In late 2018, medical cannabis was downgraded from Schedule 1 to Schedule 2 (medically allowed) in the Misuse of Drug Regulations in the UK. There has been a lot of buzz in the news around this subject and there appears to be a patent grab underway but I am covering in this article today if it is feasible.
The two main cannabinoids of interest are cannabidiol (CBD) and tetrahydrocannabionol (THC). CBD lacks the psychotropic effect of THC. It is not considered a controlled substance (regulated by the government) in its pure from but it is said to be very hard to purify and products containing CBD are presumed to also contain other cannabinoids. However it is still possible for such CBD and other incidental cannabinoid substances to be in the medically allowed schedule of the controlled substances legislation.
There still remains a wide perception in the medical community regarding the benefits against potential dis-benefits of many non-medically approved cannabinoid products. There are a multitude of non-regulated products on the market, including vitamins, minerals, oils and herbal extracts. There is only one medically approved product in the UK called Sativex, a treatment for spasticity in MS sufferers which contains both CBD and THC.
Since the cannabis plant has been used for thousands of years, there is a popular opinion that it cannot be patented. This is not necessarily true and there has not been much prior experience in this field as it would have been considered illegal.
As previously mentioned, there are a multitude of non-medically approved products on the market with varying claims to their content, it is very hard to quantify their claims and ensure batch quality. Both CBD and THC are hard to purify, therefore accordingly processes to isolate, extract and purify cannabinoids may well be patentable as well as any stable forms achieved. Claims could be made for patents on the adaption of current delivery methods such as nebulization and formulation for vaping but there is a high chance, they would not be considered inventive enough.
There have been calls by many organizations to the Health and Social Care Committee calling for clinical trials to substantiate the claims. However, constructing the usual double-blind trials will pose an issue as patients will know they are not receiving the placebo as they will experience the ‘high’ caused by the THC. The hurdle met in the clinical trial also presents a patent issue as it is necessary for a patent to enable the skilled person to use the invention across the breadth of the patented claims.
There is also a potential issue with public morality regarding patentability especially if a large proportion of people find it abhorrent, which is less likely considering the medical use of cannabis.
Given the growing liberalization of the use of cannabis on both the UK and US it is still early days from a patent standpoint. The major issue still stands of obtaining clinical proof of benefit for these compounds and this can make it a compliance headache for companies to get involved in this area. However it is likely that with this wave of liberalization will come legal relaxation on these previously banned substances.
Novartis has been delivered another ‘no’ for its migraine treatment Aimovig from NICE following draft guidance which rejected the drug earlier this year.
The final appraisal supports the original decision that was made, that Novartis lacked a significant amount of data which meant it could not recommend the treatment for routine use on the NHS. NICE said the trials of Aimovig “excluded people for whom all previous treatments had no therapeutic benefit.” This significant population, largely represents those that would be most in need of the treatment and the “most clinically important subgroup."
With further reference to the data, NICE pointed out that no-where in the long term data was there proof that Aimovig presented a clear sustained benefit, and that it only included people with episodic migraine and did not specify how many previous treatment they had failed before taking the drug.
The agency also presented concerns that for the chronic migraine subgroup , there was no direct comparison with the current treatment in use (Botox), so its superiority is uncertain.
As a result, NICE determined the cost-effectiveness estimates are higher that what is deemed acceptable even with Novartis offering NICE a confidential discount to the £5,000 per year list price.
Novartis has responded that it is very disappointed in the decision, believing that it does have benefits over the current standard of treatment, including its self-administering dosing which means patients do not have to repeatedly attend clinic appointments.
Aimovig is avaliable for use in NHS Scotland and NICE has been met with criticism for establishing a post code lottery of success with those who cannot afford the medicine cut off from the potential benefits of the drug. Chief Executive of the Migraine Trust, Gus Baldwin, has said that it is a “very bad day for chronic migraine patients”
Since being approved by the European Commission in 2018, Novartis has seen rivals emerge from Eli Lilly and Teva. However Aimovig has managed to establish itself as the lead product in the market, with estimated sales of $2.05bn in 2024 by Evaluate Pharma.
NAO has reported there is still a lot of work left to do to prevent medicine shortages, despite the UK governments preparedness programme.
There are still significant gaps in No-Deal Brexit report, according to the National Audit Office
NAO has reported there is still a lot of work left to do to prevent medicine shortages, despite the UK governments preparedness programme.
