Pharmaceutical News

LogiPharma 2012

The 11th annual LogiPharma Europe 2012 is the only end-to-end life science supply chain conference where over 300 strategic-level pharma, generics and biotech professionals meet to benchmark, network, share best practices and assess latest industry approaches to optimising supply chain performance and security.

To register your interest or to download a brochure, please vist the LogiPharma website by clicking on either of the banners below, thank you.

Date: 04/24/2012 – 04/26/2012

Location: Geneva, Switzerland

Organiser: Worldwide Business Research Limited

Phone:  +44 (0)20 7368 9465
Fax: + 44 (0) 20 7368 940
Email: logipharma@wbr.co.uk
URL: http://www.logipharmaeurope.com
Contact: Samantha McCarthy

Government announces boost for local pharmaceutical sector

An interesting article from Espicom’s  World Generic Markets business publication.

On 13th April 2012, South Africa’s Department of Trade and Industry and Department of Health jointly announced the designation of certain pharmaceutical products for domestic production.  The government bodies commented that the designation was in line with the amended Regulations to the Preferential Procurement Policy Framework Act (PPPFA), which were promulgated in 2011 and make provision for designation by the Department of Trade and Industry of sectors, sub-sectors and industries identified in national economic development and industrial policies, for the procurement exclusively from domestic manufacturers.

The departments commented that South Africa has one of the worst disease burdens; consequently, it is important to ensure supply security and development of local capacity.  The designation of the pharmaceutical products would thus benefit the country both in terms of health and economy.  The designation includes the oral solid dosage tender worth over R2.5 billion (US$318.3 million) over two years.  The potential list of more than 70 pharmaceutical products is being finalised.

The intention behind the announcement is to create security of demand for domestic production, attract foreign and domestic investment and to further industrialise South Africa’s economy.  The Trade and Industry Minister, Dr Rob Davies, noted that the pharmaceutical sector is the fifth largest contributor to South Africa’s import burden, and commented that reversing this was an important challenge, whilst still ensuring that affordable healthcare is available to the public and private sectors.

According to Dr Davies, prices will be benchmarked internationally and local manufacturers will have to ensure that the benchmark is not exceeded to quality, thus ensuring that medicine prices remain affordable.  The minister added that for security of supply purposes, the government would still continue to source some of its medicines from importers.

Commenting on the announcement, Adcock Ingram said that it welcomed the move.  The firm commented that it took the view that a greater alignment between industrial policy and government procurement was critical for ensuring a sustainable pharmaceutical manufacturing base in South Africa.  Adcock argued that the move would also have a significant effect on patient access to affordable medicines.  In addition, as the local manufacturing base grows through increased capacity utilisation and the attainment of economies of scale, so South African manufacturers would be well placed for global competition and export potential.

Article source: Ian Platts. Editor of Espicom’s business publication World Generic Markets

Mark Dreyfus Announces Intellectual Property Laws Amendment Bill

I hope you have all had a good week, here is the last in this weeks articles from Espicom’s World Generic Markets business publication, please read on…

On 20th March 2012, Mark Dreyfus, Parliamentary Secretary for Industry and Innovation, announced that Australia’s intellectual property system would be amended through the Intellectual Property Laws Amendment (Raising the Bar) Bill, which was passed by Parliament.  The MP explained that the amendment would provide a timely overhaul of Australia’s intellectual property system and would build on the R&D Tax Incentive introduced in 2011 to support the transition to a knowledge economy.  Mr Dreyfus commented, “Researchers will benefit from certainty that they can explore new ideas free from the threat of patent infringement.”  Raising the Bar addresses six key areas:

• Raising the quality of granted patents: the new standards will be more closely aligned with international standards;

• Free access to patented inventions for regulatory approvals and research: ensuring experimentation and approval for generic manufacturers is not delayed or negatively impacted by patents;

• Reducing delays in resolution of patent and trade mark applications: the Act tightens up the procedures for patent and trade mark oppositions and patent divisional applications;

• Assisting the operations of the intellectual property profession: the Act allows Australian patent and trade marks attorneys to incorporate, giving them greater freedom in their business;

• Improving mechanisms for trade mark and copyright enforcement: the Act increases the penalties for trademark infringement bringing the Australian system into line with the country’s major trading partners;

• Simplifying the intellectual property system: the Act gets rid of unnecessary hurdles and simplifies the application process.

