mg/kg.

In the Phase Ib trial, 196 patients received either aducanumab or placebo. Of those, 143 patients entered LTE. The LTE cohorts were divided across six dosing arms, which included placebo switchers, 1 mg/kg switchers to 3 mg/kg, fixed doses of 3, 6 and 10 mg/kg, and titration. There were expected discontinuations, which means there were fewer patient numbers in the new analyses.

Levels of amyloid beta plaque were measured by positron emission tomography (PET). Patients showed a decrease in a dose and time-dependent matter of amyloid levels from the titration cohort at 36 months and fixed-dose cohorts at 48 months.

There were exploratory clinical endpoints evaluated, including Clinical Dementia Rating Sum of Boxes (CDR-SB) and the Mini-Mental State Examination (MMSE). These data suggested a continued befit on the rate of clinical decline over 36 and 48 months.

The companies stated, “Of the 185 patients dosed with aducanumab in the Phase Ib study, 46 patients experienced amyloid imaging abnormalities (ARIA)-E (edema). Eight patients experienced more than one episode of ARIA-E. The majority of ARIA events occurred early in the course of treatment; they were typically mild radiographically (MRI), clinically asymptomatic and resolved or stabilized within 4-12 weeks, with most patients continuing treatment. In the Phase Ib LTE, the most commonly reported adverse events were headache, fall and ARIA.”

This announcement seems to have investors and analysts pausing. In late-July, the two companies disclosed data from their BAN2401 Alzheimer’s trial, which caused Biogen shares to drop slightly, largely based on some skepticism over their actual meaning of the results, which overall appeared positive. In that trial, patients taking the highest dose of the drug showed a 30 percent decrease in cognitive decline compared to placebo. And in the patients receiving the highest dose of BAN2401, 81 percent tested negative for amyloid after 18 months of treatment. But investors and analysts focused on the details, noting that patients on low doses of BAN2401 did not matter, and in some cases did worse, than patients receiving placebo. There was also concern that the companies had also excluded patients carrying the APO4 gene, which is linked to increased risk of late-onset Alzheimer’s.

Today’s stock, so far, is remaining largely unaffected by the news. Biogen shares opened at $344.42 and are currently at $343.34. Eisai took a little harder hit. It was trading at 9,962 yen for a high on August 27 and is currently trading at 9,743 yen.

https://bit.ly/2PHM2SF

Lonza to Highlight New ScreenLight™ Block at In-Cosmetics Latin America

• Recently launched bioactive functional ingredient helps protect skin from blue light and environmental stressors.

At In-Cosmetics Latin America, Lonza will feature its new Bioactive Functional ingredient, ScreenLight™ Block, which helps protect skin against the visible effects of blue light, UV light and pollution. In-Cosmetics Latin America will take place 19-20 September in São Paulo (BR). Lonza will be at Stand E30.

‘ScreenLight™ Block provides a powerful defensive shield against the visible skin aging effects of blue light and more,’ said Vanessa Arruda, PhD, Global Market Development Manager, Bioactives. ‘Consumers who use their cell phones and computers extensively can apply facial creams that not only mitigate the visible effects of the blue light emanating from their screens, but also help protect their skin against the effects of UV stress and pollution.’

Key Attributes

The recently launched ScreenLight™ Block helps protect skin against the visible effects of environmental stress factors in a number of ways. It:

• Helps reduce the appearance of dark spots, resulting in skin that appears more evenly toned (based on in vivo clinical data);
• Helps reduce the appearance of fine lines and wrinkles (based on subjects’ perceptions of themselves);
• Helps prevent increased melanin production from exposure to visible light and pollution (based on ex vivo data); and
• Helps protect skin against the visible effects of light exposure by reducing the negative impact on cellular antioxidant potential (measured by superoxide dismutase, or SOD, expression); elastin, fibrillin, microfibrillar-associated protein 4 (MFAP4) and metalloproteinase-1 (MMP-1, based on ex vivo & in vitro data).

Arruda noted that environmental stressors can degrade unprotected skin and reduce the availability of MFAP4, fibrillin and elastin, leading to loss of elasticity, skin photo-aging, worsening wrinkles, fine lines and hyperpigmentation.

Third-party in vitro testing showed that ScreenLight™ Block acts differently under different stress conditions. Under visible light and under conditions of artificial pollution, the bioactive decreases melanin synthesis in the skin. Under UV stress ScreenLight™ Block protects collagen and increases skin elasticity. Clinical trial results showed that ScreenLight™ Block helps reduce the appearance of dark spots, resulting in skin that appears more evenly toned, and helps reduce the appearance of fine lines and wrinkles.

https://bit.ly/2BVvtQh

Roche diagnostics head exits

 Roche diagnostics head Roland Diggelmann is resigning as of Sept. 30, ending a 10-year stint at the Swiss drugmaker and for now leaving the business with 12.1 billion Swiss francs ($12.15 billion) in sales without a permanent leader.

Michael Heuer, head of Roche Diagnostics for Europe, the Middle East, Africa, and Latin America, will take over on an interim basis until a replacement is named, Roche said on Tuesday.

Diggelmann, 51, arrived at Roche from the medtech industry in 2008, having held executive roles at Swiss hip maker Sulzer Medica before and after it was purchased by Zimmer.

Since 2012 he has led Roche’s diagnostics unit, which makes equipment and sophisticated tests for diseases but has also been held back in recent years by its sluggish diabetes business.

