AnaptysBio’s lead IL-33 antibody clears midstage test in asthma

Next-generation antibody company AnaptysBio has positive data for its lead pipeline drug etokimab in a third indication, adding asthma to its earlier wins in peanut allergy and atopic dermatitis.

The phase 2a trial in severe eosinophilic asthma gives the San Diego company another proof-of-concept study for the interleukin-33 (IL-33) inhibitor, setting up a third phase 2b program that it sayswill start early next year. Shares in the company were down marginally after the announcement.

The study was small—involving just 25 patients who received a single intravenous dose of etokimab (ANB020)—but according to the company showed that the anti-IL-33 drug had a rapid impact on lung function that lasted for around two months.

Using the forced exhalation in one second (FEV1) measure, the trial showed an 8% improvement for the antibody compared to placebo the second day after dosing, and this rose to 11% by day 64, although the difference fell back to 4% and 6% at timepoints in between.

Blood biomarkers supported the proposed mechanism of the drug, with eosinophil levels down 31% at day two and 46% at day 64 versus control, though once again with dips in the interim. All the patients were also taking inhaled steroids and beta agonist bronchodilators.

The trial’s principal investigator—University of Oxford respiratory specialist Professor Ian Pavord—said the data shows “the potential for IL-33 inhibition in treating severe eosinophilic asthma” but will need to be investigated further in additional studies.

Earlier this year, AnaptysBio reported proof-of-concept data with etokimab in peanut allergy, once again with some questions about study in terms of its size and the San Diego biotech’s decision to exclude a couple of patients from the analysis, which improved the results.

In 2017, it reported data in atopic dermatitis which CEO Hamza Suria said were “a solid foundation for the continued development of [the drug] across a number of atopic diseases”—and helped the company complete a $195 million public offering to help fund its phase 2 programs, which will use a new subcutaneous formulation of the drug.

The company has two phase 2b trials on the go—ATLAS in atopic dermatitis and ECLIPSE in chronic rhinosinusitis with nasal polyps—that are due to read out in the second half of 2019, said Suria on a conference call.

With three separate studies now showing an impact on inflammatory diseases, the biotech is becoming increasingly confident that IL-33 is a target worth pursuing. Etokimab is pitching at increasingly competitive indications with atopic dermatitis and severe asthma however, as both diseases have new biologic therapies in the rollout phase.

“We are thrilled to have demonstrated proof-of-concept in this single dose Phase 2a trial and look forward to advancing the development of etokimab for patients suffering from eosinophilic asthma,” commented Suria, who says the biotech is out in front in the anti-IL-33 category.

“Genotypic studies have validated the key role played by IL-33 in asthma, and we believe etokimab’s upstream mechanism has the potential for a broad therapeutic benefit across multiple atopic disorders.”

https://www.fiercebiotech.com/biotech/anaptysbio-s-lead-il-33-antibody-clears-mid-stage-test-asthma

Tariffs now touch nearly every U.S. medical device sold in China

The trade war between the U.S. and China has grown in both size and scope—with Chinese retaliatory tariffs now reaching nearly every U.S. medical device exported to the country—while uncertainty over the years ahead has companies looking to prepare against larger impacts.

At midnight EST on Monday, Sept. 24, or noon in Beijing, the Trump administration imposed 10% tariffs on $200 billion worth of imports. At the same time, China returned with 5% to 10% tariffs on $60 billion of U.S. goods, including $3.5 billion in medtech-related trade.

Added to tariffs levied this past summer, the latest round totals nearly all U.S. medtech exports to China in 2017, or about $4.75 billion, according to AdvaMed, the industry’s trade association.

“Depending on where you are in the industry, the tariff situation and related activities will impact you differently,” AdvaMed CEO Scott Whitaker told reporters during a press event at the trade group’s annual conference. For example, companies in the imaging space may feel a more direct impact because of reliance on component parts, he said.

In addition, because of the disparity in the total dollar amounts between the two countries, China also threatened to impose extra, unspecified, non-tariff barriers with more qualitative effects—such as slow-walked regulatory approvals or possible investigations into various companies’ operations within the country.