Commenting on the amendments, Australia’s Generic Medicines Industry Association (GMiA) said that it welcomed the changes.  The organisation noted that the legislation would enable Australia to better meet the objectives of the intellectual property rights system to support innovation by encouraging investment in research and technology in Australia and by helping Australian businesses to benefit from their ideas.  The organisation commented that the existing patentability standards in Australia were set at a level lower than the standards set in other countries which make up the country’s major trading partners.  The existing balance, the GMiA argued, was not in the public’s best interests.  Patents that have been invalidated in other jurisdictions continued to work in Australia, resulting in higher prices for the Australian public.  Local researchers are disadvantaged by the broader reach of Australian patents.  The organisation added that the granting of weak patents restricted innovation, competition and diffusion of knowledge, and also added unnecessarily to costs to the public.

The legislation passed into law with the Governor General’s assent on 15th April 2012.  Most of the provisions in the Act will come into effect on 15th April 2013; however, some changes apply immediately.

Article source: Ian Platts. Editor of Espicom’s business publication World Generic Markets

World Generic Markets Update

On 26th March 2012, Senator Patrick Leahy (D-Vt) announced that he was introducing legislation to the Senate with the aim of reversing a recent Supreme Court decision which the senator claimed threatens the safety of consumers taking generic drugs.  The senator explained that in a 5-4 decision in 2011, the Supreme Court had held that state law tort claims against generic manufacturers are pre-empted by federal laws, which requires generic drug manufacturers to use the same label as a branded drug, even when the generic manufacturer knows that the warning on the label is inadequate.  The litigation the senator was referring to was the case, Pliva vs. Gladys Mensing, together with Actavis Elizabeth vs. Gladys Mensing and Actavis vs. Julie Demahy.  The cases had centred on the drug metoclopramide, marketed by Alaven Pharmaceuticals under the brand name Reglan, but also produced by generic firms including Actavis, Pliva’s owner, Teva Pharmaceutical Industries, Ipca Laboratories, Northstar Healthcare, Vintage Pharmaceuticals and Watson Laboratories.

Metoclopramide is used to treat digestive tract problems, but, as the Supreme Court noted, evidence has accumulated to show that long-term use of the drug can cause tardive dyskinesia.  As a result, warning labels for the drug have been strengthened and clarified several times.  The two respondents in the case were prescribed Reglan in 2001 and 2002, but were issued with generic alternatives; after taking the drugs for several years, both developed tardive dyskinesia.  In separate legal actions, both sued the generic firms which manufactured the drugs they had taken, alleging that the condition had occurred as a result of taking the drug, and further alleging that generic manufacturers were liable under state tort law for failing to provide adequate warning labels.  In their defence, the generic firms argued that federal statutes and FDA regulations had pre-empted the state tort claims by requiring the same safety and efficacy labelling for generic metoclopramide as was mandated at the time for Reglan.  However, the lower courts had rejected this defence, leading to an appeals process which reached the Supreme Court.

Supreme Court finds in favour of generic firms

The Supreme Court found in favour of the generic firms, in a ruling which was not surprisingly welcomed by the generic drug industry.  However, the industry noted that its defence was that federal regulations had tied its hands, leaving it unable to alert consumers to issues which are not present in equivalent branded drug labelling.  At the time, Actavis’ CEO had commented that he believed a necessary next step would be for Congress to amend the law.

Senator Leahy noted that three years earlier the Supreme Court had held that a patient could sue a brand-name drug manufacturer for failing to warn because the brand-name manufacturer is permitted by law to update its warning.  The senator noted that in that case the plaintiff had been a resident of Vermont who had sustained life-threatening injuries resulting from the use of a drug manufactured by Wyeth.

