This past year there has been a huge wave of lawsuits and backlash against big pharma companies for their responsibility in exacerbating the opioid crisis in America.
A multitude of companies have been blamed and been taken to court, incuding companies such as Teva Pharmaceuticals, Purdue Pharma, Allergan, Mylan, Amneal, Endo Pharmaceuticals and ‘Kingpin’ of the opioid crisis Johnson&Johnson. Both Teva and Purdue pharma settled with Ohio state as the case approached trial and both Allergan and Endo settled with two Ohio counties for a combined $16m.
However, the state attorney is not letting Allergan and Endo of the hook, with the state of Ohio planning to fully prosecute both companies. Ohio’s state Attorney General said in a statement “No settlement with any political subdivision(s) relieves Allergan PLC of any liability to the state for any claim that Ohio has brought.”
Endo’s $10m settlement with two Ohio states acted as a bellwether case for the massive multidistrict litigation involving around 1,600 counties and cities. A bellwether trial is a test case intended to trial a widely contested issue. According to analysts, this Endo settlement could come as a relief to companies and offers a breath of fresh air for companies facing the prospect of bankruptcy. This good news carried out to Allergan, which agreed to a $6m deal.
However, the prospect for Teva pharmaceuticals is uncertain, with the company previously reaching an $85m deal with the state of Oklahoma. But it is unclear how the global settlement would allocate damages.
Oklahoma has not shied away from taking the battle to the big pharma companies with the county taking J&J to court. Oklahoma has labelled J&J as the ‘kingpin’ of the state’s opioid crisis in the first ever bench trial assessing whether a drug maker fueled an epidemic. The results of the case are set to be announced this coming Monday and the verdict could inform the chances of 1,600 consolidated lawsuits against opioid makers. J&J’s fault comes from its “deceitful, multibillion-dollar brainwashing campaign” to boost sales of its powerful and potentially addictive opioids. The Attorney General said J&J driven by corporate greed induced doctors to boost opioid prescriptions to treat unapproved ailments.
J&J has said in its defense: “Not once did the state identify a single Oklahoma doctor who was misled by a single Janssen statement, nor did it prove that Janssen misleadingly marketed opioids or caused any harm in Oklahoma.”
The state went on to say that J&J scientists created a mutant poppy strain in 1994 that allowed the company to produce mass quantities of opioids. J&J then went on to conduct ‘a decade and a half long’ unbranded marketing campaign to pitch opioid drugs as safe for everyday pain. J&J has rebuked these claims saying that operations were heavily regulated by the Drug Enforcement Agency and that it held a ‘miniscule’ fraction of the opioid prescription market.
The decision on Monday could have major consequences for not only opioid crisis in the US but also overseas as well as other countries acquire their own opioid addiction problems.
Rumors have been circling for the past year that Amgen is looking to strike a deal with Alexion pharmaceuticals to prop up their pipeline. Now that this rumor has resurfaced again, investors are delighted as a deal would help prop Amgen against the $2bn fall it is expected to face as two of its blockbusters Neulasta and Sensipar are set to experience biosimilar competition. An Amgen-Alexion deal would boost earnings for Amgen next year and lead to a 20% earnings accretion by 2024.
On Wednesday, Spain’s Intereconomia reported that Amgen is on the verge of acquiring Alexion for $200 per share. Analysts are skeptical about the validity of this source, but this has not stopped Alexion’s stocks from shooting up by more than 7% to $123.49.
Alexion has long been on analysts watch list for companies that are likely to be acquired particularly due to its profitable but manageable pipeline of drugs such as its $3bn a year drug Soliris which treats rare blood and neurological diseases. As well as its low valuation, with the company’s share price being mostly flat since it received approval for its product Ultomiris last year.
Amgen continues to face pressure from investors to engage in a big biopharma merger, with analysts looking into reasons why Amgen seems so hesitant. Some believe it could be due to recent Federal Trade Commission (FTC) decisions, that seem to be having a stricter and stricter approach to big deals, such as its insistence for Celgene to divest its blockbuster Otezla.
Amgen has stated before that “it struggled to find transactions at prices that we think can earn a return for our shareholders. But again, we continue to look for opportunities and fully expect that by being disciplined we’ll find ones that enable us to win for our shareholders and to invest in programmes that can help us grow the company.”
Az’s immune-oncology combination of Imfinzi and tremelimumab has failed to improve overall survival in a phase three trial, further undermining the chances of AZ presenting a challenge to Merck&co Keytruda in first non-small cell lung cancer.
The NEPTUNE study compared Imfinzi and tremelimumab with standard platinum- based chemotherapy in previously untreated patients with NSCLC. This was not the first trial to test this combination, initially there was clinical trial where it failed to make any significant difference however it showed signs of improvement in a particular subgroup of patients with a certain cancer biomarker. This prompted AZ to tweak the design of its trial to the present NEPTUNE trial which focuses exclusively on this group of patients.
