Experts agree icosapent ethyl a value at $4-$6

What these results show, however, is that at an average price of $4-$6 per day, “we think that the drug provides good value,” lead author William S. Weintraub, MD (MedStar Washington Hospital Center, Washington DC), told TCTMD. “It's very safe. We prevent a lot of cardiovascular events. There's a slight increase in atrial fibrillation, slight increase in minor bleeding, but overall prevention of cardiovascular events, cardiovascular death, stroke, and myocardial infarction is so strong that appropriate patients really should be treated with this.”

“It was gratifying to find out that if [this is] what people really pay, it provides very good value,” Weintraub said. “Now what do people really pay for this? [If it’s] somewhere between $4 and $6 a day, it's very little to [pay] because you're preventing so many events.”

Acknowledging that some insurance companies have made it tough for patients to both receive and afford icosapent ethyl in the past, he said those hurdles are likely to ease in the near future. “I think you're going to find that the drug is going to become widely available for appropriate patients,” he said.

Costs of Finding Patients?

In an accompanying editorial, Dariush Mozaffarian, MD, DrPH (Tufts University, Boston, MA), writes, “Based on the most data-driven ‘in-trial’ estimates, icosapent ethyl appears to be a cost-effective treatment for patients who have hypertriglyceridemia and either existing CVD or diabetes and another risk factor.”

However, he notes several caveats. First, because the cost-effectiveness data was based on patients treated in 11 countries, there is the possibility that the results may not be generalizable to the United States.

Even so, Rodriguez notes, “the study findings are most pertinent to the US where drug pricing and other healthcare costs have a lot of variation (and are typically higher than other countries).”

A US-based cost analysis has already been presented as an abstract, Weintraub said, but a manuscript is expected to be published within the year showing that the drug is “even more cost-effective in the United States,” he noted.

Mozaffarian also points out that the study did not include costs related to incremental physician visits, screening, or laboratory testing, which would “not be trivial,” nor would they be the same as the costs of regular patient care outside of a trial. “Based on the additional costs of a few extra clinic visits and blood tests over a 4.9-year period, the cost-effectiveness of [icosapent ethyl] treatment is likely overestimated,” he cautioned.

Weintraub, however, said this concern is “completely” off-base, since previous analyses have shown no incremental follow-up costs associated with icosapent ethyl. Additionally, “we think that patients are going to be found incidentally when they have routine lipid screening, . . . so there's no cost in finding the patients,” he said. “Our findings are actually conservative, and he was just wrong about that. We were quite disappointed to see that in the editorial.”

Rodriguez sided with Weintraub. “Preventing cardiovascular events saves a lot of money, so the incremental costs of outpatient clinician visits and follow-up laboratory, although not considered in this analysis, are likely acceptable,” she said.

Regardless, Mozaffarian said that “containing the drug cost of icosapent ethyl at or below $4 per day is critical to maintain its cost-effectiveness as a treatment. At a time when Congress is actively debating the need for payers to have greater ability to negotiate prescription drug prices, this sensitivity of cost-effectiveness to drug price has particular salience, especially when pharmaceutical spending per capita in the US is already two- to three-fold higher than in other high-income countries.”

Rodriguez agreed, saying: “I hope that drug manufacturers for cardiovascular therapies consider the importance of value–the balance between clinical benefit and cost.”

https://www.tctmd.com/news/icosapent-ethyl-cost-effective-compared-standard-care-reduce-it

It's quite amazing ...

... that a foreigner such as yourself has become a preeminent expert on the U.S. Justice system from following one case on an anonymous message board.

It really is quite a feet on your part.

Waz up, dawgs

Anything new around here?

NICE Technology Appraisal Committee will meet again on March 8th.

https://www.nice.org.uk/event/tacc-march-2022

Stifel on Vascepa in Canada


Keywood’s newest report comes with updated analysis on Canadian prescription data for Vascepa in January 2022, which indicated an annual net sales run rate of $26 million, producing ten per cent sequential growth and a 330 per cent year-over-year increase.

“Public reimbursement negotiations for Vascepa are still active, according to the pCPA website, where updates could be imminent,” Keywood said. “Achievement of public reimbursement could inflect the demand curve and represents approximately 60 per cent of the peak sales opportunity, where private reimbursement has already been achieved.”

On top of the sales component, Keywood also noted that the company began its partnership with Pfizer in late September, and appears to be contributing to increased demand at higher prescription volumes. All told, Keywood estimates there are just over 9,000 prescriptions for Vascepa patients in Canada, with a long way to go before fulfilling the potential for more than 100,000 prescriptions.

https://www.cantechletter.com/2022/02/patience-should-mean-a-big-reward-on-hls-therapeutics-says-stifel/

New Preston Mason publication

RATIONALE FOR DIFFERENT FORMULATIONS OF OMEGA-3 FATTY ACIDS LEADING TO DIFFERENCES IN RESIDUAL CARDIOVASCULAR RISK REDUCTION

Preston Mason
Samuel C.R. Sherratt
Robert H. Eckel

Published:February 10, 2022

Metabolism Journal - Clinical and Experimental


Cardiovascular outcome trials (CVOTs) have used omega-3 fatty acids (n3-FAs) to test if patients with residual risk and well-controlled LDL cholesterol levels benefit from specific lowering of plasma triglycerides (TG). Despite similar reductions in TG levels, the results of these trials have been highly inconsistent. This has led to interest in the role of n3-FA formulation, including the content of eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), as a basis for different clinical outcomes.

https://www.metabolismjournal.com/article/S0026-0495(22)00039-7/fulltext

French Committee makes reimbursement recommendations

Opinion in favor of reimbursement only in adult patients on treatment with a statin at the maximum tolerated dose, at very high cardiovascular risk due to established cardiovascular disease (secondary prevention) and presenting with moderately high hypertriglyceridemia (≥ 150 and < 500 mg/dL ).

Opinion against reimbursement in the other populations of the indication including patients with severe hypertriglyceridemia (≥ 500 mg/dL) and those with diabetes and at least one other cardiovascular risk factor (primary prevention).

https://www.investorvillage.com/smbd.asp?mb=2294&mn=8875&pt=msg&mid=22917240

NS - what's interesting about Reddy CEO presentation

Oh really. The judge in your antitrust lawsuit claiming Amarin bought up all the supply of the API might be interested in your words.




Let me help you out here Dr. Reddy. Would you care to acknowledge that your generic is not to be prescribed for cardiovascular risk reduction in this country. Did you just admit that the valid Amarin patents are not viewed as impediments to your market? Kinda sounded like you said you are entitled to the "innovator's" market.

Reddy CEO thinks entitled to entire Vascepa market

January 28th, 2022
Moderator: The next question is from the line of Sameer Baisiwala from Morgan Stanley. Please go ahead.