One of the concerns put forward by the NAO is that the government has an incomplete picture of the stockpiling of six weeks’ worth of medicine and other medicinal products that are needed such as gloves and syringes. As of the 20th September, 72% of medicinal products had that amount available.
However, supplies of other goods other than medicines for social care providers ‘have not been similarly stockpiled’ creating issues for the home sector as it relies on non-medicine supplies that are not usually bought via the NHS.
There is still work being completed to arrange for additional freight capacity but there are worries it will not be ready for the 31st October in particular the extra ferry capacity that the government has contracted to bring in medicines into ports other than Dover. This is extremely important because of the 12,300 medicines used in the UK, 7,000 come from or via the EU according to the Department of Health and Social Care.
The APBI have welcomed that the government has placed top priority for the additional freight capacity, but they are adamant that stockpiling alone is not enough and that they need to be able to be replenished.
The government has assumed a worst-case scenario that the flow of goods over the Channel will be reduced by 40-60% and hopes that it will have as much of the freight capacity for priority goods as possible in place by 31st October and all of it by the 30th November at the latest. The government also has provisions in place to deploy a courier service that will fly in emergency supplies if needed.
The Department of Transportation has also been asked to procure an extra 2,326 additional heavy goods vehicle spaces per week as part of the government-secured freight capacity, with 91% of the additional spaces allocated to health and social care supplies.
Roche-Spark Therapeutics deal receives small advance in the UK, but M&A watchers continue to be uneasy
Roche’s pending $4.8bn pick up of Spark Therapeutics has been delayed continuously by the US and UK regulatory agencies. On Wednesday this week, the UKs Competition and Markets Authority (CMA) opened the public comment for its antitrust investigation of the deal.
So far, the CMA has announced that it will not push the Roche-Spark deal back as far as its US counterpart. This seems very insignificant news, but market watchers’ interest has rocketed as other mega-pharma deals have been started to be met with greater scrutiny from both patient groups and politicians. With the main worry arising that one potential blocked merger based on antitrust grounds would spell inevitable trouble for the other mega pharma deals.
A particular example that had watchers confused and escalated the worry was the Federal Trades Commission (FTC) role in BMS $74bn acquisition of Celgene with a demand that left many investors confused as the FTC ordered Celgene to divest its $1.6bn per year psoriasis med Otezla on the middling grounds of an overlap with a BMS investigational candidate. This left many analysts puzzled particularly as Otezla lacks the star power of marketed rivals such as Humira. Analysts at Jefferies see this as a potential read through that the FTC is being tougher on regulating competition.
Novartis has given the FDA a plan of actions it will implement to prevent an event like the Zolgensama data scandal from happening again, but the big pharma company continues to be adamant that the blame lies squarely on the two AveXis executives.
Novartis states that AveXis co-founders, Brian and Allen Kaspar, either directly manipulated the data themselves or pressured employees to do so. As well as alleging that they held up the internal investigation that Novartis submitted when it found out about the case.
Novartis has decided to shift AveXis’s quality control function in-house with a new senior executive appointed to oversee the process and future compliance. Also part of the remediation plans is a whistleblower scheme across AveXis, to encourage reporting of misconduct and fraud as well as a programme to retrain AveXis’s quality unit employees and Novartis stated that they will let the FDA know within five days if it receives credible allegations.
This move by Novartis effectively shifts the light that garnered attention from the FDA and the public simultaneously. Primarily that Novartis was aware of the manipulation of the animal testing data included in its submission before Zolgensama was approved but only told the agency after receiving marketing authorization in the US. It was this element of the scandal that brought Novartis the attention of US lawmakers.
At the annual Labour party conference in Brighton, Labour party leader Jeremy Corbyn announced his plans ‘to take on pharmaceutical companies.’
The initiative called Medicines for Many, was created to take aim at pharma companies that were placing shareholders earnings over people’s health and access to treatments. Aspects of the proposal included that patented drugs would be subject to compulsory or ‘Crown Use’ licensing which would mean that generic versions of these drugs could be manufactured at lower costs. The initiative also outlined a plan for a state-owned pharmaceutical company which would manufacture these generic medicines. This state-owned company would then go and sell its generics to the NHS and re-invest profits into “publicly funded research and development facilities.”