Meanwhile, the latest $200 billion in tariffs on imports from China are slated to increase from 10% to 25% on Jan. 1, after the holiday shopping season. President Donald Trump has also called for an additional $267 billion in tariffs on top of that, totaling essentially all of China’s exports to the U.S., depending on the country’s actions going forward.

“As the number as gotten bigger, and as the back and forth between China and the U.S. has grown, we’re starting to see it impact us a little bit more,” Whitaker said. “When you get to $200 billion, and when you get to $267 billion, then you’re really starting to affect all aspects of the economy.”

AdvaMed is currently working to assess the tariffs’ impact by company and product category, and is aiming to release a report in the coming months, Whitaker said. China’s retaliatory tariffs first hit the industry directly in late August, with a matching $16 billion riposte against U.S. exports that included $1.25 billion against medtech products.

At the association’s conference in Philadelphia, Claire Reade, former assistant U.S. trade representative for China affairs, detailed companies’ options for navigating the new U.S. tariffs, such as applying for exclusionary waivers for specific products.

Companies would have to prove no comparable product exists outside of China, that Chinese supply has been critical to the company’s efforts over the past several years and that losing that access would cause severe harm.

In addition, the product has to be physically distinct from other products under the same tariff category—trademarks or logos are not enough, said Reade, who also served as the Office of the U.S. Trade Representative’s chief counsel for China trade enforcement. She is now a senior counsel at the law firm Arnold & Porter.

Aside from that, three options include absorbing the tariffs, such as by building up the company’s stock of products; adjusting procurement to other locations, including non-Chinese plants from a Chinese supplier or from other parts of the world; or by changing the company’s manufacturing footprint through shifts to contract manufacturing or setting up new plants, said Rene Buck, CEO of Buck Consultants International.

But what should companies not do? “There are a bunch of Chinese companies today on the internet that will offer to bring your products to Malaysia, label them as ‘Made in Malaysia’ and then send them over,” Buck warned of the illegal bypass. “You could imagine cases where that might be appealing, but probably we both agree it’s not what you should do, right?”

Reade added: “Criminal customs fraud. Prison. Major fines. Okay? Okay.”

https://www.fiercebiotech.com/medtech/trade-war-tariffs-now-touch-nearly-every-u-s-medical-device-sold-china

Thousands of deaths from infected NHS blood probed

A public inquiry has opened to look into how infected NHS blood killed more than 2,900 people since the 1970s.

The Infected Blood Inquiry, headed up by Sir Brian Langstaff, a former high court judge, was announced in July last year following years of campaigning by those affected, their families, and organisations.

It began today with a tribute to the many individuals who were given transfusions or treatments with blood infected with the HIV virus and hepatitis C.

The inquiry into the scandal, which was dubbed ‘the worst treatment disaster in NHS history’, will address how the blood was obtained and came to be used for people with haemophilia and other bleeding disorders.

Some patients had transfusions of the infected blood plasma whereas others were injected with blood-clotting protein Factor VIII, which haemophiliacs do not produce naturally.

Much of the human blood plasma used to make the product came from donors such as prison inmates, sex workers and drug addicts based in the US, who sold their blood. This was to meet a shortfall in the amount of blood available in the UK.

Blood products were not routinely heat-treated until the mid-1980s to kill any viruses. Screening of blood products began in 1991 and by the late 1990s, synthetic treatments for haemophilia were available, removing the infection risk.

Many sufferers remained quiet about the illnesses contracted through the infected blood products because of the historic stigma attached to HIV and hepatitis C.

The first evidence will be heard after Easter next year, with the process expected to last between two and five years. The inquiry will consider statements from hundreds of witnesses and experts.

Sir Brian Langstaff said: “The inquiry has already received over 100,000 documents and expects to acquire several times that number. There will also be many hundreds of witness statements. I am grateful for each and every contribution.

“There must, however, still be more who have knowledge, documents and their own accounts to add. I know that going over the past can be difficult, but I encourage them to come forward.”

Previous inquiries failed to address the issue adequately and the government has been accused of covering up the scandal, with former health secretary Andy Burnham reportedly saying in the House of Commons last year that there had been a “criminal cover-up on an industrial scale”.

https://pharmaphorum.com/news/public-inquiry-investigates-thousands-of-deaths-from-infected-blood-on-nhs/

Patients call for end to UK drug price row over cystic fibrosis med

Representatives of NHS England and cystic fibrosis drug company Vertex are to meet on Thursday to try and resolve a two-year impasse over access to life-changing medications.