Sameer Baisiwala: Sir, the first question is on icosapent which is Vascepa in the US. Good job done on the market share gain. I think it's now stabilizing around 11-12% for the last few weeks. Have we reached the peak or what's the outlook over here? And is it the supply that is holding you back?

Erez Israeli: I think that the product is doing well. We are planning to continue to do well also in the next quarters to come. There is still a lot of market share to gain with this product as the innovator is still holding a nice market share. And in terms of supply, it is not constraining us at this stage.

Sameer Baisiwala: Then why is the market share in early double-digit and not much higher if supply is not holding you back? What's the roadblock?


Erez Israeli: The roadblock is the desire of customers to take the product from us.

Sameer Baisiwala: But that's a little counterintuitive because generic is lower priced. So, most of the time, customers are too happy to take generic products. Is anything different over here?

Erez Israeli: No, nothing different here.

There were 662 potential subjects in screening ...

... at time presentation was developed (likely early June). If 450 of these had moved to 'consented to study drug' between June 1st and June 18th, that would have taken the number to 1700, which may be getting close to "almost 2000", depending on the speaker. Median time to consent was 17 days, so it is possible there was a bunch of the 662 that got processed between June 1 and 18. Study recruitment very much dependent upon the efforts put forth by the staff. There could have been a push given the upcoming NIH presentation.

Looks like your best post yet

The likely strength of MITIGATE trial ...

... lies not in its Primary Outcomes or even its Secondary Outcomes, but rather in its tertiary outcome measures. If you put 2000+ people at cardiovascular risk on Vascepa and compare them on the below measures with a similar group not on Vascepa over a 6-month time frame, I believe it is likely that there will be significant differences among these measures. That would be a win for Vascepa independent of the viral URI data. And there was after all, 5 times as much MACE incidence already in the combined groups shown in June presentation as there was mod-severe viral URI (and twice as many hospitalization in combined groups for worsening heart failure hospitalizations as there was incidence of mod-severe viral URI).

Other Outcome Measures:

1. Percentage of participants who die due to any cause [ Time Frame: 0-12 months ]

2. Percentage of participants experiencing a major adverse cardiovascular event [ Time Frame: 0-12 months ]
Death due to any cause, hospitalization for myocardial infarction, or hospitalization for ischemic stroke

3. Percentage of participants experiencing an expanded major adverse cardiovascular event [ Time Frame: 0-12 months ]
Major adverse cardiovascular events, hospitalization for acute coronary syndrome, and coronary revascularization (i.e., percutaneous coronary intervention and/or coronary artery bypass graft)

4. Percentage of participants who are hospitalized for heart failure [ Time Frame: 0-12 months ]

5. Percentage of participants who are hospitalized for any reason [ Time Frame: 0-12 months ]

6. Percentage of participants who have an emergency department visit for any reason [ Time Frame: 0-12 months ]

But "enrollment" already at 35,200 in June

June 18th presentation: – 32,000 usual care + 3200 intervention= 35,200. Which is only 4400 from the 39,600 total ‘enrollment’ now seen on updated ClinTrials site. Of those, add 4000 to ‘usual care’ group and 400 to the intervention group. And even at 60% consenting of that 400, added to the ‘almost 2000’ the presenter stated, you still are going to get less than 2200 total IPE.

They had a low incidence of moderate-severe viral infections across IPE and usual care groups (combined, blinded), as seen in presentation, and that is why they were adding more IPE's and matched controls.

They did fail to update enrollment number on September 3rd when they did ClinTrial update, but that was probably just an oversight,

I have now. Thanks.

Probably more like 1550 in the IPE arm

Here is the way it works: 1:10 intervention to control allocation. The clinical trials site may have it wrong in suggesting that the intervention is IPE. The slides below suggest that intervention includes everybody they reach out to seeking to recruit. Slide 18 shows 3200 people in intervention but only 1244 in IPE. So the outreach is the intervention, which places them as potential matched subjects. Then, their cardio-doc has to sign off. Then they have to get ahold of the potential subject. Then the potential subject has to consent to being in the study. But consent at that point is likely oral to begin with. Then according to slide 21, there is another eligibility determination, and recruits can be slow to take the next step or may change their mind altogether about participating. The 1244 in slide 18 are the ones that initially said they would participate but not necessarily all of them decided to play. Indeed, slide 21 indicates that there was only 930 of these that had fully onboarded for the study when they made the presentation slides.

So no, they won’t have 3960 actual subjects taking IPE. They may have 3960 people they reached out to seeking to recruit and for each of whom they have 10 matched controls. That would be my guess. They may only have 1550 or so actually on IPE. The upside is that the declines-to-participate provide another comparison group for those that got the IPE – unlike the 39,600 controls, the study decliners at least were subject to an outreach (study invitation).

The reason that the enrollment got bumped from 16,500 to 39,600 is because they initially thought it would be easier than it was to get about 1600 subjects on IPE, and then had to increase the outreach group to almost 4000 in order to get 1500-1600 people on IPE.

All just surmisal.

https://dcricollab.dcri.duke.edu/sites/NIHKR/KR/GR-Slides-06-18-21.pdf#search=icosapent

I think that is unlikely

They already published design and rationale last year (May 2021)

https://pubmed.ncbi.nlm.nih.gov/33516752/


and posted presentation June 2021 concluding feasibility of such a trial

https://dcricollab.dcri.duke.edu/sites/NIHKR/KR/GR-Slides-06-18-21.pdf#search=icosapent

To simply be redundant to information already in public domain would make a mockery of "late-breaking"

NS - just that the COVID case analyses ...

... will be just a subset of the overall viral pathogen patients. It may be the non-COVID respiratory virus patients that show the greatest improvement from Vascepa.

Interesting presentation title

MITIGATE: A Pragmatic Randomized Trial of Icosapent Ethyl for High Cardiovascular Risk Adults in an Era of Coronavirus Disease 2019

Thanks iryokabu

Dead Man talking

You have posted multiple times that above are the criteria for the ‘adequate representation’ element of Rule 24(a)(2). They are not. They are the criteria if you are accepting that there is a rebuttable presumption that you have lost this element (i.e., there was adequate representation). They are the elements if you are going to argue that Amarin, with their expensive attorneys, didn’t provide adequate representation to EPADI during the trial. You’ll need to pack it in if you are conceding that this element weighs against you and that your only hope is rebutting that presumption.

Courts are split on the correct standard for establishing the first type of presumption-that of adequate representation from a party already present in the litigation. One group of courts uses a three-part spectrum test; the others use a same-ultimate-objective test. The three-part spectrum test first categorizes an absentee's interest as adverse, similar, or identical to parties already present in the suit. If a proposed intervenor has an identical interest to a party in the suit, then a presumption of adequate representation arises.