The Labour party leader was keen to highlight the case of Luis Walker, a CF patient who has been at the forefront of a multitude of campaigns for access to Vertex’s Orkambi. The public battle between the pharma company and NHS/NICE has been very publicly covered and met with overt criticism as frustrated patient groups have decided to bypass the system to source generic copies of the drug and establish a buyer’s club. Jeremy Corbyn highlighted the fact that Luis Walker cannot get access to this treatment because Vertex pharmaceuticals refuses to sell the drug to the NHS for an affordable price.
The British Pharmaceutical Industry has not taken this news well and responded that the proposal of compulsory licensing is not the right answer. Richard Torbett, executive director of commercial policy at the ABPI, recognized how the Luis Walker case is an unacceptable situation but that ‘commercial licensing’ which is ultimately seizure of new research, is not the answer. It would undermine the system for developing new medicines and send a negative signal to British scientists and discourage research in the UK.
Richard Torbett also highlighted the issue that the proposed plans would severely impact SME pharma companies, companies that are critical in the development of innovative medicine.
Novartis did not wait for an FDA investigation as it halts worldwide distribution of its generic Zantac, after it was suspected that a cancer-causing impurity had been detected in the popular over the counter anatacid.
The FDA decided it was unnecessary for Novartis to recall the generic however European and Canadian regulators have taken a more aggressive approach by asking drug makers to stop distribution. Unlike a recall it means the stocks of the drugs already in the store can be sold.
Novartis announced: “A precautionary distribution stop of all Sandoz ranitidine containing medicines in all their our markets will remain in place until further clarification.” Novartis is set to perform an internal investigation to determine further details.
Sanofi, which sells branded Zantac, has decided not to take a similar approach, with no current plans to stop the distribution or manufacturing of Zantac. Sanofi is said to be working close with the FDA and has pointed out to the regulatory agency that the level of NDMA in Zantac barely exceeds the amount found in common foods.
NDMA is the same impurity that set of global recall in blood pressure medicines last year, with the FDA determining in the recall that NDMA and two other cancer causing agents can be created during certain manufacturing steps involving the use of solvents. The FDA has now set acceptable limits to the amount of NDMA than can be found.
Microsoft has nominated GSK CEO Emma Walmsley as new Microsoft Board member, with the appointment set to be confirmed at the annual shareholders meeting on December 4th.
Walmsley is currently the co-chair of the Consumer, Retail and Life Science Council, an advisory group for the UK government, as well as an honorary fellow of the Royal Society of Chemistry.
This appointment could bode extremely well for both companies’ future ambitions as GSK seeks to accelerate its digital transformation and Microsoft is eager to wade deeper into the healthcare industry. Walmsley has been quick to improve GSKs digital expertise, by creating a new position of chief digital and technology officer a role that is to develop digital, data and analytics strategy for drug R&D. As well as in 2018, GSK created a new London based consumer healthcare digital innovation hub that brings together commercial and R&D functions to offer consumer facing digital solutions.
Microsoft has not been idle entering the healthcare market either, with the creation of Microsoft Healthcare in mid-2018 bringing Microsoft’s data and software capabilities to “help healthcare providers, biotech companies and organizations around the world to use artificial intelligence and the cloud to innovate.”
More relevant to GSKs hopes, is Microsoft recent collaboration success with St Judes Children Research Hospital to create what is said to be the world’s largest public repository of pediatric cancer genomics data, which aides tremendously for researchers in their drug development work. And with GSK focused on that sort of large scaled genetics project, shown by its previous £40m investment into the UK BioBank to sequence genetic data from 500,000 volunteers and its £300m equity investment into 23&Me as a part of bigger plan to utilise genetic and phenotypic data to streamline clinical enrollment and drug target discovery. This appointment bodes well for GSKs entry into the genetic data market which will hopefully accelerate its drug discovery and enhance its future pipeline.
The paper published by the BMJ examined 41 cases between 2014-2016 that were used to support the approval of 32 cancer drugs. The researchers found that 19 of them (41%) were at high risk of bias for their primary outcome, with the issue of bias arising because of missing data or by the parameters used to measure efficacy.
Trials that used overall survival as the primary endpoint (26% of the sample) were less likely to be at risk of bias than those that used surrogate endpoints such as progression free survival. With researchers further pointing out a substantial shift towards the use of surrogate studies in cancer trials. However, it is also important to note that in some cases bias risk ‘may be unavoidable’ due to the complexity of cancer trials.