AZ is obviously disappointed with the lack of improvement on OS compared to chemotherapy. With AZ’s head of Cancer, Josè Baselga, saying that the company “is fully committed to a deep analysis of the vast clinical and biomarker data from this trial to gain further insights to improve immune-oncology approaches for patients with metastatic non-small cell lung cancer.”
The result of this trial effectively removes the chances of Imfinzi challenging Keytruda. However, it is not all bad news for AZ, as Imfinzi does have a use as a maintenance therapy for locally-advanced NSCLC patients whose tumours cannot be removed surgically This approval came from its PACIFIC trial results last year, which helped to accelerate Imfinzi’s sales to $633m in the first half of the year.
It is also not the end of the road for Imfinzi, as AZ has another combination trial with Imfinzi and tremelimumab called POSEDION, with results to be read out at the end of the year. However, after this trial results, hopes have been significantly reduced. POSEDION is comparing Imfinzi, tremelimumam and chemo with an Imfinzi and chemo combination also comparing with just chemotherapy alone
Finch Therapeutics is a very interesting company specializing in using bacterial cultures to restore the natural balance of the bacterial colonies that populate our body (our microbiome) which diseases/drug therapies are able to disrupt.
The major player in Finch Therapeutics pipeline is its product CP10, an oral capsule that contains a diverse range of microbiota that can restore the bodies microbiome. At the moment it is currently being studied in Finch’s PRISM3 phase three clinical trial for the prevention of recurrent C.difficile infections. The company hopes that this money will help to push the trial towards pivotal results.
Earlier this year Finch Therapeutics secured a breakthrough therapy designation (BTD) from the FDA for CP10. This is huge news for Finch as it would mean that the FDA could help push CP10 ahead of other microbiota rivals.
The company also plans to use this new founded financing for its development programme for a treatment for Autism Spectrum Disorder (ASD). With the biotech firm currently evaluating the safety and efficacy of its product in a Stage 2 trial. Finch has a focus on ASD because sufferers often experience behavioral problems that are interlinked with gastrointestinal symptoms, with previous studies suggesting a link between the two symptoms.
Finch Therapeutics is not the only company seeing promise in the microbiota sector, with rival company Rebiotix presenting early data in 2017 that its microbiota suspension RBX2660 prevents recurrences of C.difficile infections. With Rebiotix currently enrolling patients in a phase three clinical trial to also study the safety and efficacy of its trial.
The microbiome sector has not gone unnoticed by big pharma with large companies spending big investments. In March this year, AstraZeneca paid US biotech Seres Therapeutics in $20m in instalments over the next two years, with reimbursements, to explore how the bacteria in the gut can affect and enhance cancer immunotherapies. And last June, Roche’s biotech subsidiary Genentech signed a $534m deal with UK biotech Microbiota to access its precision metagenomics microbiome platform to analyse samples of its clinical data for investigational IBD medicines.
Brian Kaspar, the recently fired Chief Scientific Officer of AveXis, has told his side of the story, he has announced that he has done nothing wrong and backed by former Elon Musk lawyer shows he’s not playing around. Law firm, Heuston Hannigan, stated that Kaspar “categorically denies any wrongdoing” and that he is prepared to “assert his rights and defend his conduct accordingly.”
A brief summary of the situation is that Brian Kaspar and his brother Allan, former lead scientists ‘left’ the company in early May at around the same time that Novartis found out internally about the data scandal but also month before Novartis told the FDA about the manipulation.
Novartis had previously stated that it has terminated ‘a small number of AveXis scientists’ which looks like the Kaspar brothers stand among these few. However, it is unknown on what grounds Kaspar where fired now that Brian has denied any wrongdoing, could it be they were let go due to oversight?
The answer should be coming soon, with Senate Finance Committee chair Chuck Grassley launching an investigation, requesting all records to Novartis internal probe it performed. With the deadline for the records set at Friday 23rd August.
It is also not known what path Brian Kaspar will take, whether he will sue his former employee for firing him. The FDA has announced that it will use its full authorities to act, which may include criminal and civil penalties against AveXis.
Pfizer is pushing the pedal towards producing the first major gene therapies, with this huge money injection set to send progress into overdrive. The manufacturing site will also employ a further 300 employees.
The larger plant will provide a large addition to its clinical and commercial scale production capabilities for its work on potential genetic cures using recombinant adeno-associated virus vectors.
The manufacturing plant started out at a much smaller scale when Pfizer acquired the plant in Sanford from biotech Bamboo Therapeutics. At the time it was expected to employee around 40 scientists, with this expansion increasing jobs by a further 300, this will increase the Pfizer headcount to an impressive 650.
Things are starting to come together now for Pfizer as this expansion will no doubt help towards its future gene therapy products in the pipeline. With Pfizer announcing last month positive results on the durability of responses to their haemophilia A gene therapy. With the confidential review also giving encouragement to those who believe that it will outperform rival products from Spark Therapeutics and BioMarin.