The same-ultimate-objective test creates a rebuttable presumption of adequate representation whenever an absentee shares the same ultimate objective with a party. This inquiry asks whether parties "seek to achieve the same objectives" as an existing party.

So, by making the argument you posted, you are either conceding that EPADI’s interest is either identical to Amarin or that you share the same ultimate objective of Amarin. EPADI’s interest/objective is having the judicial system recognize the grave error in legal reasoning committed at the District Court level, which may and should lead to patent validation. Amarin’s objective (and interest) is validation and non-infringement of its patents without resorting to pointing out the glaring judicial mistake made at the lower court level. Amarin’s and EPADI’s interests aligned until it was clear that Amarin was unwilling to take the most obvious post-judgment relief – getting the lower court to revisit their judicial reasoning that was based on misinterpreting basic statistical principles. EPADI is clearly not being adequately represented in this post-judgment effort and thus is not in a position to need any rebuttable presumption analysis.

It is time to make the arguments befitting the august forum you are entering rather than engaging in the hyperbole that the ‘red meat’ crowd on a message board is most incited by. Of course somebody still has to be thrown under the bus. You know you have to put up a succinct yet comprehensive oral argument. It can be done without a single mention of cropped tables or fraud (with no apologies to the red meaters):
----------------------------------------------------------------------
Esteemed panel, we are here today because a grievous mistake has been made at the lower court and we seek to have that mistake remedied.

But first, the Rule 24 motion. We are in the fairly rare position of seeking intervention post-judgment. Indeed, the required lack of ‘adequate representation’ of the Rule 24(a)(2) ‘intervention of right’ is to be viewed through the lens of the Rule 60 proceeding that we seek to have docketed. EPADI is here because Amarin affirmatively chose not to pursue this billion dollar judicial mistake, and certainly is not providing anything akin to ‘adequate representation’ in the proposed post-judgment proceeding by either the three-part spectrum test or the same-ultimate -objective test. We would have preferred Amarin pursue this mistake through a Rule 60 motion of their own, and they have decided not to do so; thus, while Amarin would undoubtedly like restoration of their patents, their interests in not pursuing the judicial mistake in a Rule 60 forum, obviously outweighs their interest in pursuing a statistical mistake in this case of such gravity that it has been written about in a respected medical journal. Clearly, Amarin and movant’s interest are not aligned. Other elements of 24(a)(2) include ‘an interest relating to the property or transaction that is subject of the proceeding, and shareholders of a company that has had its patent rights unceremoniously stripped away, certainly have an interest relating to Amarin’s intellectual property interests. The last element of 24(a)(2) asks if movant, EPADI, is so situated that disposing of this action without being heard may, and indeed does, impact EPADI’s interest, that of fair value of the shareholder’s investments in a company whose patents were mistakenly stripped away in a judicial proceeding.

I’m not going to spend time on permissive intervention because that ultimately is the judge’s call, and while we think we qualify under 24(b) as well, we will rely on our 24(a)(2) arguments.

The final section, of Rule 24, 24(c), requires Notice and Pleading. Movant certainly provided Notice to the other parties, and, as stipulated in our original submission to the District Court, relied upon the Amarin pleading, because at the time that Amarin originally submitted the pleading, its interests were perfectly aligned with EPADI in seeking to stop the infringement of valid patents.

The standing issue does not come in to the Rule 24 issue, but EPADI surely should have standing to bring the Rule 60 motion. Rule 60 (c) indicates Movant had up to one year to bring their motion and we did. Rule 60(b) states that a legal party may be relieved from a final judgement because of mistake. We are asking that Amarin ultimately be relieved of the faulty judgment that invalidated its patents. Rule 60(b) does not say that it cannot be a third-party movant that requests that relief, it states that a “legal party” may be relieved from a final judgement. EPADI clients have been stripped of millions of dollars by a judicial mistake. A ‘taking by government mistaking’ if you will. If EPADI doesn’t deserve the due process to have this issue heard after being stripped of great monetary sums by a judicial mistake, then I’m not sure who would. EPADI recognizes the possibility that the lower court, or this body, could acknowledge the grave mistake was made but through some other legal reasoning, decide to invalidate the Amarin patents. We find that scenario unlikely given the emphasis on the mistaken reasoning the Court appeared to put on the flawed patent analysis, but we recognize it is a possibility. Movant simply wants the Court to recognize the mistake and rethink its analysis.

Your honors, a grievous mistake was made at the District Court level, by a judge evidently not schooled in some very basic statistical principles. As pointed out in the medical journal article, it was a statistical mistake that is common but one that should never have been relied upon to invalidate valuable patents. Defendants abetted this mistake with their actions and misstatements, be they intentional or just negligent. But it is a mistake that should be corrected and if the company holding the patents is unwilling to call out this costly judicial mistake, for whatever their reasons may be, then it has fallen upon Movant to seek redress from this august panel.

Thank you your honors.

Seeking to "intervene" because of inadequate representation ...

... in a proceeding that never happened.

Inadequate representation not ineffective counsel nor legal malpractice

This is not a sixth amendment right to effective counsel case, which only applies to criminal cases. Adequate Representation for Rule 24 purposes is a construct that exists solely for Civil Rules of Federal Procedure and is very much a different standard than the 6th Amendment Constitutional guarantee.

Yet the argument is being put forth that because Amarin didn’t pursue a statistical argument that was published months after the District Court’s decision this is an example of inadequate representation.

The argument is also being put forth that because Amarin didn’t pursue fraud arguments based on a cropped table missing a legend that only added that the nonsignificant results clearly indicated in the table were calculated using a specific statistical test is an example of inadequate representation.

Finally, the argument is put forth that because Amarin didn’t pursue post-trial relief other than its appeals to the Federal Circuit and the Supreme Court that is an example of inadequate representation.

The above are all considered legal strategies and have little to nothing to do with the Civil Rule construct of adequate representation. And adequate representation refers to the time period and interests during the case-in-chief, not during some post-judgment period, so we can throw the “failure to file a Rule 60 motion” out as grounds altogether.

The case-in-chief was “is there a patent infringement and are the patents valid”? The only issue for this required prong of Rule 24 was whether there was adequate representation of EPADI’s interests DURING the case-in-chief. You can’t say “Amarin lost the case and then didn’t pursue the post-trial relief I favored so that shows there was inadequate representation during the already-concluded case.” You’d need a time machine for that. There is perfect overlap between Amarin’s interests and EPADI’s interests, i.e. valid, non-infringed patents. The fact that Amarin deployed attorneys charging hundreds of dollars an hour to fight for Amarin patents means that EPADI’s interests as shareholders in the Company were well represented. Period.