There have been some suggested changes to approaches for the validity of trials, with many physicians facing big obstacles in trying to make treatment decisions but struggling to make supported choices due to methodological details of the trial data being scattered across different documents.
Physicians would like a standardized approach to collating and communicating information about the validity of trials, with suggestions including a risk of bias assessment in European Public Assessment Reports published by the EMA.
Additional suggestions include that the European Clinical Trials Register also demand the submission of a bias assessment alongside their trial results.
There is a concern that the rush to get new cancer drugs to patients as quickly as possible is starting to raise serious concerns about low standards of evidence supporting new cancer drug approvals.
The proposed app will aim to improve mental health in patients with multiple sclerosis. It was created in partnership with mental health digital therapeutics firm, Happify Health, with the app currently in a proof-of-concept online trial with several thousand MS patients. Statistics shows that MS patients are two- five times more likely to develop major depression than the general population.
After the results come through later this year, Sanofi plans to submit the app to the FDA for approval under the guise of a medical device. The app will be Sanofi’s first proposed digital therapeutic with MS carefully chosen due to Sanofi’s expertise in its understanding of the disease.
Sanofi has used its expertise in MS to incorporate specific medical and scientific needs into the base software platform by Happify Health, which is already in use for a non-specific solution in anxiety and depression with currently 4 million users.
This is Sanofis first move into the digital therapeutic area, but it is not the first pharma company. With the first FDA approved digital therapeutics product going to Pear Therapeutics reSET app to treat substance abuse, launched in partnership with Novartis Sandoz last year.
Roche’s prolific trio of mega blockbuster cancer drugs face an unsteady path as biosimilars loom in the distance. With the drugmaker predicting that a loss in these products will cause a $10bn dent.
However the company remains confident that the growth of newer drugs in its pipeline will be more than enough to offset that dent.
Roche has even laid out its calculations with it assuming a 60-70% ‘conservative’ erosion from biosim competition, leading to a sales gap of $9.6bn between 2018-2023. But they also added that by 2023, the companies recent launches and up and coming pipeline could turn up an addition $16.3bn. However these are very big ‘ifs’ and ‘buts.’
Roche expects the effect of biosim in the US to be much slower compared to Europe, as the biosim market in the US is still trying to find its footing. But Roche should beware about using past biosim experience in Europe or the US, as a lot of biosim products currently in market, were against products that are not the standard of care or have been somewhat commoditized with high levels of discounts etc. In the case of Roche, its three cancer blockbusters are none of the above.
Leading the pack for Roches new growth drivers is its Multiple Sclerosis drug Ocrevus, a drug that has been crowned “the most successful launch in the history of Roche”, adding an additional $3.8bn to Roches top line in 2023 compared to 2018. In the first half of 2019, Ocrevus grew sales by 63% to CHF 1.7bn.
Merck&Co/MSD have become the first company to file for approval of an Ebola vaccine in the US, with a result expected in March next year after the FDA has given this case a priority review.
The vaccine has already been granted approval for use in emergencies by the World Health Organization (WHO) based on trials conducted during the 2014-16 Ebola crisis in West Africa, where it was found to have 93% protective efficacy.
It is now also under regulatory review in Europe with Merck eager to achieve registration and regulatory approval for its German manufacturing site, so that a licensed supply can be produced over time to support global public health preparedness and health security objectives.
This rapid move for approval stems from the recent outbreak in the Democratic Republic of Congo, where there has been a reported number of 3000 cases at the end of August, making it the second-largest epidemic of the virus ever. The death toll stands at nearly 1000, reminding us of the deadliness of the virulent strain.
More than 200,000 people have been vaccinated in the country either by Mercks product or by another experimental vaccine by J&J. The vaccines have been administered in a ring vaccination strategy, with the vaccination radiating out from those in contact with diagnosed cases of the infection in order to try and contain its spread in the absence of mass immunization.
Lundbeck is offering $18 per share for Alder, with an additional $2 per share if Alder gets approval by the European Medicines Agency (EMA). It is due to be reviewed by Europe early next year but is already under regulatory approval in the US.
This move comes from Lundbeck, specialist in CNS disease therapies, as an attempt to build up its pipeline after it is set to face a series of patent expirations.
The prize drug of Alder Biopharma is Eptinezumab, a new migraine prevention drug in the CGRP inhibitor class, but unlike marketed rivals from Amgen/Novartis it is delivered intravenously rather than by subcutaneous injection. Further advantages for Alder is that their drug is administered every 3 months while Amgen’s and Eli Lilly’s are taken once a month.