Senator Leahy commented, “The Mensing decision creates a troubling inconsistency in the law with respect to prescription drugs.  If a consumer takes the brand-name version of a drug, she can sue the manufacturer for inadequate warnings.  If the pharmacy happens to give her the generic version, she will not be compensated for her injuries.  The result is a two-track system that penalises consumers of generic drugs – even though many consumers have no control over which drug they take, because state law and their health insurance plan require them to take generics if they are available.  I will introduce legislation to address this contradiction so that consumers are fully protected from harm and receive adequate warnings.”  Senator Leahy commented that he had been working to craft legislation that would permit generic manufacturers to improve the warning information for their products in the same way as brand manufacturers, thus providing adequate warnings to consumers.  This, of course, would also make generic manufacturers liable for deficiencies in their drug labelling, thus overturning the Supreme Court’s decision in the Mensing litigation.  At the time of writing, the legislation has yet to be introduced to the Senate.

Article source: Ian Platts, editor of World Generic Markets

Teva launches authorised generic modafinil, gains exclusivity and enters stormy waters

On 30th March 2012, Teva Pharmaceutical Industries announced that it had launched its authorised generic version of Provigil (modafinil).  Provigil is marketed by Cephalon, which recently became a wholly-owned subsidiary of Teva’s.  Teva commented that the product would continue to be manufactured under the brand product’s NDA at the same facility where it is currently manufactured.  The firm added that according to IMS sales data, the brand product had sales worth some US$1.1 billion in the US.

Separately, and in a somewhat odd twist, on 5th April 2012 Teva further announced that the FDA had decided that its wholly-owned subsidiary, Teva Pharmaceuticals USA, was the sole first-to-file for both Orange Book patents listed for Provigil.  Thus Teva’s ANDA alone would be entitled to the 180-days marketing exclusivity.  Teva noted that its other subsidiary, Cephalon, had launched a generic version of the drug, for which Cephalon holds the NDA, on 29th March.  Teva reported that the FDA had also decided that this launch triggered the exclusivity.  Teva added that it expected Par Pharmaceutical Companies to launch a second generic product on 6th April, pursuant to an agreement with the Federal Trade Commission in connection with its acquisition of Cephalon.

When the FTC approved Teva’s acquisition of Cephalon, it requested certain actions to be taken with regard to three products, one of which was Provigil.  With regard to Provigil, the FTC noted that at the time of the acquisition, no companies marketed a generic version of the drug.  However, Teva, Ranbaxy Pharmaceuticals, Mylan Pharmaceutical and Teva subsidiary Barr Laboratories had all taken steps to enter the market, and all were eligible to seek the 180-day marketing exclusivity for being the first to file an ANDA for the product.  However, the FTC noted that each company had signed an agreement with Cephalon not to market a generic version until April 2012.  The FTC contended that without this agreement, Teva and Cephalon would have been two of only a limited number of suppliers of modafinil during the 180-day period.  In order to replace the competition potentially lost through the acquisition, the FTC proposed a settlement order which included requiring Teva to enter into a supply agreement to provide Par with generic modafinil tablets in the US for one year.  This would allow Par to compete with a generic modafinil product during the 180-day exclusivity period.  In addition, Par could extend the agreement for a second year.  On 6th April, Par confirmed that it had begun shipping all strengths of modafinil tablets, and noted that its initial shipments would comprise generically-labelled presentations of the Provigil product.

However, a day earlier, on 5th April 2012, Mylan announced that its subsidiary, Mylan Pharmaceuticals, had filed a lawsuit in the US District Court for the District of Columbia against the FDA.  The lawsuit sought to overturn the FDA’s decision to award sole 180-day exclusivity for the generic version of Provigil.  Mylan’s complaint alleged that Teva did not maintain valid Paragraph IV certifications as a result of its acquisition of Cephalon.  The complaint stated that once Teva became the owner of Cephalon, it could no longer infringe the Provigil patents through a Paragraph IV certification, as it now owned the patents it was alleging in the certification to be either invalid and / or unenforceable, or else not infringed.  Consequently, Mylan argued, Teva was therefore not entitled to exclusivity based on patent certifications.  Mylan also alleged that the FDA should have found that Mylan was the sole first-filer on one of the Orange Book patents for Provigil, that Teva had abandoned its ANDA, and that the FDA should have approved Mylan’s ANDA for the product.  Mylan added that it was seeking an immediate order from the court entitling it to exclusivity and immediate approval for its ANDA.

