Novo stock shrugs off FDA probe

The U.S. FDA communicated on Thursday that it is investigating some findings suggesting increased risk pancreatitis and findings of pre-cancerous cells of the pancreas related to incretin mimetic drugs for type 2 diabetes. These include Novo Nordisk’s (OMX: NOVO B) blockbuster Victoza (liraglutide) among a host of other products. The markets did not seem overly concerned and Novo fell only slightly on the news this week. There is a large array of studies and data available on the matter regarding the GLP-1 agonist, with many finding no such links as well and even as we speak, prescriptions of the drug should involve a risk-benefit analysis. An entirely different matter is that all of these concerns may make it more tenuous to gain an approval in obesity space.

FDA ask additional cardiovascular data for Tresiba and Ryzodeg

Novo Nordisk (OMX: NOVO B) announced tonight that it has received a complete response letter from the US Food and Drug Administration pertaining to the NDA of insulin degludec (Tresiba®) and insulin degludec/insulin aspart (Ryzodeg®). The company is asked to deliver additional data from a dedicated trial looking into cardiovascular outcomes.

Novo expressed disappointment and surprise and says it will not be able to provide such data within 2013. It is now evaluating the response and will work with the agency regarding the path forward. The products are approved in various locations such as EU and Japan. Novo will host a conference call tomorrow at 8 AM CET on this clearly material setback.

FDA advisory committee text on Tresiba sinks Novo

Novo Nordisk’s (OMX: NOVO B) seemingly unwavering march toward 1000 DKK hit a severe speed bump today. The Danish firm had an all-time high close of 970,50 DKK to end the previous week upon announcing that European regulatory authorities gave a positive opinion on insulin degludec and insulin degludec/insulin aspart once-daily basal insulins (to be known commercially as Tresiba and Ryzodeg). The drugs are expected to compete with the blockbuster Insulin glargine (Lantus) from Sanofi-Aventis (Euronext: SAN, NYSE: SNY, FWB: SNW).

Today Novo was under severe pressure due to a stock exchange notice released after market close on Thursday pointing to a recently published U.S. FDA document relating to an upcoming advisory panel meeting. The document in question was a waiver for a suggested participant so its main purpose was not to disclose information about the topics that are to be covered; those are likely to be released closer to the scheduled date of November 8, but in it was said that meta-analysis of several clinical trials suggests an excess risk for cardiovascular events over comparators. It was also noted there may be a benefit from lower risk of hypoglycaemia than the comparator insulin. Novo Nordisk has previously maintained that the lower risk of nocturnal hypoglycaemia would be the differentiating factor with the competitor while efficacy seems comparable.

Documents brought forward before an advisory panel meeting tend to try to include all the potential major issues to be discussed and sometimes appear more serious for the prospects for an approval than they actually are, but cardiovascular concerns particularly following the well known Avandia case are such that no panellist wants to be blamed for supporting a drug that turns out to have such concerns after the fact. Therefore there is a definite additional uncertainty over approval. The big question is if the panel and later the FDA will opinionate for the need of a cardiovascular study before commercial approval, after it or not at all. The FDA had previously asked for an extension into the review period for Tresiba.

Novo: FDA decision on degludec delayed

Novo Nordisk (OMX: NOVO B) said that the U.S. FDA has tentatively scheduled an Advisory Committee meeting to discuss the NDA for the ultra-long-acting insulin degludec and insulin degludec/insulin aspart on November 8th 2012. This delay was a disappointment for the market, where hopes of a direct path into approval decision had been raised. There hasn’t been any communication regarding a new action date. The stock which boasts highest market cap in the Nordic exchanges is down 1% in early afternoon session.

A target price hike has helped Novo in today’s trading somewhat. The FDA approval of another obesity drug in Qnexa, that will be marketed as Qsymia, from Vivus (NASDAQ: VVUS)however should not have had any particular effect on Novo at this point when it was already clear earlier, that drugs can be approved in this space after all.