Eptinezumab will be the fourth CGRP inhibitor to go on the market, but it will have to do some catching up as the current CGRP inhibitors are only starting to make waves after some initial payer resistance. With first to market, Aimovig bringing in $83m in sales in Q2 followed by £34m for Emgality.
This acquisition by Lundbeck is one of many, as it brought Abide Therapeutics for $400m earlier this year adding a mid-stage drug for Tourettes syndrome and its $1bn acquisition of Prexton Therapeutics last year acquiring phase 2 Parkinson’s disease therapy, foliglurax.
Lundbeck was not always a major M&A player but under new CEO, Deborah Dunsire, they have moved away from in-house R&D and smaller scale licensing deals to picking up the pace with major deals.
In another blow to the BACE inhibitor category, Biogen and Eisai have dropped the trials for elenbecestat due to the Data Safety Monitory Board finding that the drug had an ‘unfavorable’ risk-benefit ratio.
This news comes after similar results were reported with Amgen and Novartis after they abandoned phase 2/3 studies of BACE1 inhibitor as some participants found their condition worsening than those on placebo. Merck&Co, Janssen and Eli-lily have also reported similar trends with their results regarding BACE inhibitors.
BACE inhibitors target the beta amyloid cleaving enzyme (BACE) which plays a role in the production of beta amyloid peptides. The hope was that reducing the production of beta amyloid peptides would reduce amyloid plaques formations in the brain and thus slow the progression of Alzheimer’s.
The two pharma companies now only have one amyloid-targeting drug left in their pipeline, which will proceed unaffected from the current result read-out. However, there is a growing consensus that the ‘amyloid hypothesis’ of targeting beta amyloid has all but been exhausted. With companies now putting in the effort/funds to targeting other mechanisms of the disease.
The FTC (Federal Trade Commission) has been urged by advocacy groups to consider blocking the $63bn merger between the two pharma giants.
Members of the advocacy group include Public Citizen and the American Federation of Teachers with the letter to the FTC stating: “we request that the Commission investigate this proposed merger thoroughly and take all necessary action, includ(ing) blocking the merger, to prevent further harm to consumers.”
The primary concern from the Advocacy group arises from the fact that if the company were to merge it would become the fourth largest pharma company. And they worry that the company would use this newly emphasized power and size to increase the use of volume-based rebates or other incentives to insurers or pharmacy benefit managers. There also continues to be concerns that the merger could lead to dominant market share in certain therapy areas.
This merger has continued to split investors and analysts. With one half in the mind along with AbbVie that this deal will add $16bn annually to revenues that will help to preserve the bottom line when the US patent for $20bn blockbuster Humira expires.
However, there are those that believe the deal is adding AbbVie with debt and doing little to diversify AbbVie’s pipeline. And with Allergan’s blockbuster Botox facing increased competition from migraine drugs and medical aesthetic drugs, that source of revenue can also not be depended on.
AbbVie’s chief legal officer, Laura Schumacher told analysts that AbbVie does not expect significant issues with the FTC approval process but added there are a few small product overlaps that they have agreed to divest promptly.
A draft of the Drug Price Negotiation Bill from Nancy Pelosi, which is still being tweaked was leaked.
According to the document, the maximum price negotiated for these 250 drugs cannot be more than 1.2 times the average price in six countries referenced as indexes. These six countries being UK, Australia, Germany, France, Canada and Japan.
The 250 chosen drugs are those that are costing Medicare the most every year. This is based on metrics such as each drug each not having at least two “generic, biosimilar or interchangeable” competitors in the marketplace.
Also included in the pricing plan is the proposed method of action of imposing hefty penalties amounting to 75% of gross sales of a product in the previous year, if pharma manufacturers do not reach an agreement or choose not to enter negotiations.
The list has been viewed in two distinct mindsets, with a view seeing it as a way of attempting to find a middle ground between Trumps across the board reference pricing plan and established Republican resistance to allowing Medicare to negotiate pricing on the grounds that it runs counter- to free-market principles.
This prominent resistance particularly in the Republican majority senate means this bill could find it very hard to get through the Senate. In a summary of the document, it claims that within the first year of the bill “drugs representing almost half of all Medicare Part D spending…would be subject to the negotiation process -including insulins.” With the latter part raising interest with the recent press around the high insulin prices charged to US patients.