Disagreeing with a legal strategy does not mean a third party’s interests were not adequately represented. If that was the case then EPADI should have added Amarin’s choice of venue for the trial to their list of grounds demonstrating inadequate representation.

EPADI is basically arguing legal malpractice rather than “adequate representation.” But, even dressed up in a malpractice cloak, this effort would fail. A legal malpractice case seeks to show that the lawyer’s representation caused their client not to prevail in their case and the incompetent representation by the lawyer caused damages to the client. Tough to prove in this case given the the Patent Office originally refused to grant patents because of obviousness.

A common example of legal malpractice is a lawyer missing an important filing deadline that caused their client’s case to get dismissed. Critically, in order to recover financial compensation, it must be demonstrated that the attorney made a mistake and if the mistake never occurred, the client would have prevailed in their case.

So, even under a “legal malpractice” standard, which the Appeals Court is not accepting, it would be impossible to definitively prove that “but for” the missing table legend or a comment by opposing counsel that did not get rebutted, there would have been a different outcome in the trial.

EPADI may not like the results of the court case, but getting the Appeals Court to find there was not adequate representation of EPADI's interests DURING TRIAL will not happen.

Chinese Expert Consensus recommends statin+ for elderly

https://www.investorvillage.com/smbd.asp?mb=2294&mn=8844&pt=msg&mid=22846057

Thanks NS; Kaiser should update website.

But when does enrollment begin?

https://kpstudysearch.kaiser.org/vd.aspx?re=1172&hs=1597940

"Poisonous troll" breaks AHA embargo.

https://www.investorvillage.com/uploads/87669/files/AHA-scientific-statement.pdf

"In patients with diabetes and ASCVD or patients with diabetes at high risk for ASCVD with serum triglycerides of 135 to 500 mg/dL despite maximally tolerated statin, and addressing contributory factors including lifestyle modification prescription icosapent ethyl at a dose of 4 g/d, as well, should be considered given the 30% additional cardiovascular risk reduction in the REDUCE-IT trial (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial). Of note, the median baseline LDL-C in this trial was 75 mg/dL, and 29% of the study population had diabetes."

I couldn't agree less.

Why didn't you use the modicum of sense needed to translate on your own with the link that was provided so you didn't put yourself in the position of looking like someone who is more concerned with something other than accurate information. If you had translated and come up with something different, then we might have have had something to discuss. But stick with getting answers from your Nordic connection, whoever he/she may be, who is obviously a fount of misinformation.

I provided link to do own translation

Eton=Etten=Eddingpharm = Chinese language not easily translatable.




Edding sells two Lilly drugs.

-------------------------------------------
Bottom line, Edding has had difficulty attracting new investors (as I was posting last month when many were stating the high likelihood of Vascepa being approved in China by end of 2021).

Not all roses for Edding

Eton Pharmaceutical’s Hong Kong Stocks "Three Enters the Palace"
January 02, 2022 18:08:23


Nowadays, the capital market is more demanding on the assessment of listed companies. In other words, it is much more difficult to get money from investors than in the primary market. Therefore, it is still unknown whether the "Three Enters" of Eton Pharmaceuticals will succeed in the end.

In the past 2021, although many companies succumbed on the way to go public and then fought again, there are not many companies with the spirit of "three-minded", and Eton Pharmaceutical is one of them.

On December 15, 2021, the Hong Kong Stock Exchange reported that Eton Pharmaceutical Group Co., Ltd. (hereinafter referred to as Eton Pharmaceutical) submitted a listing application to the Hong Kong Stock Exchange.

Prior to this, on September 23, 2020 and March 29, 2021, Eton Pharmaceutical submitted listing applications to the Hong Kong Stock Exchange, and passed the hearing on June 25, 2021, but no subsequent IPOs took place. The prospectus lost its validity in September.

The prospectus submitted by Eton Pharmaceutical this time has updated relevant data for 2021 and explained some topics that investors are concerned about.

According to the prospectus, Yiteng Pharmaceutical's 2017, 2018, 2019, and 2020 revenues will be 1.787 billion yuan, 1.478 billion yuan, 1.874 billion yuan, and 1.768 billion yuan; gross profit will be 604 million yuan, 538 million yuan, and 8.6 billion yuan respectively. 100 million yuan, 1.063 billion yuan.

In addition, Yiteng Pharmaceutical's annual profits for 2017, 2018, 2019, and 2020 were -38.54 million, -215 million, 173 million, and 86.94 million respectively; the profit rates for the year were -2.2% and -14.6%, respectively. , 9.2%, 4.9%. Yiteng Pharmaceutical's 2020 annual profit dropped by nearly 50% compared with the same period of the previous year.

In the first half of 2021, Yiteng Pharmaceutical's revenue was 853 million yuan, with a profit of 26.94 million yuan; the revenue for the same period in 2020 was 595 million yuan, and the loss during the period was 43.61 million yuan.

It is such a pharmaceutical company that was originally just an ordinary process of listing and financing, but because of the "three times of entering and leaving the Hong Kong Stock Exchange" experience, many media and investors are very curious.

"Bullet Finance" found that if you carefully analyze the business and corresponding management model of Eton Pharmaceuticals, you will find that this company is not favored by the capital market. There are indeed reasons for this.

Starting from an agency, transforming through acquisitions

According to the information on the official website of Eton Pharmaceuticals, the company was founded in 2001, focusing on the three major therapeutic areas of anti-infection, cardiovascular disease and respiratory system. Famous leading anti-infective drugs.

However, what surprised investors and the media was that until October 2019, these two drugs belonged to the internationally renowned Eli Lilly Pharmaceuticals Group. At that time, Eton Pharmaceuticals was only the general agent of Eli Lilly in China. In January 2017, the two drugs were promoted and sold in China.

Strictly speaking, Eton Pharma is a CSO company in the pharmaceutical field, which is also a so-called outsourcing company for drug sales. Due to the lack of understanding of the Chinese market by foreign pharmaceutical companies, they will choose local pharmaceutical CSOs for marketing when opening up the market, which has become a domestic CSO company.

At that time, Yiteng Pharmaceutical gradually became a domestic CSO giant by virtue of its cooperation with foreign pharmaceutical companies. Therefore, it was favored by capital and received investment from well-known investors such as Sequoia Capital and Aobo Capital.
Following the implementation of the "two-invoice system" and "VAT reform" in China, the pharmaceutical CSO industry has been hit, and Eton Pharmaceuticals is also forced to start its transformation.