AstraZeneca Bristol-Myers Squibb diabetes alliance widens as the latter makes recommended offer for Amylin

Bristol-Myers Squibb Co (NYSE: BMY), has agreed to buy biotechnology company Amylin Pharmaceuticals Inc (NASDAQ: AMLN) 5.3 billion USD in cash on a debt-free basis. The total value of the transaction after taking into account Amylin’s net debt and contractual obligations to Eli Lilly and Company (NYSE: LLY) is about 7 billion. Soon after the announcement, it was said that AstraZeneca (LSE: AZN, OMX: AZN), which had been thought to be in the running to buy Amylin and Bristol-Myers have made a deal to collaborate on Amylin’s products with AstraZeneca paying Amylin, as then a wholly owned Bristol-Myers subsidiary, 3.4 billion in cash for the rights upon the completion of the acquisition. This builds on top of earlier diabetes treatment cooperation of the two big pharma companies.

Bristol-Myers and AstraZeneca will share the profits and losses from the collaboration equally. The Boards of the three companies have approved the deals. AstraZeneca expects immediate positive impact on revenues as it seeks to add into its thin patented drugs and late-stage pipeline. Amylin’s portfolio of GLP-1 drugs including Byetta and Bydureon competes among others with Novo Nordisk (OMX: NOVO B). Added muscle behind the drugs should make the alliance an even more formidable competitor. Amylin’s other assets include a leptin analog Metreleptin currently under FDA review and approved amylin analog SYMLIN® (pramlintide acetate).

Weight loss drug approval helps Novo too

Two important decisions in the United States helped Novo Nordisk (OMX: NOVO B) to a solid gain yesterday. The first obesity-drug approval in a great while in Arena Pharmaceutical’s (NASDAQ: ARNA) lorcaserin, which will be marketed as Belviq, the previous night pushed the likelihood in investors minds that Novo’s type-2 diabetes approved Victoza will one day be approved for the purpose as well. While effective weight-loss drugs might eat away from future diabetes-related sales, that is obviously not a concern in any way, and lorcaserin for one hasn’t shown any compelling efficacy.

Other approval decisions in the field are due in the near future with Vivus Inc. (NASDAQ: VVUS) and Orexigen Therapeutics (NASDAQ: OREX , FRA: JXS) hoping for a similar ruling. Yesterday’s almost too close to call ruling by the Supreme Court to uphold the so-called ObamaCare was an event that was probably going to be considered positive either way. With the decision to keep it in place as it is, certain uncertainty is removed concerning pharmaceutical companies, even if businesses are confused on the real effects of the mammoth of a Law.

Novo chooses semaglutide as its once-weekly GLP-1 drug candidate

Novo Nordisk (OMX: NOVO B) will take its once-weekly GLP-1 analogue product candidate semaglutide into phase 3 development in type 2 diabetes. Novo had been contemplating wether to study 1 week formulation of its blockbuster Victoza (liraglutide) or semaglutide in the program after competitors have been bringing their long-lasting drug formulation lessening the need of injections into market. Novo has now concluded that semaglutitde has a more attractive profile for once-weekly administration (a longer intrinsic circulation half-life). Therefore no further clinical activities with once-weekly version of liraglutide are expected.

The company says that clinical data from earlier semaglutide trials shows promise for a differentiated profile and improvement to the treatment in terms of glucose control, weight loss and a low level of hypoglycaemic events after weekly dosing. The global clinical development programme SUSTAIN is expected to start in H1 2013 and include more than 8000 patients. Novo’s share is hardly affected by the news in early trading.

Diabetes stocks in focus

With the 72nd Scientific Sessions of the American Diabetes Association or ADA 2012 ongoing in Philadelphia, pharmaceutical companies involved in this fashionable space are under investor gaze this morning. Novo Nordisk (OMX: NOVO B) is involved in plenty of the talk and comparison studies. Its long-acting insulin analogue Levemir was compared to Amylin Pharmaceuticals’ and Alkermes’ once-weekly glucagon-like peptide-1 (GLP-1) receptor agonist Bydureon in a small clinical study initiated by the American companies and they reported that their drug showed greater glucose control, weight loss and lower risk of Hypoglycemia in type 2 diabetes patients. Novo’s representatives view the study as lacking in scientific basis, with the dozing regime of Levemir and other such matters not becoming evident from the data. Earlier Bydureon had been compared to Novo’s Victoza, which is a drug similar to Bydureon and a more direct competitor, and in this study Novo’s drug performed better.