Charities and patients called for a resolution to the ongoing pricing row, which began two years ago when NICE said Vertex’s combination therapy Orkambi (lumacaftor+ivacaftor) is too expensive for the NHS.

Orkambi is the first medicine to treat the underlying cause of cystic fibrosis in people with two copies of the F508del mutation, aged six or over, and Vertex has other drugs in its pipeline that will mean a wider group of patients will get treated.

NHS England and Vertex have been locked in an increasingly bitter argument over pricing, with the manufacturer accusing the NHS of undervaluing cystic fibrosis patients.

Vertex is trying to get the NHS to fund all its approved CF drugs, and any future medications in its pipeline in a long-term deal.

In July Vertex said it received an offer worth about £500 million over five years, and more than £1 billion over 10 years for Orkambi.

This was rejected and Vertex has made veiled threats that it will consider spending its R&D budget elsewhere because of the row.

It has also refused to engage with NICE until the cost-effectiveness body changes its assessment methods.

David Ramsden, chief executive of the Cystic Fibrosis Trust has written to Vertex’s chief executive Jeffrey Leiden, and NHS England’s chief executive Simon Stevens calling for the matter to be resolved.

Ramsden urged Leiden to do “everything in [his] power” to reach an agreement, while calling on Stevens to find a way to “value and reward” the innovative drugs from Vertex.

The UK has the second largest population of patients with CF in the world, with around 10,000 people affected.

Christina Walker with Luis

Christina Walker, from the patient group UKneedsorkambi, said the drug should be made available as soon as possible so that patients such as her son Luis can receive it.

Walker said: “It’s been a devastating summer for the campaign group while this impasse has persisted. We’ve watched our loved ones’ health decline with exacerbations, made many hospital visits and have mourned CF angels who’ve lost their final battle.

“Whether or not this situation continues unchecked is in the hands of the people from Vertex and the NHS around the table on Thursday.

“They must both compromise heavily – more than they want to – because lives are at stake and what’s the alternative? Too many people have died already. These transformational treatments can reduce the considerable suffering of this cruel condition, and patients must have them now. Time is up, and any further delay will be unforgivable.”

https://pharmaphorum.com/news/patients-call-for-cf-drug-price-agreement-ahead-of-meeting/

Antibiotics Safe for Appendicitis, 5-Year Follow-up Data Show

Antibiotics may be a feasible alternative to surgery for patients with uncomplicated acute appendicitis, 5-year follow-up data from a randomized trial show.

“Long-term follow up of patients with uncomplicated acute appendicitis suggests that initial treatment with antibiotics rather than surgery may be a feasible alternative,” write Paulina Salminen, MD, PhD, from the University of Turku, Finland, and colleagues. The researchers published the results online today in JAMA.

Although appendectomy has been the mainstay of treatment for acute appendicitis for more than 100 years, recent advances in diagnostic imaging and antibiotic therapies have allowed clinicians to consider antibiotic treatment as a viable alternative strategy in some cases.

In a recent randomized clinical trial, Salminen and colleagues found that 73% of all patients with acute uncomplicated appendicitis who received antibiotics alone did not require surgery at 1-year follow-up. However, questions remained regarding the long-term outcomes for these patients.

With this in mind, Salminen and colleagues sought to investigate the long-term recurrence rate among trial participants. The randomized Appendicitis Acuta trial was conducted at 6 hospitals in Finland and enrolled 530 adults (329 men; 201 women) with uncomplicated acute appendicitis. Of those, 273 underwent appendectomy (median age, 35 years) and 257 initially received antibiotic treatment (median age, 33 years).

With 5 years of follow-up, 3 patients had died: 2 in the appendectomy group and 1 in the antibiotics group. However, none of the deaths was considered related to the trial.

Among the 257 patients who initially received antibiotics, 100 underwent appendectomy during follow-up. Of those, 70 experienced their recurrent appendicitis within 1 year of the first episode (27.3%; 95% confidence interval [CI], 22.0% – 33.2%; 70/256), and 30 patients required an appendectomy at between 1 and 5 years (16.1%; 95% CI, 11.2% – 22.2%; 30/186).