In October 2019, Eton Pharmaceuticals acquired the qualifications of Eli Lilly and Company to produce and sell antibiotic products Xikerao and Wencheng in mainland China through the acquisition, as well as the Xikerao production plant in Suzhou; in 2020, Eton Pharmaceuticals will GlaxoSmithKline acquired the core respiratory system product FPN; in addition, Eton Pharmaceuticals also authorized the introduction of three drugs, Vascepa, Mulpleta and EDP 125.

Stable and credible, that is, vancomycin hydrochloride for injection. This drug is used to treat methicillin-resistant Staphylococcus aureus infections. It is a powerful drug-resistant bacteria. It is mostly found in ICUs and other intensive isolation wards of hospitals. It is usually associated with invasive procedures or equipment (such as surgery, intravenous catheters or Artificial joints).

Methicillin-resistant Staphylococcus aureus infection is very common in severe hospital areas, especially orthopedic or surgical wards. Therefore, anti-infective treatment of this unique bacteria is the fastest growing segment of the antimicrobial drug market Market, and Wenxin is the market leader in the treatment of this infection.

According to the Frost & Sullivan report disclosed in the prospectus of Eton Pharmaceuticals, based on the sales revenue in 2020, it is believed that the market share of this kind of pathogen infection drugs is 27.3%.
Xikerao is a cefaclor drug, which is generally used for the treatment of respiratory tract infections and urinary tract infections in adults and children. In 2020, the market share of Xikerao is calculated based on the sales revenue in the general infection treatment market in China. It is 25.9%.

FPN is the latest generation of hormone nebulizer for the treatment of asthma. It was launched in China in 2017 and is currently the most effective drug for controlling airway inflammation. Eton Pharmaceuticals started exclusive sales of FPN in November 2019, and acquired this drug from GSK in May 2020.

According to the Frost & Sullivan report, in addition to FPN, there are only two ICS (inhaled corticosteroids) nebulizers currently sold in China. FPN is the only non-fake version that is included in the National Medical Insurance Catalog.

In addition, the above report also pointed out that the anti-infective field that Eton Medicine is good at has become the fastest growing therapeutic field in China. In 2020, anti-infection is the fourth largest therapeutic field in China, with a market size of RMB 174.2 billion, accounting for 12.0% of the entire Chinese pharmaceutical market.

Today, Eton Pharmaceuticals is a comprehensive pharmaceutical company that has established a high-quality product portfolio containing six core products, including three commercialized original brand products and three innovative new drugs under development. However, all of its core commercial products (ie, Xikerao, Wencheng and FPN) are original brand-name drugs without patent protection.

In the first half of 2021, Xikerao and Wentong generated revenues of 273 million yuan and 324 million yuan respectively, accounting for about 70% of Yiteng Pharmaceutical's revenue in the first half of 2021.

However, since the patent protection of these two drugs has expired, this has become an important place for investors to have doubts about the future development of Eton Pharmaceuticals.

What's worse, the current research and development of Eton Pharmaceuticals' new products is lagging behind. Currently, the six drug patents that are core products are all purchased, and no self-developed drugs are being sold.

Rely on foundry and sales system

Unlike major manufacturers such as Harbin Pharmaceutical Group and Baiyunshan Pharmaceutical, Eton Pharmaceuticals has a weak ability to produce medicines. Most of its medicines are produced and packaged by third parties, and then sold by themselves.

This is the so-called CMO asset-light operation model. (Editor's note: The full name of CMO is Contract Manufacture Organization, that is, "Global Biopharmaceutical Contract Manufacturing")
In the prospectus, Eton Pharmaceuticals explained this, and included the changes and potential impacts of the manufacturer into the risk items.

The prospectus shows that both Wencheng and FPN are produced by CMO's foundry companies for the full version. Among them, FPN also imports part of the raw materials from overseas and then delivers them to the final foundry for production.

Only Hitlau was produced by Eton Pharmaceuticals itself. The reason was that when Hitlau was bought out from Eli Lilly, the condition given by Eli Lilly was to take over the factory in China, which is still in operation. None of the management team has changed.

"According to the information we understand, the people of Eton Pharma didn't think about taking over the operation of the factory, but it found that the yield rate dropped too much after it sent someone to take over, so it switched back to the original management team. The CMO model is in It is not common in the medical field, and the practice of Eton Pharmaceuticals does appear to be quite risky." Liu Yanru, a well-known Hong Kong investment bank analyst, told Bullet Finance.

However, objectively speaking, compared with other pharmaceutical groups, Eton Pharmaceutical's marketing capabilities are quite good. According to the prospectus of Eton Pharmaceuticals, its sales and marketing network has more than 1,000 sales representatives, including more than 22,000 hospitals in 30 provinces in China, enabling the company to obtain sustainable sales and cash inflows.

In Liu Yanru's view, this is probably the important basis for Eton Pharmaceuticals to "break the Hong Kong stock market three times." "This is actually similar to many new consumer Internet brands. They are all empowered by brands. Merchants are only responsible for designing products, and third parties help to produce them, and then sell them through a strong marketing network." Liu Yanru said.

However, Liu Yanru believes that such companies will likely show certain disadvantages in the financial report data. "Generally, companies with strong sales capabilities will account for a very high proportion of sales expenses, and the same is true for Eton Pharmaceuticals."
Data from the prospectus shows that in 2020, Etton Pharmaceutical's marketing expenses will exceed 173 million yuan, and in the first half of 2021, it will set a record of more than 224 million yuan.

Due to high sales expenses, the company has been losing money with annual revenue of more than one billion yuan. In 2017 and 2018, the company lost 38.53 million yuan and 215 million yuan respectively, but it turned losses into profits in 2019 with a profit of 172 million yuan.
It is worth mentioning that many multinational pharmaceutical companies are now stripping off core assets and selling expired patent drug businesses to reduce cost pressure. In this context, still relying on the original pharmaceuticals with expired patents obtained from overseas to manufacture them in China, and then sell them under their own brands, how sustainable a business model such as Eton Pharmaceuticals really makes many investors feel disturbed.

The key is that under this model, Yiteng Pharmaceutical's cash flow has undergone some unsatisfactory changes.

The prospectus shows that as of June 30, 2021, Etton Pharmaceutical’s cash and cash equivalents were only 233 million yuan, and the accounts receivable were 594 million yuan, while short-term payables and bills were 101 million yuan, and other payables were 278 million yuan. Short-term loans of 718 million yuan.

It can be seen that its cash is far from being able to repay the short-term and medium-term costs of current liabilities, and even if it is guaranteed that the receivables are fully recovered, it cannot be offset against the books. What's more, it is impossible to recover all the receivables, and about 10% of them will generally be accrued for losses.