Novo on its behalf reported data comparing its Investigational ultra-long-acting insulin degludec or Tresiba against long-acting basal insulin analogue insulin glargine or Lantus, which is a blockbuster market leader drug from rival Sanofi-Aventis (Euronext: SAN, NYSE: SNY, FWB: SNW) indicated for both type 1 and type 2 diabetes with nearly 4 billion Euros in sales last year. Novo said that Tresiba significantly reduced rates of nocturnal (night-time) hypoglycaemia in type 2 diabetes patients versus insulin glargine while showing equal improvement in glucose control in a 52-week Phase 3a study. Sanofi naturally was less convinced by the data, saying its own readings on Lantus hardly match those shown in Novo’s study. The U.S. FDA recently lengthened the review period for Tresiba for an additional three months.

Sanofi also presented plenty of data (altogether 17 abstracts) on its GLP-1 drug candidate for type 2 Diabetes mellitus called Lyxumia or Lixisenatide, which was in-licensed from another Danish company called Zealand Pharma A/S (CPH: ZEAL). Sanofi also said this morning, that it has submitted an application for the regulatory approval of the drug to the Ministry of Health, Labour and Welfare in Japan. The application follows similar action in Europe based on the over 5000 patients treated in GetGoal Phase III clinical trial program. Sanofi and Zealand Pharma also highlighted early-stage animal data from a GLP-1-gastrin dual agonist peptide called ZP3022.

NOVO: FDA extends degludec and insulin degludec/insulin aspart review period

Novo Nordisk (OMX: NOVO B) said this morning that the U.S. FDA has extended the regulatory review period for Novo’s new drug applications (NDA) for the two insulins degludec and insulin degludec/insulin aspart intended for the treatment of type 1 and type 2 diabetes. The agency says it requires more time to complete its review after previously asking for more data and analyses. Novo says it has submitted plenty and the agency considers those a major amendment(s) to the NDA(s).

Insuling deglugec is a once-daily ultra-long acting basal insulin analogue and Insulin degludec/insulin aspart contains the former in a formulation with a boost of insuling aspart, combining the long-acting insulin and rapid acting insulin. There are also pending applications in Europe for two products. No request for additional clinical trial has been made. The new action date is 29th of October 2012.

Amylin offers reportedly coming in, AstraZeneca still in the mix

The bidding for Amylin Pharmaceuticals (NASDAQ: AMLN) seems to be heating up. The Telegraph reported during the weekend, that AstraZeneca (LSE: AZN, OMX: AZN) had apparently made a takeover bid valuing the company over 4 billion USD, following a rejected offer of 3.5 billion from Bristol Myers Squibb. Bloomberg now writes that several companies are still in the running, with AstraZeneca likely the most desperate of those.

Investors Carl Icahn has been pressing Amylin to complete a deal, something to which it was initially averse to. A second round of bidding is believed to follow soon, with a decision in place perhaps next month. Cowen & Co analyst Phil Nadeau told Bloomberg, that Amylin may generate up to 1.5 billion USD in annual sales from Diabetes treatments Byetta and Bydureon that compate with drugs from Novo Nordisk (OMX: NOVO B)

Novo Nordisk slides after Q1 report as Victoza sales raise some questions

It has been a while since Novo Nordisk (OMX: NOVO B) has disappointed investors. Since the share is trading with such a high multiple, any perceived miss will have a pronounced impact. Therefore it is not a major shock that today's interim report led to a three percent decline, even though the negative issues in the report are at the very least debatable. First quarter sales of 17 551 000 000 DKK is 13% more than last year but a 2% decline sequentially. Healthcare reforms explain much of that.

Operating profit grew close to 6.4 billion as operating margin improved to 36% from 33-34% range maintained for the entire last year. The company reported diluted earnings per share of 8.32 DKK (about 1.48$ for ADR share holders). Outlook for 2012 was adjusted slightly in a number of points. The overall effect of those seems slightly positive.