Medicare Part D provides private health insurance to around 25 million people in the US. Also according to the draft, all 8,000plus drugs covered in Part D as well as drugs which are prescribed by a physician in a hospital (Medicare Part B) would be subject to a mandatory rebate if their prices increased beyond the rate of inflation since 2016.
The Danish drug maker said it would release an authorized generic version of NovoLog at around $145 per vial, roughly half the branded drugs current list price. It is set to release the authorized version in January 2020.
This move follows decisions made by Sanofi which it said in April that it would reduce the cost of insulin for uninsured people to $99 per month and well as Eli Lilly which has now offered a 50% cheaper version of its Humalog.
It is also set to launch a cash card programme next year, which will make around a month’s supply of any of its older analogue insulin products in vial or pen formats available at $99, for patients with or without insurance.
However, there has been a public outcry regarding Eli Lilly, where patients have said they have had difficulties in getting hold of the authorized generic and accused the company of performing a publicity stunt of announcing a cheaper product that in reality is in very little supply.
The fight about insulin prices started in 2017, where it was revealed that insulin prices tripled over the years from 2007-2017. The three mentioned companies were summoned to a Congressional hearing to explain the steep rise in drug prices, where they denied responsibility, citing the complex US healthcare system as the issue in particular the pharmacy benefit managers (PBMs) which the drugmakers claim have a vested interest in keeping the list prices high.
AZ has revealed impressive results from its Caspian trial for its immune-oncology treatment Imfinzi, revealing it improved Overall Survival by 27%.
AZ has been looking for approval for Imfinzi in combination with chemotherapy since June this year for Small Cell Lung Cancer (the most aggressive form of lung cancer.) At the World Conference on Lung Cancer (WCLC) lead investigator Luis Paz-Ares told delegates that Imfinzi plus etoposide chemotherapy achieved a mean Overall Survival (OS) of 13 months, compared to the OS of 10.3 months when just using chemo alone.
The question now facing AZ and regulatory agencies is whether Imfinzi can challenge Roche’s recently US approved Tecentriq. From the outset, the initial results are similar with Roche’s drug extending survival to 12.3months when added with chemotherapy. However where AZ differentiates itself is that the drug has shown an increased durability of response.
After 12 months, Progression Free Survival (PFS) was 17.5% compared to 4.7% with chemo, with the duration of the response also better at 22.7% versus 6.3% respectively. AZ Imfinzi’s also had the added advantage of the CASPIAN trial looking at multiple chemo options, giving physicians more choice and catering for varying changes in clinical practice.
Although this spells good news for AZ as it seems it will be able to challenge Roche in first line treatment for SCLC. Both competitors will be wary of Merck and Co, whose current treatment already reigns supreme in NSCLC (Non-Small Cell Lung Cancer), which has already been approved for use in third line treatment of SCLC and has an upcoming trial for first line SCLC.
AstraZeneca reveals spectacular data at the European Society of Cardiology for its heart failure drug Farxiga
AZ had previously revealed that the DAPA-HF trial was a win for their Farxiga treatment, but now we have figures to understand their glee.
Lead Investigator, John McMurray of the University of Glasgow, presented the data in Paris last weekend. He said that Farxiga reduced the composite of cardiovascular (CV) death or worsening of heart failure by 26%, with these benefits seen in patients both diabetic and non-diabetic, when added to standard therapy.
At this conference, cardiologists were able to see the scale of improvement with the SGLT2 inhibitor, which had positive impacts across all 14 prespecified subgroups in the trial. Farxiga also reduced the risk for all-cause death by 17%.
Farxiga is the first drug in its class to complete a cardiovascular outcomes trial in HRrEF and could open up a new treatment category for these patients and open up a new revenue stream for AZ as it tries to catch up to current market leader Jardiance from Eli Lilly and Boehringer Ingelheim.
In reference to the DAPA-HF trial, Marco Metra of the University of Brescia in Italy described the trial as a ‘landmark trial’ that could usher in “a new era in heart failure medical treatment”
Farxiga has already grown big for AZ based on the data showing that it reduces CV and kidney complications in diabetics, but this DAPA-HF trial could extend its use into the non-diabetic population and make in an option for the millions of patients worldwide with heart failure.