"When such financial reports are placed on the desk of any investment bank, it is impossible for investment banks to be interested in the stocks of such companies." Liu Yanru told Bullet Finance. She believes that the financial pressure on this company is too great. , Investors will feel the risk, "the decision-making will be more cautious."

Split R&D into the market

It stands to reason that pharmaceutical companies should focus on research and development, and even large-scale listed pharmaceutical companies lose money due to huge R&D investment.

Eton Pharmaceuticals is completely different from the model of these pharmaceutical companies. Its losses are caused by marketing expenses exceeding 30% of its income level, and the cash flow problem is also related to excessive receivables.

In terms of research and development expenses, this large pharmaceutical company with annual sales revenue of about 1.8 billion yuan, the corresponding expenditures shown in the financial report can be described as "a pitiful little."

In 2020 and the first half of 2021, Yiteng Pharmaceutical’s sales expense ratios were 24.2% and 26.3%, respectively, while the R&D expense ratios during the same period were only 3.4% and 5.4%, and the company's R&D relied on third-party pharmaceutical R&D companies.

In the first half of 2021, Eton Pharma’s marketing expenses exceeded 240 million yuan. While setting a record, it only spent less than 45 million yuan in research and development expenses.

In a sense, CRO (the full name of CRO is Contract Research Organization, that is, contract research organization) has become the "killer" of Eton Pharmaceuticals in response to regulatory requirements that pharmaceutical companies must invest in research and development. By entrusting third-party R&D, they can also control the cost of R&D investment, and reduce the cost of final drug production by requiring tripartite research institutions to provide the lowest-cost drug combination.

However, it cannot be said that Eton Pharmaceuticals has no research and development at all. Ni Xin was the founder of Eton International and started as a pharmaceutical sales company. In 2010, he also founded Eton Medicine's "brother unit" Eton Jingang.

For a long period of time, Eton King Ang only appeared as a unit of oncology drug R&D application of Eton Pharmaceutical R&D department, and the real scientific research expenditure and team fell under the name of Eton Pharmaceutical.

Beginning in 2019 when it was preparing to hit the Hong Kong stock market, Eton Pharmaceuticals has packaged the development of oncology drugs, which originally accounted for the bulk of scientific research expenses, into Eton King Ang. The reason may be to reduce the risk of loss, or to divest businesses that have not yet seen the ability to make money.


Eton King Ang is a bio-innovative drug company. There is no successful drug research and development, but it has 12 research projects, including type 1 HDAC selective inhibitor EOC103 (Entinolate), VEGFR inhibitor EOC315 (Terrati Ni), etc., covering multiple indications such as breast cancer and gastric cancer.

It is worth mentioning that while Eton Pharmaceutical will restart its impact on the Hong Kong stock market in 2020, it has also pushed Eton Jingang to the Science and Technology Innovation Board. However, due to unclear business and high R&D risks, the Science and Technology Innovation Board eventually terminated the company's declaration.

"This is already the third time that Eton Pharma has hit Hong Kong stock IPOs. In June this year, it has passed the Hong Kong Stock Exchange's hearing and can proceed to the next stage of raising funds from the capital market and negotiating with investment banks. However, Eton Pharma has Choosing to terminate the listing process." Lin Xi, a well-known Hong Kong analyst, told Bullet Finance that this is actually the result of Eton Pharmaceutical's judgment on the market.

In his view, on the one hand, the financial report of Eton Pharmaceuticals shows that there will be a big problem with the cash flow. On the other hand, there are almost no new products. The products it sells are all based on patents bought from abroad, and these patents have expired. Exclusive enjoyment, "Such an enterprise is not very attractive to investors in the capital market, and the risk is too high."

"Edden Pharmaceuticals is also aware of this. It is now reopening its IPO application and has added a lot of content describing its business prospects." Lin Xi added that he is still not optimistic about the listing process of Eton Pharmaceuticals, thinking that it is now The state of development of medicine is still far from the bottom line in the minds of investors.

"They have now split the research and development of oncology drugs. In fact, this area is attractive to many investors, because those drugs must be patented and sold exclusively after the listing of Eton Pharmaceuticals." Lin Xi said.

Of course, in his opinion, it is understandable for Eton Pharmaceuticals to dismantle this part. After all, this part of investment is too large. "If this part is added, the originally unsightly financial report will appear even more unsightly."

He believes that the key is how investors will think about it in the future. "There is a high probability that it will pass the hearing of the Hong Kong Stock Exchange. This depends on the development of the securities market in Hong Kong after the hearing. It may succeed in listing, otherwise it is dangerous."

In addition, he also speculated that Eton Pharmaceuticals is now hurriedly listing in Hong Kong, and it is a "three-in-one", which is likely to be related to short-term liquidity tensions.

Nowadays, the capital market is more demanding on the assessment of listed companies. In other words, it is much more difficult to get money from investors than in the primary market. Therefore, it is still unknown whether the "Three Enters" of Eton Pharmaceuticals will succeed in the end. (Source: Bullet Finance)

https://www.hstong.com/news/detail/22010211290167632

Registration closes 4 January for UK meeting

https://www.nice.org.uk/event/tacc-january-2022

I think Edding will want to try ...

... selling Vascepa on their own in China

It looks like Edding has accrued substantial debt (current investors including Sequoia Capital, Orbimed Capital, Domain, Double Prestige, Forebright, Shanghai Pudong Development Bank, Credit Suisse, China Huarong Asset Management's Ace City, Abax Global Capital, etc.) and so Pfizer might want to wait awhile before making an investment behind a list of others.

Of course another wild card in all this is future relations between China and the West. That could tend to make some potential investors nervous. I set up an account six months ago so I could trade on the HKEX. Trump/Biden have prohibited U.S. persons from transacting in the publicly traded securities of Chinese companies that the Department of Defense has identified as CCMCs (Communist Chinese Military Companies), so you never know how far this will go. And, Hong Kong becomes more tightly in the grip of China with each passing day, and that also makes me less eager to invest in a company on the HKEX.

The two are inextricably tied

NMPA approval without launch funds doesn't do Edding any good (nor the Chinese people any good). I'm suggesting that the public offering is being coordinated with an eye toward when the NMPA and Hong Kong FDA approvals will actually occur. The IPO doesn't directly impact NMPA approval but will be a forerunner to NMPA approval (I'd bet Jasberg's life on it). Plus, China government officials will likely be investors in Edding and will want to see as short of time frame as possible between drug approval and drug launch.

Edding wants to join the bigs ...

... but does not have the private investors to do that (one guy controls 43% of the company). They are a Chinese company, but Communist China doesn't have a Stock Market on which they can go public. China does allow stock exchanges in their special economic zones, such as Hong Kong and Shanghai. So, in order for Edding to get the launch money they want, for both Vascepa and Mulpleta, they need to get investors through, first a roadshow, then a listing on a public stock exchange. Hence the IPO in Hong Kong.