Hemlibra will now be available to a further 2000 patients living with Haemophilia A, a huge expansion into the market for an already very successful drug. Hemlibra achieved global sales of $538m in the first half of 2019.
The agreement between NHS funding and Roche would have no doubt involved tough negotiation on the behalf of the NHS, with the market access agreement once again being agreed through direct pricing. In these discussions there was no involvement from NICE.
This expansion follows the first agreement that was made on the 28th July for approval of Hemlibra in people with haemophilia A with inhibitors (antibodies that prevent patients responding to standard factor VIII therapies) of which this accounted for 230 UK patients.
This new expansion for patients without inhibitors, extends it by approximately 2000 patients. And with an estimated 5,930 patients registered with haemophilia A, this results in Hemlibra being available to around a third of all patients.
Hemlibra is seen as a preferred alternative to VIII replacement drugs because it has been proven to significantly reduce bleeding as well as providing multiple dosing options as opposed to factor VIII drugs which have to administered multiple times a week.
This news has been met with widespread approval with both the Chief Executive of the NHS and Chief Executive of the Haemophilia society praising the decision with both representatives highlighting the advantage of the reduced intravenous infusions that is required with current treatments.
However how long will Hemlibra have this success for, as Alnylam has a late stage candidate fitusiran which is widely tipped as a competitor to Hemlibra as well as the first gene therapies set to hit the stage as well, with BioMarin in prime position with its candidate valrox, which is to be submitted at the end of 2019.
The UK has lost its measle-free status just three years after the WHO (World Health Organization) declared that the country had eliminated the virus.
British PM, Boris Johnson, yesterday called for more urgent action to ensure children received the MMR vaccine to prevent the spread of the virus. In the first quarter of 2019, there were 231 confirmed measle cases in the UK, which the government said were mostly acquired abroad.
Measles can be prevented by receiving two doses of MMR vaccines. The number of children receiving the second vaccine dose has dropped to 87%, which the rates between children receiving the first and second doses lowest in London.
Boris Johnson has set a target to increase the vaccination rate to 95%, the standard target for measles elimination. The plans announced to reach this target include asking GP’s to promote catch-up vaccinations for children who may have missed both doses, urging social media sites to tackle mis-leading anti-vaccine messages and using the NHS website to address misleading claims about vaccines.
This is not just a problem centered on the UK, with the increasing global skepticism around the safety of vaccines giving rise to WHO administering the term ‘Vaccine hesitancy’ and labelling it as one of the top ten threats to global health in 2019. With data from WHO also pointing to that fact that measles is now endemic in countries such as France, Germany and Italy.
Expert blame the decrease in vaccination rates on ‘viral misinformation’ which has been spread around on social media sites likes Facebook and Twitter.
Pfizer surely expected a downturn in its sales of Lyrica, as generics hit the market in the US around three weeks ago, but I am sure they did not expect it to be this bad
According to figures posted by IQVIA’s SVB Leerink, Lyrica lost 35% of its market share to 16 competitors in the last week of July alone and the drugs shares of prescriptions fell to just 43% in the week ending August 9th. Its top competitors include Novartis Sandoz unit which took 9.7% of the market, Cipla with 8.1% and Amneal with 6.9%.
This is a shocking fall for Lyrica, which brought in $3.6bn in sales in the US in 2018. However, Pfizer may not be too worried as it heads towards its spinoff of its established products unit called Upjohn.
Pfizer recently announced in July the merger of its UpJohn unit with Mylan, a calculated move intended to pair down the company’s sprawling business and offload its flagging off-patent meds. Pfizer has previously said this unit could net $12bn which it would use to pay off debt and return shareholder dividends. Pfizer would ‘offload’ Lyrica and Lipitor onto Mylan.
This is still not to say that Lyrica should be completely written off, as comparing it to other Pfizer blockbuster drugs that lost their patent, it can be predicted that it will still perform well. For example, take long time blockbuster Lipitor that lost its patent back in 2011 as well as 90% of the US blood market share in that year. This brand still managed to bring in a blockbuster-worthy $407m in the second quarter. Therefore, I would say it’s reasonable to expect Lyrica to still perform well.
It is good news for BMS today, as the FDA finally approved Celgene’s treatment for myelofibrosis, Inrebic, as a first line or follow up treatment. This will be the first drug in nearly a decade to be approved for this disease. Myelofibrosis is a rare bone marrow disorder that disrupts the patient’s normal production of blood cells. However, it is not all good news as Inrebic will have to come packaged in a black box warning for potential serious and fatal encephalopathy (a general term for brain disease). As Celgene reported from its clinical trail results that serious encephalopathy was reported in 1.3% of trial patients treated with Inrebic and one of those patients actually died from the side effect.
Inrebic has passed through many hands in its lifetime with Celgene picking up the drug from its acquisition of Impact BioMedicines in early 2018, where before that it was developed by TargeGen and then acquired by Sanofi. Where Sanofi subsequently called of its clinical trials back in 2013 due to the FDA placing a hold on the drug.