Mylan’s complaint also alleged that the FDA’s decision, which blocked Mylan and other generic entrants from launching their generic Provigil products, was unlawful.  Mylan commented that it believed that the FTC did not contemplate the current outcome when it imposed its conditions on Teva’s acquisition of Cephalon.  Mylan noted that as a result of the FDA’s decision, only one party – Teva / Cephalon – controlled 100% of the supply of the product in the marketplace.  This, the firm added, was despite the fact that Cephalon had previously agreed to a Mylan launch of its generic version no later than 6th April 2012.

According to the FDA’s Orange Book, Provigil is protected by two patents, numbers 7,297,346 and RE37,516.  The ’346 patent expires on 29th November 2023, but has additional paediatric exclusivity until 29th Ma 2024; and the ’516 patent expires on 6th October 2014, but has additional paediatric exclusivity until 6th April 2015.  The FDA’s website currently shows no generic versions of the drug to have been approved.  However, tentative approvals have been granted to Mylan Pharma, Ranbaxy Laboratories, Teva Pharmaceuticals USA, Barr Laboratories, Carlsbad, Sandoz, Apotex, Caraco Pharmaceutical Laboratories and Orchid Healthcare.  Mylan’s version gained tentative approval on 4th April 2012.

Modafinil is a wakefulness-prompting agent for oral administration.  It is indicated to improve wakefulness in adults patients with excessive sleepiness associated with narcolepsy, obstructive sleep apnoea, and shift work disorder.  In obstructive sleep apnoea, modafinil is indicated as an adjunct to standard treatments for the underlying obstruction.

Article source: Ian Platts, editor of Espicom’s business publication, World Generic Markets

On 13th March 2012, AstraZeneca announced that it had filed a lawsuit against the FDA in the US District Court for the District of Columbia to overturn the agency’s 7th March 2012 decision to deny the firm’s citizen petitions regarding Seroquel (quetiapine fumarate) tablets and Seroquel XR extended-release tablets.  The petitions had requested that the FDA withhold granting final approval of any generic quetiapine products with labelling that omits certain hyperglycaemia warning language that the FDA required AstraZeneca to include in its labelling.

AstraZeneca commented that with the lawsuit it was seeking an injunction barring the FDA from granting final marketing approval of generic quetiapine products until 2nd December 2012, when regulatory exclusivity expires on clinical trial data, or alternatively, at least until a federal court has a meaningful opportunity to review imminent FDA action regarding the pending generic marketing applications.

According to the FDA’s Orange Book, Seroquel was protected by one patent, number 4,879,288.  This expired on 26th September 2011, but had an additional six months of paediatric exclusivity until 26th March 2012.  Seroquel XR was also protected by this patent, along with a second patent, number 5,948,437, which expires on 28th May 2017, but had paediatric exclusivity until 28th November 2017.  Although the FDA has yet to approve any generic versions of either product, with the first patent having now expired, it is likely that AstraZeneca will soon face competition, a consideration which no doubt played a part in the citizen petitions.  AstraZeneca noted that it has granted Handa Pharmaceuticals and Accord Healthcare licences to enter the US market with generic versions of Seroquel XR on 1st November 2016.