Probably no China approval ...

... before Edding IPO is complete and Edding listed on HKEX. Government in cahoots with pharmaceutical companies and Edding needs to raise money before launch. Bad news is Hong Kong IPOs moving very slowly this year. Good news is that after an initial false start, Edding just re-submitted.
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On December 17, Capital State learned that Eton Pharmaceuticals submitted a prospectus to the Hong Kong Stock Exchange and planned to be listed on the Hong Kong Main Board IPO. The company previously submitted the prospectus twice on September 23, 2020 and March 29, 2021, and then passed the hearing of the Hong Kong Stock Exchange on June 25, 2021. The prospectus was invalidated after the IPO was not initiated.

https://www.sohu.com/a/509308618_223785
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Fat cats in the mainland can just slip over to Hainan to get their Vascepa. It recently got easier to get prescriptions there.

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15:08, November 25, 2021 Source: Nanhai Net

Xin Hainan Client, Nanhai Net, Nanguo Metropolis Daily News on November 24 (Reporter Su Guizu) The reporter learned from the Lecheng Pioneer District Administration that the Hainan Provincial Drug Administration recently approved the approval of the Boao Lecheng Pioneer District. Life Care Center, licensed clinical application for batch application of 300 bottles (120 tablets/bottle) of imported drug Icosapent ethyl (VASCEPA®) urgently needed.

According to the spirit of the relevant documents, the clinically urgently needed imported drugs (excluding vaccines) and medical devices to be used in the Lecheng Pilot Zone can be stored in batches in the bonded drug warehouses in the Lecheng Pilot Zone before approval. After the medical institution obtains the approval for the use of urgently needed drugs from the drug regulatory department, the imported drugs urgently needed for clinical use can be cleared out of the warehouse in batches and distributed to the medical institution for use.

The 300 bottles approved this time, totaling 36,000 Icosapent ethyl (VASCEPA®) licensed drugs, are the results of institutional innovation by the relevant departments of Hainan Province to further simplify the approval process of clinically urgently needed imported drugs and optimize the approval model.

After the batch application of medical institutions is approved by the Hainan Provincial Food and Drug Administration, doctors can prescribe urgently needed clinically imported drugs for patients to use according to the needs of patients and under standardized use standards.

This benefit has also further optimized the "Bring medicine and leave the park" policy in the Lecheng Pioneer Zone. After the patient is discharged from the hospital with medicines, there is no need to record real-time video and upload it to the imported medical equipment traceability system of Lecheng Pioneer District every time a medicine is taken. It only needs to feed back the first, intermediate and last medication records to the medical institution, which truly simplifies the medication process for patients with chronic diseases. , Bring convenience for the long-term medication of patients with chronic diseases.

Yue Hongwen, director of the Boao Yiling Cardiovascular and Metabolism Medicine Center, said that the batch approval policy has brought great convenience to patients and medical institutions. Medical institutions can use it for patients according to clinical needs, and are no longer subject to the restriction of one person, one medicine. The efficiency will be greatly improved, and it will truly realize the benefits of letting patients wait for medicines.

http://www.hi.chinanews.com.cn/hnnew/2021-11-25/613568.html

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If you mean Curfman, et al

.. then it is very relevant. I've said before, if the filing had been about "mistake" alone, rather than fraud, clean hands, fraud on the court, etc. it would still have been an uphill battle ... but fought from the high ground rather than from the muck.

I find it perfectly plausible ...

... that you yourself would have a difficult time reading a table not knowing that the statistical differences, clearly delineated as being significant or NS, were determined using Student's t tables. I would, however, hesitate to say that your inability applies to all others.

But please Mr. EPADI attorney ...

... can you just point to the two tables on the screen for the Court and show us the much ballyhooed fraud that was repeatedly mentioned in your filing. It should be an easy matter given the seriousness of the charge and how you have placed the cropped table as the crux of your allegations.

Fake news. You ever even looked at Table3?

First, there is no placebo group. Second, all the NS's were left intact in the "cropped" table.


One of my bigger problems with EPADI attorney is he applauds this type of misinformation rather than correcting it. Because to correct it would be to admit what information really was cropped, which then prompts the need to go into contortions about how this missing non-material information represents a fraud. When asked directly, HK took the tact of answering with 600 words, none of which directly addressed the issue. If people don't think that HIKMA/Reddy are salivating over the chance to put the cropped and non-cropped versions of Table 3 on a Powerpoint slide next to each other in Court, then they don't understand how this works. And that's when all the air goes out of the fraud balloon that ziploc and others continue to inflate with flatulence.

https://www.investorvillage.com/uploads/87669/files/Table3-cropped-notcropped-highlighted.pdf

ggwpq - Amarin didn't have to go thru process...

... for reimbursement in Germany. Amarin got to set its own price for the first year (and it is reimbursable).

NS - I don't know when Denmark will grant reimbursement but I would think it shouldn't be too long. They may not beat France who I anticipate within a month or so.

I'll volunteer being good samaritan that I am.

Vazkepa is for sale in Denmark and England (and maybe Norway and others). If you have private insurance or want to pay cash (or kroners) then it is available. You'll know when it is fully reimbursable in Denmark when the little black ball shows up on the website below. You can put in some already-marketed drug (e.g., gabamed) and see what it looks like.

https://medicinpriser.dk/default.aspx?lng=2

French Transparency Committee to adopt Vazkepa opinion 12/15/21

https://www.investorvillage.com/uploads/87669/files/FrenchMeeting-12-15-21.pdf


These three aspects of a Committee Opinion represent its main conclusions, and answer the five questions posed by the decision-makers, which are:

» Should this medicinal product be reimbursed by French national insurance, in hospitals or in community practice, yes or no?

» What level of contribution should be made by the person insured?

» What is its added clinical value, i.e. the improvement in treatment (or diagnosis) contributed by the medicinal product compared with existing products, in the context of current optimal care?

» What is the size of the population for which reimbursement is justified or in which the medicinal product represents added value?

» What impact (or even benefit) does this medicinal product have on public health?

These conclusions are aimed at a number of stakeholders:

» Decision-makers: CEPS which sets the price; the Chief Executive of UNCAM9 which sets the level of reimbursement; the Minister of Health, who takes the final decision on reimbursement.

» Stakeholders involved in the proper use of the medicinal product: the company that markets the product; health professionals, particularly the doctors who prescribe it and the pharmacists who dispense it; the patients and citizens (for preventive therapies) who use it.

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In France marketing authorization for drugs can be obtained at the national or European level. The French regulatory agency for drugs is the National Agency for the Safety of Medicine and Health Products (ANSM).