HRrEF is a category of heart failure and accounts for around half of all cases, Farxiga is also hoping to get approval for HRpEF (Heart Failure with preserved ejection failure), a hard to treat form of the disease that currently has no approved drug therapies. Farxiga is currently being studied in relation to HRpEF in two trials.
Eli Lilly and Boehringer are not waiting to be left behind as they have recently won a fast track review from the FDA for Jardiance in both HFrEF and HFpEF based on the results from two trials.
AZ can expect sales to go up a gear if data is cleared by regulators. Farxiga brought in sales of $1.4bn for AZ last year, just over half of the $2.7bn for Jardiance and it grew by another 14% to $726m in the first half of 2019.
The recent patent challenge by Amgen has not brought a lot of good news for Alexion pharmaceuticals. Alexions shares have dropped by more than 15% since the news was announced that the US Patent Office would review key patents behind Solaris, the key drug for Alexion that made up 88% of Alexions sales in 2018.
SVB Leerink analysts updated Amgen’s patent challenge to a 50% success rate with an additional 8-12% ‘incremental erosion’ to Solaris sales beyond 2022, when Amgens biosimilar challenger would likely hit the markets.
JP Morgan Analyst, Cory Kasimov, called the investor reaction overblown. As well as stating that in the worst case scenario, Amgens biosimilar would come on the market in 2022, which gives Alexion more than enough time to switch patients to Ultomiris.
Alexion is already ahead of the game because as of July around 40% of Solaris patients have switched to Ultomiris, putting Alexion well on track towards its planned 70% conversion rate by 2020. Ultomiris already has a Solaris matching approval as well as a cheaper price than the older drug.
Another plus for Ultomiris is that even if Alexion has a setback in meeting its conversion plans, Solaris still has orphan drug designations that would secure US exclusivity in certain conditions until later dates such as neuromyelitis optica (NMO) unit mid 2026.
Ultomiris which is seeking approval in NMO, could launch in this indication as soon as 2022, giving Alexion and even better chance of switching patients away. For an Amgen biosimilar to make a real challenge the copycat will have to be at an extremely compelling price that could be daunting to achieve.
Vertex is to pay $950m in cash for the Cambridge, MA based biotech firm and will acquire all outstanding shares of the firm. Semma will become a subsidiary of Vertex pharmaceuticals, with Semmas CEO set to join Vertex and continue as the CEO.
Semma was founded to develop therapies for type 1 diabetes patients who depend on insulin injections. It is a pioneering firm, with its use of stem cell research as a potential cure for type 1 diabetes. The biotech has been able to produce large quantities of functional human pancreatic beta cells that restore insulin protection and ameliorate hypoglycaemia in animal tests. In addition to these findings, the biotech firm has developed a device that captures and protects these cells from the immune system, which in turn allows for durable implantation without the need for ongoing immunosuppressive therapy.
This deal for Vertex follows a string of others as it seeks to diversify its pipeline portfolio from its Cystic Fibrosis franchise. The company has been a pioneer in this field with it recently submitting approval for its landmark triple combination therapy. If approved this treatment would be a huge gamechanger for Cystic Fibrosis sufferers, where it could be used to treat 90% of all CF sufferers worldwide.
This acquisition of Semma will set up a rival for Novo Nordisk, where last year the Danish company secured a milestone in the same area of stem cell therapy in type 1 diabetes. The first clinical trials for both companies could begin within the next few years, setting up a potential race to first in class.
In the 1980s only 4% of the drugs that were approved by the FDA were cancer treatments, but since 2010 cancer treatments have secured 27% of the new approvals. These claims come from a report from the Tufts Centre for the Study of Drug Development.
This meteoric rise has been accredited to pharma companies taking a smarter approach to drug development with a focus on developing novel mechanisms for treating cancer and further validating them with clinical trials that have been improved in their design and efficiency. This is supported by the fact that Pharma companies can now identify new gene targets as well as design trials around patients that are more likely to respond to the treatment. This coupled with the FDA’s push to increasing its efforts to speed up medicines to market that address unmet medical needs can also explain this new wave of cancer treatments.
According to Tufts, the development timeline for cancer drugs was 9% longer than it was in other diseases from 1999 and 2018, but the time taken for the FDA to approve it was a dramatic 48% shorter. This is because cancer drugs are much more likely to receive special designations from the FDA designed to speed up the regulatory process.