Diagnostics accounts for more than 20 percent of Roche’s annual sales, and is seen as playing an increasingly important role in tests to determine the effectiveness of cancer immunotherapy.

Roche said Diggelmann would “pursue his career outside of the company”. Diggelmann could not immediately be reached for comment.

“I wish him all the best for the future,” Chief Executive Severin Schwan said in a statement.

For years, Diggelmann has been Roche’s point person in countering persistent suggestions the company would unload diagnostics’ diabetes business, even as others including Johnson & Johnson and Bayer exited amid increased competition and public-sector medical insurers’ steady pressure to cut reimbursements.

A two-decade Roche veteran, Heuer was a longtime Boehringer Mannheim employee before Roche bought the German diagnostics-and-drug company in 1998.

Since then, the trained chemist has held roles in sales, marketing and product development in Germany, Austria and the United States. He will become a member of the corporate executive committee.

“Michael is a very respected leader with a wealth of experience in diagnostics,” Schwan said.

https://bit.ly/2oicWEb

Mo. smoke bans may hit casinos: Jefferies

Voters in St. Charles County will be able to vote on two alternative indoor smoking bans in the Nov. 6 election – one that would continue to allow indoor smoking at cigar bars, tobacco stores and private clubs and another that would allow even more exceptions – while St. Louis County voters will only be voting on a strong indoor smoking ban with almost no exceptions except for private residences, reported the St. Louis Post-Dispatch. Jefferies analyst David Katz has said the proposed smoking bans could be potentially detrimental to casino operators Penn National (PENN) and Boyd Gaming (BYD).
https://bit.ly/2MZlEoK

You May Start Seeing Drug Prices In Ads, But Will You Understand The Point?

Late last week, the U.S. Senate passed an amendment to the spending bill that would require pharma companies to disclose the prices of any products they advertise directly to consumers. The package devotes $1 million in funding to implement the new requirement, which co-sponsoring Senator Chuck Grassley (R-Iowa) believes will be vital for bringing “transparency to drug pricing and educating the public about the cost of their prescriptions,” he said in a statement.

This idea has been floating around since early May, when President Donald Trump suggested it as a way to lower prescription drug costs. Shortly after that, FDA Commissioner Scott Gottlieb acknowledged he had put together a working group to examine the intricacies of implementing such a requirement.

But questions abound, not the least of which is this: Which price would drug makers be required to disclose in their direct-to-consumer (DTC) ads? Would it be the list prices that are provided to insurers, the price they pay after rebates or the suggested retail price? Regardless of what the answer ends up being, there’s the nagging question of whether this information would actually mean anything to consumers, or if it would just confuse them, considering the fact that their actual out-of-pocket price would be set by their health insurer.

For now, the most popular idea is to include the list prices of drugs in ads. For the world’s top-selling drug, AbbVie’s Humira for rheumatoid arthritis and other diseases, that would be an estimated $50,000 a year or so. And it’s a number viewers could see quite often: More than 6,000 TV ads for Humira have run in the last month alone, according to real-time ad tracker iSpot.TV.

Despite the fact that few consumers actually pay full prices for drugs, there’s significant support for the idea of providing some information about cost in DTC ads. Last year, the American Medical Association adopted a policy calling on prescription drug manufacturers to include the suggested retail price in drug ads, suggesting it would offer a way to bring attention to rapidly rising costs.

“Sunlight is needed to help respond to price shifts, because if the pricing trends continue, patients and communities will not be able to afford life-saving drugs,” said now AMA President Barbara McAneny, M.D., in a statement.

The “sunlight” concept has long been attractive to Grassley. He authored the Physician Payments Sunshine Act, which requires drug and device companies to disclose payments they make to doctors. The idea was to encourage self-policing in the industry, fueled by a desire to not have to disclose transactions that could be viewed as conflicts of interest.

A similar pattern of thinking is at work with the drug-price proposal. “What Senator Grassley and I wanted to do is to give the American people more information about drug costs,” said the co-sponsor of the newly passed amendment, Dick Durbin (D-IL), in the statement. “More information gives transparency to the transaction, and will help give American consumers a break and start to slow down the skyrocketing cost of prescription drugs.”

The idea seems to have broad support from the public, too. In late June, the Kaiser Family Foundation released a poll showing that 76% of people think the federal government should require drug manufacturers to disclose pricing information in ads. About half of respondents who said they had requested prescriptions for advertised drugs reported that their physicians did talk to them about cost issues.

But would price disclosure in DTC drug ads really bring down the prices of prescription drugs, as Durbin suggests? There certainly is not a linear relationship between disclosure and behavior change in this case, considering that a $50,000 drug may only cost the average consumer a couple hundred of dollars per year in co-pays.

As for the list prices that payers like pharmacy benefits managers (PBMs) are faced with, it’s unclear if any of Trump’s proposals are really having an impact. On August 17, Senators Elizabeth Warren (D-MA) and Tina Smith (D-MN) sent a letter to Alex Azar, secretary of the Department of Health and Human Services, expressing doubts about Trump’s claims that there would be a “major drop in the cost of prescription drugs” as a result of new policies.

Warren and Smith wrote to the six largest PBMs to gauge their progress in negotiating lower list prices for prescription drugs. CVS Health reported that they’ve had “very limited discussions” with drug companies about lowering prices, and that only Pfizer had made an actual commitment, and that was to reverse a price hike the company had been planning. Express Scripts said it hadn’t received any commitments from pharma companies saying they planned to lower their list prices.

https://bit.ly/2PMnPKQ