Ian Platts – Editor, World Generic Markets

World Generic Market Report 2012 – Author

Welcome back to the Pharmaceutical News. We’re kicking off this week with a run of articles for Espicom’s excellent business publication World Generic Markets, please read on…

Difficult times for AstraZeneca

March and April 2012 proved to be a difficult few weeks for AstraZeneca, which saw its products come under pressure from generic competitors in North America and Europe.  In Canada, the firm’s statin product, Crestor (rosuvastatin), faced generic competition, with announcements from Ranbaxy Laboratories and Apotex of generic launches.  Apotex noted that the approvals came some eight years ahead of the relevant patents’ expiration.  South of the border, in the United States, AstraZeneca has yet to face generic competition for Crestor; the product here is protected by a number of patents, with the last patent expiration dates reaching 2021, with paediatric extensions into 2022.  However, AstraZeneca cannot afford to be complacent; the FDA lists a number of generic versions of the drug which have been granted tentative approvals, from eight different companies.  Crestor also faces a slightly different threat in the US, through Watson Laboratories, which has filed an NDA for a rosuvastatin zinc product, and gained tentative approval for the application in August 2011.  This is different from Crestor, which contains rosuvastatin calcium, but uses Crestor as a reference drug.  AstraZeneca is currently in litigation with Watson over the product; AstraZeneca is claiming patent infringement, and has filed a lawsuit under the provisions of the Hatch-Waxman Act, providing some breathing space, as the FDA will be prevented from issuing a final approval until April 2013, unless the court finds in Watson’s favour.  In March 2012, Egis reported that it has been named as a defendant in the litigation between AstraZeneca and Watson.  Egis has been added to the litigation because it was responsible for the development and manufacturing of Watson’s rosuvastatin zinc product.  Egis noted that AstraZeneca is not seeking monetary damages against it.  Nonetheless, Egis has vowed to defend itself in the litigation.

AstraZeneca court injunction dismissed

Perhaps AstraZeneca’s biggest headache in March and April has been over Seroquel, the firm’s quetiapine product, which has faced competition in both the United States and Europe.  In the US, Seroquel was protected by one Orange Book-listed patent, but this expired in September 2011, with its paediatric extension expiring on 26th March 2012.  AstraZeneca had been fighting a rearguard action, and had filed a lawsuit against the FDA, which had aimed to overturn an earlier agency denial of a Citizen Petition regarding the drug.  However, on 23rd March 2012, AstraZeneca reported that the court denied its request for a preliminary injunction and dismissed the lawsuit, albeit without prejudice.  With the patent paediatric exclusivity expiring on 26th March, a day later the FDA approved ten generic versions of the drug.

However, AstraZeneca was able to take comfort from a second court ruling in the United States: on 29th March 2012, the New Jersey court announced that the formulation patent protecting Seroquel XR, AstraZeneca’s extended-release product, was valid.  The court also ruled that three companies, Anchen Pharmaceuticals, Osmotica Pharmaceutical and Mylan had infringed the patent with their proposed generic versions.  Currently there are no generic versions of Seroquel XR approved in the US, and, unlike the non extended-release version, has patent protection until the end of 2017.

UK High Court finds Seroquel XR patent invalid

On the other side of the Atlantic, however, the news has not been so good.  On 22nd March 2012, AstraZeneca reported that the United Kingdom’s High Court had found the formulation patent for Seroquel XR to be invalid.  AstraZeneca did its best to downplay the news, pointing out that this was the first court decision to go against the patent, and added that the courts in the Netherlands had affirmed the patent’s validity.  Nonetheless, the UK court decision was followed by news of launches of generic quetiapine film-coated tablets and quetiapine XL tablets in the UK, along with Denmark, Germany, Italy, Ireland, the Netherlands and Romania.  Companies launching the generics included Teva UK, Consilient Health and Actavis, which added it had also launched in Sweden.

Finally, on 21st March 2012, Actavis also announced that it had launched its generic zolmitriptan and zolmitriptan orodispersible tablets in various countries, including the UK, France, Italy, Denmark, Norway, Sweden and Finland, following patent expiration.  The product is a generic equivalent of AstraZeneca’s Zomig.  Actavis was already marketing its version in Malta, Romania and Ukraine.  A few days later, Teva UK announced that it had also launched its zolmitriptan orodispersible and film-coated tablets in the UK.