First quarter sales of Victoza were just under 2 billion DKK, which while being 81% more than on Q1 2011, are 5% less than on Q4 2011. The company attributes that to rebate reversals and normal seasonality. So far Victoza is holding competitors at bay. The global market share of Victoza in the GLP-1 segment was 62% vs. 58% during Q4 2011. The GLP-1 class value share of total diabetes care market increased to 4.8%.

Modern insulins NovoRapid, NovoMix mix and Levemir reported sales were pretty much on par with Q4 2011 and up 17% year-on-year at 7.87 billion. Human insulin sales were stable around 2.7 billion. Novo Nordisk now commands half of the total insulin market and a quarter of global diabetes care market, which continues to grow high single digits annually.

Novo has new products approaching market as well. Tresiba and Ryzodeg regulatory reviews continue. Victoza cardiovascular outcomes trial, which could potentially go towards obesity indication too, has now completed enrolment. Phase 3 programme for long-acting recombinant factor VIII compound, N8-GP for haemophilia A treatment was initiated. The lone negative pipeline news related to anti-NKG2D in rheumatoid arthritis, which did not show a treatment effect on the disease in Phase 2a trial.

The current Chairman of the Board Sten Scheibye is joining the Board of Novo Nordisk Foundation and is set to become its chairman in 2013. Therefore Novo Nordisk expects to elect a new chairman next year. The Board expects to propose current vice chairman Dr Göran Ando for the job. The company also said it plans to hire more people in the United States as the company plans to add nearly 15% or close to 600 people more to its workforce in the country.

Novo’s Prandin patent submission may be challenged

Novo Nordisk A/S (OMX: NOVO B) said after market close on Tuesday that the US Supreme Court reversed a Court of Appeals ruling from 2010 on generic drug maker Caraco Pharmaceutical’s right to challenge Novo’s patent submissions for type 2 Diabetes drug Prandin (repaglinide). The Appeals Court ruling had earlier reversed a District Court for Caraco’s and a separate appeal at The Court of Appeals is pending.

Novo has a method-of-use patents for the compound in combination treatment with generic antidiabetic drug metformin still valid for several years while the patent for repaglinide expired in 2009 . The drug is approved for three different uses and Caraco wants to manufacture it for the other two unpatented uses, something that the US Congress has recently made possible.

The issue has to do with earlier finding that pharmaceutical companies may sometimes submit incorrect patent information to the FDA. The Supreme Court ruled that generic drug makers can challenge how branded drug patents are described. This will have wider implications on how pharma will have to word their NDA filings; with more clarity and less wide ambiquity.

Novo Nordisk maintains that its patent filing is correct. US Sales of Prandin and repaglinide/metformin tablet marketed as PrandiMet were approximately 1 billion DKK (~ 176 million USD) in 2011. Novo Nordisk's share closed at all time high levels of 854 DKK for the day.

Novo overtakes Statoil as exchanges prepare for Easter

Nordic exchanges are heading for Easter holidays. Oslo already closed earlier today and Copenhagen will join it on the sidelines tomorrow. Stockholm will be open for half a day and only Helsinki has a normal trading day. Investors have been taking profits and a wobbly debt auction from Spain escalated the slide on Wednesday.

Generally there were very few company specific news. One tidbit is that Novo Nordisk has overtaken Statoil as the largest listed company in the Nordic countries, with both hovering around 65 billion Euro market cap. Various subsidy cuts across the world have really hit solar (Renewable Energy Corporation) and wind (Vestas, which also has had to digest other negative news) sectors.

Novo up as advisory panel vote concerns subside

A U.S. FDA advisory panel voted last Thursday that the agency should ask for more cardiovascular data before the approval of treatments for obesity. Cardiovascular concerns have delayed or even thwarted many companies seeking to develop treatments for overweight people. Only recently there have been some signs that the agency may be open to an approval in this space.

The vote weighed on Novo Nordisk (OMX: NOVO B) on Friday as its Victoza (Liraglutide) is a treatment candidate for this condition. On Monday Novo played down those concerns, saying that its data set from Diabetes trials could be leveraged in obesity filings.

Early numbers also suggest that Novo has defended Victoza’s market share successfully against recently marketed long-acting competitor Bydureon in type 2 Diabetes. Novo also seems to be more open than before on gunning for a once-weekly drug of its own as well. On Monday the stock shot up more than 5% to once again approach record levels.