A particular sub-section of cancer treatments that seems to be generating a lot of these approvals are kinase inhibitors. With Wall Street firm, SVB Leerink finding that kinase inhibitors have driven nearly $100billion in M&A since 2010. Furthermore, FDA also seem to have their eyes on kinase inhibitors, with 77% of the kinase inhibitor products being evaluated under priority review.
The big downside to all these cancer approvals is that it does not come cheap to either party be that the pharma companies and the healthcare system. With Tufts estimating that the cost for developing any prescription drug amounting to $3bn and oncology manufacturers spend on average $13m just on the launch phase for a single cancer drug in one indication.
As a result of these huge expenses, companies have to drive prices to recoup these expenses. With the 15 oncology drugs approved in 2018 coming with an annual median cost of $149,000.
Consumers now think less of the pharma industry than any other industry. It replaced the federal government in the annual Gallup poll that asks Americans for their views of 25 industries.
The Gallup is a poll that asks Americans sentiments on the biggest industries by asking respondents to rate their view based on the metrics of very positive, somewhat positive, neutral, somewhat negative, very negative.
Americans are more than twice as likely to rate the industry negatively (58%) as positively (27%) giving it a net score of -31. This score is the lowest the pharma industry has ever received since the polls inception in 2001. So bad is this score, that Gallup stated very few industries have ever scored lower than -31. With only the government, oil and gas and automobile ever falling below this value in the past 19 years.
Gallup has pointed out that this fall from grace stems from the waves of criticism that industry has been facing recently for its standard norms such as “generating the highest drug costs in the world to spending massive amounts in lobbying to the industry’s role in the US opioid crisis.” What is even more worrying for the industry, is that this poll was taken in early August before the recent court ruling against J&J in Oklahoma over its role in the opioid crisis.
Gallup says that not all is lost and that the industry can make gains in the next few years, bringing up past examples of the real estate industry in 2008 posting a score of -40 and as of 2019, real estate placed in the top 10 among Americans.
The industry to top the list this year with a score of +58 is the restaurant industry, followed by the computer industry with +50 and the grocery with +43.
Novartis had set high hopes for its Entrestro cardiovascular medication, with the company forecasting peak sales of $5bn. Now a huge trial setback has forced Novartis to lower its lofty expectations. But Novartis have not completely written of the drug, citing there is positive news as it was only a ‘narrow miss.’
Entresto reduced the combined rate of heart failure hospitalizations and cardiovascular death among heart patients by 13% according to the data from the phase three trial. However this reduction failed to meet any statistical significance.
Entresto narrowly missed its primary end-point, but the drug still showed improvements in patient quality of life as well as strong results in particular patient subgroups such as patients with a left ventricular ejection fraction equal to or below the median of 57%.
David Soergel, Novartis’s head of cardiovascular renal and metabolic drug development stated: “What we see in the data is clear evidence that Entresto has drug effects and potentially beneficial effects just based on the totality of the data.”
Despite the setback, Entresto has seen a huge surge in sales in the last few months, including the $1.08bn hit in 2018, after a slow response after its 2015 approval. Novartis had high hopes the drug would become a cash cow predicting sales of $5bn. In the second quarter, Entresto posted a quarter over quarter sales jump of 81% to hit $421m.
However, Entresto is one of many cardiovascular flops for Novartis, as the FDA rejected another candidate to treat patients with prior heart attacks. In that particular case, the FDA rejected the approval after acquiring more data from the drugs phase three trial.
Luxturna, a gene therapy used to treat a rare, inherited form of blindness will now be available for routine use in the NHS in England and Wales.
It is a one-off treatment and it was backed last November for both children and adults who are living with vision loss due to genetic mutations. It is estimated to affect around 180 patients and patients almost invariably end up losing their sight entirely.
Along with the gene therapy, patients will have to have sufficient retinal cells remaining for the treatment, which will involve a one-time injection under the retina. The company and NHS have agreed on a confidential discount of the list price of £613,410 for the therapy.
Novartis secured the rights for the treatment outside of US from its original developer Spark Therapeutics last year, shortly after the biotech received FDA approval for Luxturna. Since this approval. Roche has been hot on Spark Therapeutics heels in trying to take over the biotech firm, in a deal estimated at $4.3bn. However the deal has been setback multiple times due to anti-trust concerns by regulators from the UK and US.
The Scottish Medicines Consortium will deliver its verdict on the gene therapy in December.
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