This comes as good news for BMS, as Inrebic was one of the big 5 products that BMS was set to acquire after its takeover of Celgene. And after Multiple Sclerosis hopeful and other Big 5 member, Ozanimod, has been picked up by FDA again, it seems that events are finally starting to head in the right direction for BMS.
However, shareholders still remain to be convinced as they bring up the forced divestment of Celgene’s blockbuster Otezla (which racked up $1.6bn in sales in 2018) and a flurry of patent set to end, will accumulate a lot of pressure for the Celgene products.
Inrebic is a JAK inhibitor, a market that is soon set to become saturated as two more candidates approach the market. This includes AbbVie’s upadacitnib and Gilead Sciences filgotinib. This is a lucrative market as current JAK inhibitor leader, Pfizer’s Xeljanz turned in an impressive $613m in its second quarter.
A US court has sided with Sanofi in a patent dispute with a multitude of companies that want to produce generic copies of cancer drug Jevtana.
The ruling went back on its previous decision of deeming the Sanofi patent invalid. Actavis and Mylan had received tentative approval for generics of Jevtana, but Sanofi quickly responded by taking these two companies to court and appealing the invalid patent ruling. Sanofi used the merit of the previous ruling as a key part of its current court case.
In the appeal Judge Lourie found that: ‘The defendants’ experts cherry-picked data in the references to reach Jevtana and were not credible.’ The court recognized that Jevtana was only the third taxane cancer treatment to reach FDA approval despite attempts from research groups from around the world attempting to replicate. Thus the court ‘determined that Sanofi’s success where others had fallen supported non-obviousness.’ In patent terms obviousness is when an ‘invention’ or ‘product’ is not patentable because it is already known. A useful example I found on the internet was:
· You have invented A+B
· A is known in the prior art
· B is known in the prior art
· Upon looking at A and B, would someone of skill/knowledge consider A+B to be already known
· If the answer is yes, then A+B is obvious
· If the answer is no, then A+B is non-obvious
So, in the previous patent ruling the Sanofi treatment was ruled as obvious, which they subsequently challenged and due to a lack of credible data from other research groups to reach/match Jevtana’s trial results the court ruled the treatment as non-obviousness.
This is a success for Sanofi as it hopes to boost the money it is making out of Jevtana. Sales last year reached $468m an almost 10% increase from 2017. This made Jevtana Sanofi’s best-selling cancer drug, accounting for almost 30% of all oncology sales. As of 2019 currently, the sale of Jevtana has generated revenues of $263m, putting it on track for another year of growth.
The lawsuit is being filed by shareholders from Novo’s home country of Denmark with the suit alleging that Novo Nordisk made misleading statements and did not make appropriate disclosures regarding its sales of insulin products in the USA. It has been noted that the lawsuit is similar to the one Novo Nordisk faced before back in 2017 from US holders of the companies American Depository Receipts (ADR’s)
The shareholders demand a huge payoff of around $1.75bn in compensation based on trading and shares held between February 2015 and February 2017. Novo Nordisk, in a letter, announced that it disagrees with these allegations ‘and is prepared to defend the company in this matter.’
The heart of the issues stems from the pricing pressures that the company has been facing for its insulin products in the US. With the shareholders arguing that Novo Nordisk was not transparent about the pricing pressure. A lawyer told Reuters that while the company reported that insulin sales increased from 2015-2017, rebates also sharply rose in this time period.
The US class action suit claim that Novo Nordisk ‘entered to an improper, collusive agreement to increase the prices of their insulin drugs, as evidenced by synchronized skyrocketing prices for the insulin products over the past decade.’ This is in reference to the pricing scandal that hit three of the biggest insulin producers ( Sanofi, Novo Nordisk and Eli Lilly) When the monthly wholesale price of Humulin, the most popular insulin used in type 2 patients, increased to nearly $1,100 between 2010 and 2015, up from $258.
The suit also claims that the company told investors that its profits would continue to increase significantly, even though competitors revealed that their insulin-related products would decline due to the increase in pricing pressures from pharmacy benefit managers.
Novo Nordisk could be in for a tough time as it tries to sort this issue out.
AbbVie won approval in the US for its treatment for moderate to severe arthritis, upadacitnib. The treatment met all its primary and secondary endpoints across its Phase three trial, with the trial evaluating approximately 4,400 patients across all treatment arms in the five studies. According to AbbVie, from the trial results, patients taking upadacitnib achieved clinical remission (when symptoms have lessened to the point that they are mostly absent/gone.) Also good for AbbVie, is that upadacitnib improved outcome in patients with rheumatoid arthritis compared to current blockbuster treatment AbbVie’s own Humira.