AstraZeneca looking to do several smaller deals

AstraZeneca (LSE: AZN, OMXS: AZN, NYSE: AZN) recently lowered its guidance for pipeline contribution into future revenues. Particularly the failure of Targacept in-licensed major depressive disorder drug candidate TC-5214 to reach primary endpoint in two Phase 3 studies was a major blow. The company seems to be ready to try to address its bleak future revenue outlook with external growth.

Reuters interviewed R&D President Martin Mackay who admitted that they are talking to a number of companies for various deals. Last major move was a 15.6 billion USD deal for MedImmune in 2007, which has failed to live up to expectations. This time the company looks poised to do a series of smaller (”low billions”) deals instead. This could include both acquisitions and in-licensing of drugs.

Bernstein analyst Tim Anderson is one of many to throw the name of Amylin Pharmaceuticals (NASDAQ:AMLN) into the mix as a potential target. A standard 30% premium would still leave the price tag below 5 billion. Nordic investors are already keeping Amylin on their radar as its newly approved type 2 diabetes drug Bydureon is set to compete against Novo Nordisk’s (OMX: NOVO B) Victoza. Reuters asked Mackay about Amylin, who merely said that GLP-1 diabetes drugs are an interesting class.

First in a series of large patent expirations that the Anglo-Swedish company is staring at is only weeks away as schizophrenia, bipolar disorder and add-on depression drug Seroquel (quetiapine), which grossed, almost 6 billion USD last year taking into account both once-daily and twice-daily formulation, is set to come off-patent this month in the United States and Europe (U.S. patent expiration date is March 26th 2012). The sustained-release version appears to maintain exclusivity until 2017, leaving the company with some advantages over generic competition.

Novo Nordisk expects rapid sales growth to continue in 2012

Novo Nordisk (OMX: NOVO B) reported its Q4 2011 and full-year numbers this morning. In 2011 operating profit grew by 18% and sales by 9%. Diluted 2011 earnings per share were 29.99 DKK. Fourth quarter was by far the strongest of the year with over 18 billion DKK sales and over 6 billion operating profit.

Novo’s board is suggesting a dividend of 14 DKK for 2011, which is a 40% hike on 2010. Novo Nordisk concluded its 2011-2012 12-month share repurchase programme with the purchase of over 18 million shares. The company plans to cancel 20 millon B shares representing 3.4% of the total share capital. The board has also approved a new 12 month share repurchase programme of DKK 12 billion.

Victoza sales in 2011 were 5.991 billion DKK (USD 1.06 billion). The sequantial growth escalated to 35% in Q4. The competitive landscape will change going forward with the approval of Bydureon just days ago. Novo’s President & CEO Lars Rebien Sørensen commented to the press that he expects interesting competition that may expand the market but did not sound too worried.

US FDA also recently approved another drug called Jentadueto (linagliptin/metformin hydrochloride) from Boehringer Ingelheim Pharmaceuticals, Inc. and Eli Lilly (the two companies have formed a ”worldwide diabetes alliance”), for type 2 diabetes, but this drug is seen more as a part of a treatment regime.

Approximately 10% growth in modern insulin analogues NovoRapid and Levemir continued as well. Modern insulins is still by far the highest selling business segment with 7.8 billion DKK (over 1 billion Euros) in Q4 sales.

As far as new product candidates are concerned, regulatory review for ultra-long acting insulins Degludec and DegludecPlu are progressing with US regulatory action date being 29.7.2012 and European review ongoing as well. Phase 3a trial with turoctocog alfa, which is a recombinant FVIII for treatment of haemophilia A, has been completed and Novo plans to file for marketing authorization in H2 2012.

Novo is guiding for 9% sales growth in DKK to continue in 2012 with 7-11% growth in local currencies. Operating growth is expected to be around 10%. The stock is showing strength and is still up by 4% for the day well above 700 DKK a share.

Novo’s competitor gets an approval for type 2 diabetes drug

Novo Nordisk (OMX: NOVO B) could be under some pressure on Monday as Amylin Pharmaceuticals and Alkermes, Inc could announce on Friday after European markets had already closed that the US FDA finally approved type 2 diabetes drug Bydureon. The FDA had rejected the drug twice demanding more data where as EMA already approved the drug in 2011. Bydureon, which is long-acting release formula of Byetta (exenatide) will go compete against Novo’s blockbuster drug Victoza (liraglutitide).