The cumulative incidence of recurrent appendicitis among patients who initially received antibiotics alone was 34.0% (95% CI, 28.2% – 40.1%; 87/256) at 2 years, 35.2% (95% CI, 29.3% – 41.4%; 90/256) at 3 years, 37.1% (95% CI, 31.2% – 43.3%; 95/256) at 4 years, and 39.1% (95% CI, 33.1% – 45.3%; 100/256) at 5 years

“Nearly 2/3 of all patients who initially presented with uncomplicated appendicitis were successfully treated with antibiotics alone and those who ultimately developed recurrent disease did not experience any adverse outcomes related to the delay in appendectomy,” the authors write.

“These findings demonstrate the feasibility of treating appendicitis with antibiotics and without surgery,” Salminen and colleagues conclude.

In an accompanying editorial, Edward H. Livingston, MD, deputy editor at JAMA, emphasizes that one of the most important findings from this study is that patients in the antibiotics group who eventually needed surgery experienced no major complication because of delaying surgery.

“The findings from the [Appendicitis Acuta] trial dispel the notion that uncomplicated acute appendicitis is a surgical emergency,” he emphasizes. “Given that access to a surgeon is not always available, these results may have implications in many different settings and in many different countries.”

Future studies should address factors such as the optimal regimen to use for antibiotic treatment of appendicitis, says Livingston, as well as how to manage suspected recurrent appendicitis in patients who initially receive antibiotics alone.

In the AAPAC trial, patients in the antibiotics group received ertapenem (1 g/day) intravenously for 3 days while in hospital, followed by 7 days of levofloxacin (500 mg, once daily) and metronidazole (500 mg, 3 times daily). However, Livingston explains that this regimen is likely more aggressive than needed, and should be reevaluated.

The next step in appendicitis research should expand on the results from this trial to enhance nonsurgical treatment of appendicitis, he continued. “Further studies should be designed using a noninferiority approach, comparing different antibiotic approaches to that used in the [Appendicitis Acuta] study,” he concluded.

This study was supported by the Mary and Georg C. Ehrnrooth Foundation, a government research grant (EVO Foundation) awarded to Turku University Hospital, and a Turku University research grant. Salminen has reported receiving personal fees for lectures from Merck, Lilly, and Orion Pharma. The remaining authors and the editorialist have reported no financial conflicts of interest.

JAMA. Published online September 25, 2018.

https://www.medscape.com/viewarticle/902460

Insulin prices could be much lower; drug makers would still make healthy profits

As prices for diabetes treatments continue to roil consumers, a new study suggests that manufacturers could make both human and analog insulins at low costs and still pocket a profit.

After analyzing expenses for ingredients, production, and delivery, among other things, the researchers contend that the price for a year’s supply of human insulin could be $48 to $71 a person and between $78 and $133 for analog insulins, which are genetically altered forms that are known as rapid or long-acting treatments. Examples of analog insulins include Humalog, Lantus, and Novolog.

Put another way, the study estimated the cost of production for a vial of human insulin is between $2.28 and $3.42, while the production cost for a vial of most analog insulins is between $3.69 and $6.16, according to the study in BMJ Global Health.

Meanwhile, the median prices paid by more than two dozen countries for human insulin were 1.2 to 1.8 times greater than estimated prices. Median prices for other types of insulin were also higher: Lantus, which is sold by Sanofi (SNY), was 5.6 to 7.8 times higher; Humalog, which is sold by Eli Lilly (LLY), were at 2.7 to 3.7 times higher; and Novolog, a Novo Nordisk (NVO) treatment, was 2.6 to 3.5 times greater.

The study authors, who cited a 2016 study that examined government procurement prices paid and other data, argued their findings suggest greater competition would lead to sizable savings in most countries. They also maintain that existing insulin makers could set “significantly lower prices while still making a profit,” but they concede more companies would have to enter the market for this to occur.

“Anyone with Type 1 diabetes should be able to buy insulin for under $100 per year, including the long-acting forms,” said Andrew Hill, a study co-author and senior visiting research fellow at the University of Liverpool. “Pharmaceutical companies cannot justify charging governments $532 per person per year in the U.K. and $1,251 in the U.S., let alone similar amounts in low- and middle-income countries.”