This is good news for AbbVie, as Humria has been facing a multitude of biosimilar competition, with rapid losses being experienced in Europe (there was a 17.4% decrease in sales recorded in October 2018.) And with US patent protection ending in 2023, AbbVie needs to have a drug that can offset the losses that will inevitably occur. AbbVie had been banking on its new psoriasis treatment Skyrizi to combat Humira’s decline after it was recently fast-tracked by NICE following European Marketing approval. Following this news, AbbVie’s shares increased by 2%.
The treatment is a JAK inhibitor and this market has recently come under scrutiny with safety concerns surrounding the treatment. As the FDA released new safety data that showed that the drug could increase the risks of blood clots.
The treatment will be available for patients who have had an inadequate response to the current standard rheumatoid arthritis in the US later this month. AbbVie is currently awaiting results from Europe and Japan and if positive results are received upadacitnib could well be on track for reclaiming Humira’s lost ground.
Now that all Q2 results have been released from the big pharma companies, analysts have been able to delve into the data to see which companies have started 2019 with a bang.
There were some surprises with companies like AstraZeneca posting a huge 18% growth, however topping AZ and all the other major pharma companies was Regeneron with an impressive 20% growth attributed to the impressive performance of Eylea, a treatment for chronic eye disorder Wet Macular degeneration. Although impressive that Regeneron topped the table it is important to note that Regeneron had the second lowest total revenues out of the set, so it is easier to post a 20% growth from an initial $2bn compared to the $6bn of the other companies.
Other companies that performed well were Celgene, Alexion, Merck and Bristol Myers Squibb, with each of these companies growing sales in the teen percentage. Prominent swiss companies Roche and Novartis posted Q2 growth results in 9% and 8% respectively. Other major drug companies such as Sanofi and Novo Nordisk posted more modest results of 6% and 4% which is still impressive as they have faced intense pricing pressure.
It was not all positive growth with some companies posting declines. With sales dipping at Allergan, Amgen’s revenue starting to suffer at a multitude of patents cross over at the same time and Teva Pharmaceuticals still struggling with issues that have shares at a 20% all time low.
Teva Pharmaceutical’s CEO has cut 14,000 jobs, shut down manufacturing plants from all around the world in order to save $3bn in costs. However, this is still not enough for debt-rating firm Moody’s and investors.
Moody has revised its outlook of the firm from ‘stable’ to ‘negative’ on the 14th August. Teva’s share prices have not been helped by recent news surrounding the company, with Teva at the center of a generic drug pricing scandal as well as several ongoing opioid lawsuits filed by U.S cities and countries against Teva and other companies. The cumulative affect of these events was enough to drop Teva’s share prices by more than 10%, to $6.30, with Teva’s stock last trading this low back in 1999.
Moody has noted that Teva has more than enough cash to cover the more than $2bn of debt it will mature of the next two years, but that repaying what it owes ‘ will consume a significant portion of the company’s cash and cash flow over the next 18months’ With the firm going on to say ‘Teva will not generate significant cash flow to repay the approximately $4.2bn of debt that matures in 2021.’
There are also further worries that any payments required by Teva pharmaceuticals related to the opioid lawsuits, could divert cash that would be utilized to pay off the debt. Teva has put aside $646million to cover opioid-related expenses, but Moody noted that the amount “represents mainly the current provision for the minimum potential for future liabilities for opioid related cases.” With the figure expected to increase as more information becomes available.
The bad news continues to pile up of Teva, as the revenues from its blockbuster MS drug Copaxone are being rapidly eroded away from a flurry of generics entering the market. And with migraine hopeful Ajovy struggling to pick up the slack from Copaxone, it spells bad news for Teva’s financials.
CEO Schultz has an extremely stressful period ahead of him, during a conference call last week he announced that they have slashed $2.7bn in expenses so far but that it is very likely that the cost cutting will continue once $3bn has been reached. He added that “Teva may need to put into place incremental improvements over time that could involve thousands of different activities and changes.
An ‘express freight service’ for medicinal products will be implemented in the scenario of a no-deal Brexit.
The Department of Health and Social Care announced today that it will set up an ‘express freight service’ to deliver medicines to the UK in the scenario of a medicine shortage in a no-deal Brexit world. It is a service in addition to the extra $2bn the government announced at the beginning of August.
The £25m contract will ensure medicines are still delivered to UK patients and is set to run for 12 months with the possibility of a contract extension. According to the contract details this service will be able to provide, small parcels/packages of medicines or medical products on a 24hour basis, with larger containments available on 2-4-day basis. The government also highlighted that the service will be primarily for standard medicine products but that it will also be able to handle temperature-controlled products if required.
Health Minister Chris Skidmore said that: ‘This express freight service sends a clear message to the public that our plans should ensure supply of medical goods remains uninterrupted as we leave the EU.’
However, amid all this good news, the government is yet to secure a supplier, with the potential bidders having until the 21st August, to submit proposals to win the contract. The successful bidder will be announced in September only a month before the expected 31st October deadline date, leaving no room for mistakes or last-minute decision changes.