In many ways, the new European generic zolmitriptan competition is the least concerning for AstraZeneca.  Actavis indicated that according to IMS figures, European sales of zolmitriptan were worth some US$152 million.  However, worldwide sales for rosuvastatin and quetiapine are estimated to be worth towards US$9 billion between them.  Generic competition for these two products in the advanced markets of North America and Europe are clearly going to threaten a significant chunk of AstraZeneca’s global turnover, which the company put at some US$33.6 billion in 2011.

Ian Platts – Editor, World Generic Markets

Amgen and AstraZeneca have entered into an agreement to jointly develop and commercialise the following five monoclonal antibodies from Amgen’s clinical inflammation portfolio:

• brodalumab (AMG 827), which binds to and blocks signalling via the interleukin-17 receptor, is being investigated for psoriasis (completed Phase II and planned Phase III), psoriatic arthritis (Phase II) and asthma (Phase II);

• AMG 139 is in Phase Ib for Crohn’s disease;

• AMG 181 is in Phase Ia and Ib trials for ulcerative colitis and Crohn’s disease;

• AMG 557, which binds to B7-related protein 1, is in Phase Ib for autoimmune diseases such as systemic lupus erythematosus; and

• AMG 157, which blocks interaction of thymic stromal lymphopoietin with its receptor, is in Phase Ib for asthma.

The collaboration will provide Amgen with additional resources to optimally progress its portfolio, and Amgen will benefit from the strong respiratory, inflammation and asthma development expertise of MedImmune, AstraZeneca’s biologics arm. The collaboration will also capitalise on AstraZeneca’s global commercial reach in respiratory and gastrointestinal diseases. The agreement does not include certain territories previously partnered by Amgen for brodalumab with Kyowa Hakko Kirin and AMG 557 with Takeda.

Under the terms of the agreement, AstraZeneca will make a one-time US$50 million up-front payment, and the companies will share both costs and profits. Based on current plans, approximately 65 per cent of costs for the 2012 to 2014 period will be funded by AstraZeneca. Thereafter, the companies will split costs equally. Amgen will book sales globally and retain a low single-digit royalty for brodalumab and a mid-single-digit royalty for the rest of the portfolio, after which the companies will share profits equally.

AstraZeneca will lead the development and commercial strategy of AMG 139, AMG 157 and AMG 181, while Amgen will lead the development and commercial strategy of brodalumab and AMG 557. Each development and commercialisation lead will be under the oversight of joint governing bodies. For brodalumab, commercial promotion will be split. Amgen will promote in dermatology indications in the US and Canada, and in rheumatology indications in the US, Canada and Europe. AstraZeneca will promote in respiratory and, initially, dermatology indications of brodalumab across all territories outside of the US, Canada and those markets where Amgen has existing partnerships. Allocation of promotional rights for other territories, indications and molecules will be agreed later between the companies.

Natco Pharma gains compulsory licence for sorafenib tosylate

On 12th March 2012, Natco Pharma reported that it had been granted a compulsory licence, under the provisions of Section 84 of the Indian Patents Act, 1970, for sorafenib tosylate, the generic form of Bayer’s Nexavar.  The firm noted that Nexavar is a first-line treatment for liver and kidney cancer.  Natco commented that the compulsory licence was the first of its kind to be granted by the Indian government.  It enables Natco to sell its version of the drug at a price not exceeding Rs8,880 (US$173.38) for a pack of 120 tablets, representing one month’s therapy.  This compares to the brand price of Rs284,428 (US$5,553.34) charged by Bayer.  The licence will be valid until the expiry of the relevant patent in 2021.  Natco noted that the order is subject to certain conditions, such as maintaining account of sales and payment of a royalty at 6% of net sales on a quarterly basis.  The order also obligates Natco to supply the drug free of cost to at least 600 patients per year.