Victoza has managed to gain market share from Byetta on active marketing supported by favourable data comparison from LEAD-6 clinical trial. However, Byetta has been enjoying some tier advantages in the US and it had been holding on somewhat better than expected. All of the drugs mentioned here belong to a class called glucagon-like-peptide-1 GLP-1 (which is an incretin) receptor agonists.

Victoza, is injected daily where as Byetta on which Bydureon is based is injected twice a day. Presumably the main advantage that Bydureon will have is that it only needs to be administered once a week, a fact made possible by Alkermes’ proprietary technology for controlled release of medications. Efficacy will still be a selling point for Novo’s drug as studies conducted so far compare Victoza’s blood sugar level control favourably to that of Bydureon’s. Each injection of Bydureon is also more cumberrsome and done with a larger needle than an injection of Victoza.

Victoza sells well north of a billion U.S dollars at the moment, with around half of that coming from the United States. Analysts’ predict that Bydureon will eventually reach blockbuster status as well and its approval this time was expected. Bydureon will carry a warning on pancreatitis and possible elevated risk on a certain type of thyroid cancer risk. Victoza also carries a warning on similar issues. Both drugs are indicated as an adjunct to diet and exercise. Novo Nordisk will report quarterly earnings next Thursday.

Novo Nordisk tops clean capitalism list

Nordic companies are clearly overrepresented in Corporate Knights 8th annual ranking of the most sustainable companies in the world. Danish pharmaceutical company Novo Nordisk (OMX: NOVO B) was chosen as the most sustainable company by a wide margin. Last year Novo was down in 16th place. It scored particularly well in this study in energy productivity and in CEO vs. average employee compensation.

The idea of the list is to find companies who not only act in the interests of the business but also for the entire planet in doing so. That means that companies fully take social, economic and ecological costs and benefits into account. A situation where a company’s private optimum level of production differs from the social optimum due to externalities is one type of market failure, which is not normally addressed on the corporate level.

Other Nordic companies close to the top are oil producer Statoil ASA (OSE:STL) at number 3 and Danish biotech company Novozymes A/S (OMX: NZYM B) at number four. Aluminium producer Norsk Hydro ASA (OSE: NHY) and Swedish industrial group Atlas Copco (OMX: ATCO A, ATCO B)) round up the top ten.

Below the top ten one can also find Swedish telecom company TeliaSonera (OMX: TLSN, OMXH: TLS1V) at 13, oft-maligned oil refining and marketing company Neste Oil Oyj (OMX: NES1V) from Finland at 19, Danish wind turbine manufacturer Vestas Wind Systems A/S (OMX: VWS) at number 31, Swedish heavy trucks and buses manufacturer Scania AB (OMX: SCV B) at 36, Reverse vending machines firm Tomra Systems ASA (OSE: TOM) at number 39, Finnish retailing conglomerate Kesko Oyj (OMX: KESB) at 43, Norwegian financial services company StoreBrand ASA (OSE: STB) at 54, Swedish retail-clothing giant H & M Hennes & Mauritz AB (STO:HM B) at 67 and Danish medical devices firm Coloplast A/S (OMX: COLO B) on 84th place.

Good quarter for Novo Nordisk

Danish Big pharma company Novo Nordisk (OMX: NOVO B, NYSE: NVO) delivered a strong set of numbers. Q2 sales were 16 billion DKK and operating profit 5.265 billion. Operating margin was down slightly towards Q1 but financial items pushed net profit to slightly higher at 4.134 billion.

Sales growth was spurred by (GLP-1) analog Victoza® [Liraglutide (NN2211)], and the insulin analogues (insulin detemir )NovoRapid® and (insulin aspart) Levemir®. Victoza sales grew by 253% to 2.348 billion DKK for the first six months of the year.

Novo has started several new phase 3 programs. The outlook for 2011 was raised. Sales growth is now expected to be 9-11% (8-10%) and operating profit to be 15-19% (~15%). The stock is up around 2%. Full report is here.