This announcement further increases the likelihood of no-deal Brexit scenario and this news has not been taken well by insiders in the Healthcare industry, with many alarmed at what this announcement could allude to in the future. With the British Medical Association (BMA), calling the plan ‘beyond alarming’, with deputy chair of the BMA adding that “ This latest announcement from the government is a further indication of the chaos that will lay in store for the NHS and patients in the event of a no-deal Brexit and highlights just how costly this will be.”
The Association of the British Pharmaceutical Industry reluctantly accepted the news, welcoming the additional measures but stressing that a no-deal should be avoided as not only could it have a dramatic impact on the supply of medicines but that it could also affect ongoing drug research and collaboration with the EU.
Dr Reddy is receiving another regulatory challenge today (after repeated manufacturing setbacks) in the form of an FDA process refusing two of its lucrative generic products. These would be Teva’s Copaxone and Merck’s birth control device NuvaRing.
The company has not revealed where the issues lay in the FDA letter, such as whether the FDA was dissatisfied with the generics or whether it was part of the ongoing manufacturing issue. Dr Reddy has since announced that it will be filing a response to the letter.
This is not a new problem for Dr Reddy, when back in 2015 it received a scathing review/warning of three of its facilities regarding a long list of manufacturing and data irregularities. With one of these facilities being the oncology division, where it continues to this day to struggle with production standards, receiving four Form 483s from the FDA this year alone.
However, there is good news for some as Merck will undoubtedly be pleased, as it lost patent protection for NuvaRing last year and has yet to face generic competition. With the company that makes the first generic set to make a healthy cut, as Merck reported global sales for NuvaRing in 2018 as $902million.
The same cannot be said for Teva pharmaceuticals, where there are multiple generics for Copaxone from Sandoz and Mylan which have been quickly eating away at Copaxone sales to $1.76billion in 2018, a staggering 44% drop from 2017.
Novartis fired top two R&D scientists in-charge of Avexis unit before FDA manipulation data scandal revealed
In early May this year, AveXis’s two top scientists were fired, at around the time that Novartis confirmed internally that the Zolgensama approval application contained data manipulation but, important to note, before it notified the FDA.
These two scientists were former Chief Scientific Officer, Brian Kaspar and his brother Allen Kaspar. They no longer work at Avexis and Novartis has been quick in replacing their roles to a combined position, to be taken over by Page Bouchard, the most recent head of preclinical safety for Novartis institutes for BioMedical Research.
Novartis CEO, Vas Narasimhan, has stated that the company is in the process of eliminating ‘a small number of AveXis scientists.’ According to reports from call data from Novartis, executives were first notified of the data manipulation in mid-March. Then conducted an internal probe in Mid-May before waiting to announce to regulators on the 28th June, a full month after Zolgensama was approved by the FDA.
The CEO went on to say: ‘We need scientists, of course, who follow rigorous procedures and we need leaders who then ensure that there is a strong culture of data integrity and data quality.’
Luckily for Novartis, the FDA have deemed Zolgensama safe and fit for use as manipulation was only implemented towards the animal assay data. Data that was not used in the manufacturing of the commercial product. However, where the issue arises is the process that happened after the data manipulation was revealed internally. With the delay in the notification to the FDA creating questions surrounding Novartis’s conduct and integrity.
Senate Finance Committee Chair Chuck Grassley has started an investigation into the timeline of events that occurred. With Grassley requiring information on who was/will be fired as well as what Novartis will do to stop something like this from happening again.
US politicians have rounded up on three generic pharma companies (Mylan, Heritage Pharmaceuticals and Teva Pharmaceutical Industries) for allegedly stonewalling an earlier effort to gather drug pricing information.
This ‘battle’ has been waged back and forth since 2014, where information was requested by presidential candidate Bernie Sanders among other politicians. The politicians at the time wanted to know why there was a ‘dramatic increase in generic drug prices’ with the politicians claiming there has been multiple follow ups regarding this question.
This probe was reinvigorated when earlier in May this year, Connecticut and 43 other states filed a complaint alleging generic drug manufacturers co-operated to increase the prices of certain drugs, among these lists of drugs were products that were being investigated by Sanders &co back in 2014.
Since this complaint, news has arisen about how the three companies responded to the initial request of information, with an email sent on the 3rd October 2014, from a representative of Mylan Inc to the then CEO of Heritage Pharmaceuticals, Jeffery Glazer, planning a group conference call for their response in order to have all three companies answers on the same page.
The politicians in their demand for information have increased their requests, now also wanting from the companies the same data on sales and expenditures that they sought in 2014 now to be included up to 2018. As well as all three companies providing written company communications related to the 2014 request, as well as documents that identify phone calls that took place between Heritage, Teva and Mylan in the months following the request.
The companies now have until the 28th August to provide this information with Sanders noting that withholding or concealing information from a Congressional investigation is a violation of federal law.