Decision welcomed by pressure groups

The move has generated a number of comments.  James Love, of the organisation Knowledge Ecology International (KEI), a not for profit non-governmental organisation concerned with the management of knowledge resources, commented that Bayer’s price for Nexavar in India is Rs3,411,898 (US$66,615.86) per year.  Mr Love commented that this was more than 41 times the projected average per capita income for India in 2012.  According to Mr Love, Bayer had tried to justify the price by making claims of high research and development costs, but refused to provide any details regarding its actual outlays on the research for sorafenib; Mr Love added that the research for the drug was partly subsidised by the United States Orphan Drug tax credit, and was jointly developed with Onyx Pharmaceuticals.  Mr Love further added that Onyx had informed the US Security and Exchanges Commission that the cost of R&D, pre-Orphan Drug tax credit, was US$275 million through the 2005 FDA approval of sorafenib, including outlays on other compounds, indications that were not approved for marketing, and for expanded access trials in the US that had limited value as scientific experiments.  Mr Love argued that Bayer has made billions of dollars from sorafenib, and had made little effort to sell it in India, where it is priced beyond the means of most of the population.

KEI, which had filed an affidavit in the case, reported that Natco had sought the compulsory licence under three grounds of Section 84 of the Patent Act, all of which were upheld in the government’s decision:

• That the reasonable requirements of the public with respect to the patented invention had not been satisfied; or

• That the patented invention is not available to the public at a reasonably affordable price; or

• That the patented invention is not worked in the territory of India.

KEI noted that Bayer’s main defence of the pricing was its programme of discounts to lower income patients and the fact that Cipla was selling an infringing product at a lower price.  KEI added that Bayer is in the process of suing Cipla, and requesting damages and injunctions.

In a statement for KEI, Mr Love commented that the Controller General of Patents and Trade Marks in India had ‘rightly’ rejected Bayer’s defences in what Mr Love described as an early test of the India requirement that patent monopolies will be limited when products are not ‘reasonably affordable’.  Mr Love argued that had the compulsory licence been denied, the India statute on ‘reasonably affordable’ pricing would have been an empty protection for the public.

Mr Love noted that the decision granting the licence to Natco was limited.  Only Natco is allowed to manufacture under the compulsory licence; Cipla would have to seek its own licence should it wish to pursue this avenue.  Natco will not be able to import the drug to satisfy the Indian market; Mr Love commented that this restriction was not important in India, but would be very difficult if imposed outside of India, where the capacity to manufacture with efficient economies of scale and scope are limited.  Mr Love added that KEI was pleased that the Controller had cited the evidence of inadequate access as a test of the affordability of the product.

KEI commented that Bayer was expected to appeal the decision.  The organisation added that India had taken a first step toward protecting its public from high prices on patented drugs, and hoped that this would lead to more standardised policies for granting compulsory licences when products are too expensive to be affordable to many.

Médecins sans Frontières also welcomed the decision.  Dr Tido von Schoen-Angerer, director of the organisation’s Access Campaign, commented, “We have been following this case closely because newer drugs to treat HIV are patented in India, and as a result are priced out of reach.  But this decision marks a precedent that offers hope: it shows that new drugs under patent can also be produced by generic makers at a fraction of the price, while royalties are paid to the patent holder.  This compensates patent holders while at the same time ensuring that competition can bring down prices.”  Michelle Childs, director of policy / advocacy at the Access Campaign added that the decision served as a warning.  “When drug companies are price gouging and limiting availability, there is a consequence: the Patent Office can and will end monopoly powers to ensure access to important medicines.”  Médecins sans Frontières commented that the move mirrored similar decisions made in other countries, including the US.  The organisation explained that in February 2011, the US Patent Office decided not to prevent a ‘generic’ medical device used for skin grafts from being sold, but instead insisted that its manufacturer pay royalties to the patent holder.

PhRMA is critical

In the United States, PhRMA, the Pharmaceutical Research and Manufacturers of America organisation, was critical of the decision.  The organisation commented that the research-based pharmaceutical industry believes that all people around the world should have access to quality healthcare and lifesaving medicines, and added that in partnership with other stakeholders, the industry is committed to playing a full part in addressing the healthcare challenges of the developing world by taking an innovative, responsible and sustainable approach.  PhRMA President and CEO, John Castellani, commented, “while India has not routinely issued compulsory licenses, PhRMA believes it is not an appropriate tool even if granting compulsory licenses may be a legal option.  Assessments of particular compulsory licensing policies and decisions need to be made on a case-by-case basis, taking into account a number of factors.  Legitimate health emergencies that require making exceptions to intellectual property rights can and should be accommodated under the international framework, but only after exhausting all other efforts and under extraordinary circumstances.”