There are 3 key bodies involved in the process of approving a product and agreeing pricing and reimbursement levels:

The Transparency Committee (Commission de la Transparence, or CT)

The Economic Committee on Healthcare Products (Comité Economique des
Produits de Santé, or CEPS)

The National Healthcare Insurances (Union Nationale des Caisses d’Assurance Maladie, or UNCAM)


Simply put:

The CT is in charge of assessing the medical benefit (known as SMR) and the improvement of medical benefit (known as ASMR) of a new medicine for which a pharmaceutical company submits a request for inclusion in the reimbursable drugs formulary.

Drug price setting is established by CEPS after negotiation with the drug company. The ASMR is one of the key items taken into account during price setting.

The reimbursement rate is fixed by a decision from UNCAM, primarily based on SMR. The HAS (Haute Autorité de Santé) then makes the final decision regarding whether or not the drug will be registered on the list of reimbursable medicines. This registration is valid for 5 years. At the end of this period or at any time when significant new information becomes available, the CT reevaluates the SMR and ASMR levels.


It is important to note that the ASMR is mainly driven by the effect size of the benefit of the drug. Although the effect size concept is a well-defined and standardized measure of the benefit over a comparator, in France, the effect size is considered by the CT as a very subjective endpoint that relies on the expert assessment of the CT members. The lack of decision analysis framework leaves some unpredictability.


The Transparency Commission considers the level of innovation the drug brings to the market, as well as how important it is to the health of French citizens. It determines the drug’s improvement of medical benefit or amelioration du service medical rendu (ASMR) compared to the current standard of care, and assigns a rating from 1 to 5:

ASMR V: no improvement

ASMR IV: minor improvement

ASMR III: moderate improvement

ASMR II: important improvement

ASMR I: major improvement. This is reserved for an extremely few drugs that have demonstrated effect on mortality in a severe disease.

The ASMR answers the question: does the drug improve patients’ clinical situation as compared to existing therapies? Consequences of ASMR rating and level of price are as follows:

ASMR V – the drug can be listed only if the costs are less than the comparators for cost savings to the French National Health Insurance (NHI). Discounted pricing for the new drug is typical.

ASMR IV: the target population for the new drug is relevant. If the new drug targets the same population as the comparator drug, then a parity price is best possible outcome. Price can be higher than a comparator if the new drug has better effect in a more restricted population.

ASMR I, II or III: Faster access (price notification instead of negotiation) and price consistency with rest of Europe. However, it is increasingly rare to secure ASMR I – III ratings.

The Transparency Commission also determines the product’s medical benefit or service medical rendu (SMR). The SMR answers the question: should the drug be reimbursed? Is the drug clinically differentiated (interesting)? The SMR considers five criteria:

Severity of the disease to be treated and its impact on morbidity and mortality

Clinical efficacy/effectiveness and safety of the medicine

Aim of the drug: preventive, symptomatic or curative

Therapeutic alternatives? Positioning in treatment strategy for the disease, indication or condition?

Public health considerations – burden of disease, health impact at the community level, transposability of clinical trial results etc.

The CT assigns each drug a rating of 1 to 5 corresponding to its medical benefit, referred to as the “medical service rendered” (service médical rendu, or SMR), which determines the percentage of price that NHI reimburses. The CT considers the gravity of the problem, the medication’s effects, and its public health impact. NHI reimburses 100 percent of medicines for afflictions that lead to death if untreated and for grave, long-term illnesses, such as diabetes. It reimburses other medications as follows:

65 percent for drugs awarded a major or important SMR
30 percent for drugs with a moderate SMR
15 percent for low SMR drugs
0 percent for drugs receiving an insufficient SMR.


The ASMR and SMR ratings described above, are determined concurrently. Once they are determined, the manufacturer enters negotiations with The Comité Economique des Produits de Santé (CEPS) to establish the reimbursement price and rate for innovative ambulatory (retail) drugs. The ASMR level determined by the TC and the expected annual sales volume are key considerations for the CEPS when establishing price.


For each new medication, the CEPS negotiates a five-year contract with the manufacturer that specifies the price and anticipated sales volume. This discourages the marketing of drugs for indications that are approved by the European Medicines Agency (EMA) but not reimbursed by health insurance, as well as the marketing of drugs for off-label uses. The agreement on price and anticipated sales volume constitutes a cap on revenue. When sales exceed the contract cap, manufacturers pay rebates of between 50 percent and 80 percent.

The CEPS has the option of employing a performance contract under which the manufacturer refunds a portion of the price if the drug does not produce specified clinical results.

Negotiated Discounts and Market Competition

Once a list price has been set based on the value of the drug, CEPS negotiates a confidential discount (typically 10% to 30%), which is paid as a rebate to the Central Agency for Social Security Organizations.14 This is similar to negotiations between manufacturers and insurers in other European Union (E.U.) nations (see box below). Hospitals in France can sometimes obtain additional discounts through a competitive bidding process and price negotiations when competing drugs exist.

Impact on Innovation

Critics often contend that capping prices will eliminate or slow access to new medicines. It hasn’t in France, where manufacturers sell the full spectrum of innovative drugs available in the E.U. In fact, France explicitly rewards innovation by requiring the CEPS to pay more for new products that offer an important therapeutic improvement and to set prices that are consistent with reference prices in other E.U. countries. This system provides incentive to bring drugs to market that offer significant therapeutic improvement, rather than “me too” drugs.

However, industry critics note that the process of evaluating the added benefit of new drugs and reaching a price agreement is slower in France than in some other European countries. A European Commission directive set a goal for completing such work in 180 days. In 2017 it took France 168 days to complete this process, with another 45 days until the price was published in the official journal.2

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Marking the conclusion of intense negotiations between Leem and CEPS, this framework agreement introduces profound revisions to some of the rules governing the setting and regulation of prices for medicines with the aim of achieving five key goals: shortening lead times, promoting patient access to innovation, boosting investment and exports, facilitating supplies of medicines addressing public health needs, and improving transparency, in accordance with the engagement letter sent to the Chairman of the Economic Committee on 19 February 2021 by the ministers supervising the CEPS. Provisions include:

Fast-track Access within 15 days for medicines given an ASMR 1-3 rating dominant in terms of efficiency, medicines given an ASMR 4 rating dominant in terms of efficiency and saving, and medicines given an ASMR 5 rating priced below the comparator

Price stability and predictability - The 5-year stability period for the Europe-wide price of medicines given an ASMR 1-3 rating with a valid health economic assessment covers both the face value cost and the net price

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Expected NICE publication date still 3/23/22.

https://www.nice.org.uk/guidance/indevelopment/gid-ta10736