This is not good news for the pharma industry in general particularly for US pharma as pharma companies are repeatedly coming under attack from politicians due to misconduct in these past few weeks. If companies desire the public image of the pharma industry to change, they really have to change their current ideas and actions before relations turn sour with the US government.
US democrat hopefuls Bernie Sanders and Elizabeth Warren have both attacked Novartis over its handling of its gene therapy data.
Zolgensama was thrust into the spotlight last week, when the FDA announced news around the data manipulation that occurred around one of the pre-clinical trials for Zolgensama. To provide a short summary, according to the FDA, AveXis ( the Novartis subsidiary that makes Zolgensama) knew 2 months before approval that data had been manipulated and did not admit to the FDA until one month after approval.
Novartis has since defending itself regarding the allegations, stating that it is still ‘fully confident in the safety, quality and efficacy of Zolgensama’ referencing to how the data manipulation only applies ‘to a small portion of the product testing data’ in relation to the animal subjects and not the humans. With the assays ( activity tests) under scrutiny only being used for product testing and not currently used for commercial product release.
This however has not stopped senators from attacking Novartis, with senators writing “ It is unconscionable that a drug company would provide manipulated data to federal regulators in order to rush its product to market, reap federal perks and charge the highest amount in American history for its medication. Such greed cannot be condoned by the FDA. This scandal smacks of the pharmaceutical industry’s privilege and greed and Americans are sick of it.”
This may seem like a very aggressive attack on an issue that when is analysed in further detail may not warrant such a response, but this ‘attack’ by senators is no doubt further fueled by the price Novartis set for the gene therapy. At $2.1m, the rare disease therapy is the most expensive drug in American history. And as Sanders and the other senators see it, this data manipulation was a result of AveXis rushing to start selling the gene therapy at this price. The senators are annoyed even further due to the US federal support AveXis received for Zolgensama. With the letter going on to further highlight the fast tracking, breakthrough and priority review perks Zolgensama received from the FDA.
The involvement of senators in this issue may result in a situation which Novartis will not be able to brush away so easily, with the senators most likely wanting now to know why the FDA withdrew a proposed regulation covering the prompt reporting of suspected data falsification. It seems Novartis will be in for a tough ride these coming months.
Amgen managed to dodge a big bullet for its top-selling product Enbrel, shaped in the form of Sandoz’s biosimilar Erelzi. Sandoz said it will appeal the decision but for now Erelzi will be kept of the market, embarrassingly for Sandoz this could delay the launch for at least a decade after receiving FDA approval in 2016 and executives praising the ‘soon to be roll out of the product’ stating that it could be rolled out as soon as next year.
This is a huge win for Amgen, as it will potentially save them multi-billions as Enbrel was approved back in 1998 and last year brought in sales of $4.8billion, which accounted for more than a fifth of the companies’ top line.
Sadly, this news is a recurring theme for the biosimilar industry in the US, with many biosim makers complaining that biologic drugs are often protected by ‘patent thickets’ which makes it incredibly hard for them to launch copycats. And once they reach the US market, they face further challenges in the form of companies like J&J developing strategies to combat against biosimilar competition such as striking “exclusionary contracts.”
This is not an issue faced in Europe where copycat biologics are faring much better, with AbbVie’s huge blockbuster facing a variety of biosimilar competition. The US markets response to the growing industry of biosimilars has come under fire many a time particularly by former FDA chief Scott Gottlieb who blasted drug makers for the ‘anemic’ market. The FDA has promised to act but many of the hurdles that biosim face fall outside of its jurisdiction. And with Gottlieb stepping down last year, it remains to be seen the priority that the FDA will place on this issue.
Amgen has managed to dodge the bullet for Enbrel but many of its other drugs including; Neulasta, Epogen and Sensipar have given ground to generics. Ironically, Amgen’s biosimilar division is set too boom with analysts from Cantor Fitzgerald forecasting $2.8billion in sales from Amgen biosimilars.
Results from the newly updated FLAURA trial show that Tagrisso extends survival in previously untreated patients with EGFR-positive non-small cell lung cancer, building on the 2017 results and helping AZ in heading towards AZ target of increasing its use in a first line setting.
Its results surpassed AZ’s own Iressa and Roche’s Tarceva and according to the head of oncology at AZ, Jose Baselga, it is the only medicine to do so. He stated that it provides an ‘unprecedented survival outcome versus previous standard of care inhibitors’ and that it should be the ‘new standard of therapy for non-small cell lung cancer.’
It was necessary for AZ to perform further trials as the data from the 2017 FLAURA trial did show a trend of increasing the OS but the earlier readouts were too immature to show statistical significance. This new data will be welcomed by AZ officers, as it will help to set apart Tagrisso in the EFGR-inhibitor category, a category which is becoming increasing competitive, with Pfizer’s Vizimpro set to jostle its way in.