Mr Castellani added that PhRMA would not address the specifics of the case.  “However, one aspect that is particularly troublesome is the contention that ‘working’ a patent requires a company to manufacture within India.  It is our firm belief that this is fully at odds with India’s TRIPS commitment (as well as broader WTO obligations), and distorts what was intended as a public health exception into an industrial policy.”  Mr Castellani added that whilst the research-based pharmaceutical industry supported the objective of improving access to medicines, compulsory licenses “… cannot solve India’s larger problems regarding access to medicines and healthcare.  If countries begin to routinely use compulsory licences, we could see a ‘race to the bottom’ in which governments in the developing world walk away from their responsibility to support research and innovation in public health.  In the absence of the investment made by our members, and the resulting research and development, there would be no generic medicines for the world’s patients.  The responsibility to promote development of new drugs lies with all countries, not solely those in the developed world.”

Ian Platts – Editor, World Generic Markets

Author – World Generic Market Report 2012

Spectrum Pharmaceuticals has seen mixed fortunes recently

….On the positive side, the company is seeking to strengthen its position in the haematology area and has agreed to pay up to US$206 million, plus additional consideration if certain milestones are met, for Allos Therapeutics. On the downside, its lead compound, apaziquone, has failed to meet the primary endpoint of a statistically significant difference in the rate of tumour recurrence at two years in both Phase III trials investigating it for the treatment of non-muscle-invasive bladder tumours. Spectrum had expected to file an NDA for apaziquone in 2012.

However, it might not be all bad news for this drug, as an analysis of the pooled data from both studies showed a statistically significant treatment effect in favour of apaziquone in the primary endpoint and a key secondary endpoint. Thus, Spectrum is currently weighing up its options on whether to proceed with this drug in the future.

Spectrum share price takes a hit

On the back of this mixed news, Spectrum’s share price tumbled by 9.4 per cent from US$12.21 to US$11.06, whereas investors in Allos were more impressed with the takeover news, leading to a rise of 27.3 per cent in its shares from US$1.43 to US$1.82, both at close of day on 4th and 5th April, respectively.

Spectrum currently sells two oncology drugs, Zevalin (ibritumomab tiuxetan), which is approved to treat a form of non-Hodgkin’s lymphoma, and Fusilev (levoleucovorin), which treats the side effects of methotrexate. For 2011, Zevalin sales declined by 4.5 per cent to US$27.6 million, whereas Fusilev posted sales of US$153 million, up from US$32 million in 2010.

The acquisition of Allos, which is expected to be accretive to Spectrum on a cash basis in the fourth quarter of 2012, will bring a new revenue stream in the form of Folotyn (pralatrexate), a novel dihydrofolate reductase inhibitor that was approved by the FDA in September 2009 for patients with relapsed or refractory peripheral T-cell lymphoma. The product generated US net sales of US$50 million in 2011. Allos and Mundipharma have a strategic collaboration to co-develop Folotyn; Allos retains full commercialisation rights in the US and Canada, while Mundipharma has exclusive rights in all other countries. Mundipharma has submitted various applications seeking regulatory approval of Folotyn, including in Australia, South Korea and Switzerland. Unfortunately, in Europe, at its January 2012 meeting, the EMA’s CHMP issued an opinion recommending against conditional approval of Folotyn due to concerns about the study submitted in support of the application.

Rajesh C Shrotriya, Chairman, CEO and President of Spectrum stated: “For Spectrum, this acquisition adds another diversified source of revenue, accelerates the development of our haematology franchise and affirms our commitment to becoming a leader in the treatment of lymphoma. Zevalin and Folotyn are targeted to the same haematologists/oncologists for the treatment of different forms of lymphoma.”

Article source: Cancer Drug News edited by Ros Smallman.