There were some limitations to the study, though. For instance, biosimilar manufacturing expenses were not individually considered, such as capital expenditures, quality assurance and control, registration costs, and costs for adhering to manufacturing regulations. But the authors insisted they made a conservative assumption for the total costs of bringing a biosimilar to market.

A Sanofi spokeswoman wrote us that the drug maker “shares concerns about the affordability of medicines and is focused on ensuring people who can benefit from our medicines have access to them. As the authors noted, there were several limitations to the analysis, including a large number of assumptions which makes it challenging to draw any conclusions.”

[UPDATE: A Novo Nordisk spokesman sent us this: “We recognize that there are those who are having difficulty affording their medicine, including those made by us. We also appreciate the different perspectives across many stakeholders.  The affordability of insulin for patients depends on health systems, regardless of country. Globally, We have preferential pricing for low income countries but we’re aware that sometimes our medicines don’t reach patients because of inefficiencies and supply chains. In the U.S., we offer human insulin through several channels for approximately $25/vial.

“This study presents only one facet of the cost of medicines – the manufacturing process. It’s important to see the big picture and take a more holistic view including how the sales of the medicines fund broader R&D efforts for the next generation of medicines along with our manufacturing investments (such as our $2 billion expansion in the U.S.) when assessing cost.”]

We asked Lilly for comment and will update you accordingly.

The findings come amid ongoing controversy over the cost of diabetes treatments, which make an attractive target, given soaring prices.

A 2016 study in the Journal of the American Medical Association found the price for a milliliter of insulin climbed 197 percent from $4.34 per to $12.92 between 2002 and 2013. Two Washington lawmakers subsequently accused the three largest insulin makers — Lilly, Sanofi, and Novo Nordisk — of price collusion. The companies later publicly committed to limiting price hikes on their medicines.

Meanwhile, Nevada legislators made diabetes medicines the specific target of a transparency law that requires drug makers to report pricing histories, disclose costs, and notify state officials and insurers in advance of price hikes above inflation. The move was prompted by data showing high disease rates and the subsequent medical and economic costs to many states.

The study is likely to further embolden advocacy groups that have been trying to pressure drug makers to lower prices. In the U.S., T1 International and People of Faith for Access to Medicines are staging another demonstration this coming Sunday at Lilly headquarters in Indianapolis to protest insulin prices.

“It is unacceptable that governments and people are paying so much more than the cost of production for insulin. Estimating the cost of production for hepatitis C treatment was instrumental in getting dramatic price cuts. This needs to happen now for insulin,” said Dr. Margaret Ewen, global pricing coordinator for Health Action International, a nonprofit advocacy group that backed the study.

Indeed, the same researchers have conducted similar studies suggesting that production costs for other types of medicines were sufficiently low enough that manufacturers could slash prices and still make reasonable profits to satisfy financial goals. This work was regularly cited by patient advocates who sought to pressure drug makers to lower their prices in order to widen access to treatment, especially in low-income countries.

In reaching their conclusions, the researchers used pricing data for active pharmaceutical ingredients exported from India and price quotes from insulin makers. When API pricing could not be obtained, prices were estimated based on comparison of similarity, in terms of manufacturing process, with APIs for which prices were available. Potential biosimilar prices were estimated by adding costs of excipients, formulation, transport, development and regulatory costs, and a profit margin.

https://www.statnews.com/pharmalot/2018/09/25/insulin-prices-profits-diabetes/

Alzheimer’s biotech Alzheon sets terms for $35 million IPO

Alzheon, a Phase 3 biotech developing small molecule therapies for Alzheimer’s disease, announced terms for its IPO on Tuesday.

The Framingham, MA-based company plans to raise $35 million by offering 2.5 million shares at a price range of $13 to $15. At the midpoint of the proposed range, Alzheon would command a fully diluted market value of $196 million.

Alzheon was founded in 2013 and plans to list on the Nasdaq under the symbol ALZH. ThinkEquity and H.C. Wainwright are the joint bookrunners on the deal. IPO timing was not announced.

Relevant Profile: ALZH

https://www.renaissancecapital.com/IPO-Center/News/59978/Alzheimers-biotech-Alzheon-sets-terms-for-$35-million-IPO