This data will no doubt be used by AZ to appeal against NICE ( UK cost-effectiveness body), after it turned down Tagrisso as a first line EGFR-positive Non small Cell Lung Cancer (NSCLC) treatment, in part to the original OS data from the 2017 trial being inconclusive when compared too older, cheaper rivals. NICE also decided at that time that Tagrisso would not be included in the Cancer Drugs Fund, citing it was too expensive and instead recommended Pfizer’s Vizimpro for routine use in the NHS.
Tagrisso is already dominating as a second line use for NSCLC, with AZ doubling its efforts to get more approvals for it as a first line treatment. The successes of Tagrisso are reflected in AZ quarterly earning reports, with Tagrisso being AZ top selling product, will sales doubling to $1.4bn and forecasted to reach $3bn by the end of this year.
Continuing the new series where I cover aspects of the industry over the weekend, in this post I will
be covering the life cycle of products in the pharmaceutical industry.
be covering the life cycle of products in the pharmaceutical industry.
Pharmaceutical life cycle management is the process of managing the entire life cycle of a drug including its research, design and manufacture, service and disposal. Companies utilise it to maximize sales throughout their products life cycle and it provides an extra competitive edge, increasing profits.
Its critical that companies have an efficient product life cycle management due to the significant capital and resources injected into R&D and regulatory approval subsequent profits would take years to produce. And with a relatively small period in which companies can sell without generic competition, it is essential that companies can maximize their products lifetime value.
Drugs life cycle can be split into three stages, an extensive early development period, a highly competitive mid-life period and a significant late post-patent period. Unlike most products, drugs have a lengthy closely regulated and complex developmental pre-marketing phase usually lasting a decade or longer.
The first and most lengthy stage is the development stage and regulatory approval. It is the most expensive out of the three with drug discovery, identification of candidate, non-clinical testing on animals and safety and efficacy tests performed first to identify and make a product that can be used on the human population. Once the pre-clinical tests have been fulfilled it will go onto the clinical trials which are split into three phases.
Phase 1, tests on a group of healthy volunteers (20-100) where small doses of the product will be administered where they are closely supervised, this stage can approximately last for several months and its purpose is to investigate safety and dosage.
Phase 2, tests approximately 50-100 patients with the disease and lasts from several months to two years. The purpose of stage two is to investigate the efficacy of the drug and its potential side effects. Most drugs fail at this stage showing detrimental side effects and only 33% of drugs past on to the final stage.
The final phase trial tests a much larger population of patients, often 1000-5000 across international sites. The purpose of this stage is to confirm the phase two trial results but on a much larger scale.
After the pre and clinical trials, all the data accumulated needs to be submitted in appropriate forms to the regulatory authorities along with quality of the data and the description of the manufacturing process for review. The drug is only approved if regulators can find proof from the data of its quality, efficacy and safety.
Preclinical development can take between one and six years, while the clinical development stage can take between just over 6 months and two years. This shows how lengthy and costly this stage is and it is without guaranteed success thus further highlighting the need to maximize the drugs life cycle while it still has a patent. Pharma companies have been looking into reducing the development stage to reduce development costs and to increase the period of market exclusivity that the drug enjoys. Companies have been looking into this by utilising new technology such as 3d imaging and AI, with the latter being able to sift through vast amounts of data to identify target molecules, shortening down the process from years to a few months.
The next stage in the life cycle is the market-exclusivity stage, this stage is designed to increase innovation and investment in the industry by protecting new products from competition. A patent can be filed at any time during the development stage, which means that if a drug has a very length development process, it is possible that it could reach the market with a very limited amount of patent protection remaining. To create a balance between innovation and greater access to drugs, the FDA awarded an extra 5 years of exclusivity following a successful new chemical entity application. In this phase, this is where companies attempt to recoup development costs and generate profit. It can be split into three smaller stages of 1) Introduction 2) Growth and maturity and 3) Decline
1) Introduction- is the phase that covers product launch, distribution arrangements are introduced and there is typically large expenditure spent on promotion and advertising.
2)Growth and Maturity- This the successful phase in the life cycle and the perfect opportunity for companies too focus on increasing market share. In this stage, product availability and services are improved. In the maturity phase, this is when variations of the main product saturate the market. This phase is the perfect time to increase the products life span, which is achieved by changes in pricing and discount policies. As well as the scope of promotion altering from getting new customers to product differentiation in terms of quality and reliability.
3)Decline phase- Is the time variations of the product that are weak are withdrawn from the market but prices of the main product are still competitive and promotion is only withdrawn to a level that will keep the products presence visible.
The final stage of the life cycle is post patent expiration. Companies in this period rather than trying to compete against the generics they try to extend the patent. There are several strategies which companies implement including claiming delays occurred during the initial application process both with the patent office and FDA or applying for a new formulation patent.
Product Life Cycle Management is extremely important for companies to implement and with its relevance becoming ever increasingly important due to a serious decline in research and development productivity, companies need to be able to maximize the efficiency their products.
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