DID - April 8, 2008 Issue

Vol. 7 No. 69

Alcon Set to Become Novartis Subsidiary

Nestle is selling part of its stake in Alcon in a $39 billion deal that could make the eye care company a Novartis subsidiary.

Under the terms of the agreement, Novartis will acquire a 25 percent stake in Alcon from Nestle for $11 billion. The company also has rights to purchase Nestle’s remaining 52 percent stake in Alcon for $28 billion between January 2010 and July 2011. During that period, Nestle has the right to require Novartis to purchase the remaining stake for a 20.5 percent premium over the market capitalization of Nestle’s Alcon holdings, not to exceed $28 billion.

Alcon had sales of $5.6 billion in 2007. The firm was purchased by Nestle in 1978, but a portion of the company was divested in 2002. Novartis says it plans to borrow $5.5 billion to finance its initial purchase. The transaction is subject to regulatory clearance.

The combination would merge two of the world’s largest eye care businesses. In 2006, Novartis had 13 percent of the $25 billion eye care market, while Alcon claimed 24 percent, Novartis said. Novartis cited Alcon’s pipeline, strong sales force and excellent relationships with key opinion leaders as benefits.

Alcon has a new drug application pending at the FDA for antihistamine nasal spray Patanase (olopatadine HCl) (DID, Oct. 15, 2007). It also has an application pending for its TobraDex (tobramycin/dexamethasone) follow-on TobraDex ST. TobraDex is an ophthalmic suspension that has been the most frequently prescribed anti-infective/anti-inflammatory combination on the market for 20 years, Alcon said.

The company is expected to file an NDA this year for a new formulation of Vigamox (moxifloxacin HCI), which is used to treat eye infections.

In addition, Alcon markets the AcrySof ReSTOR lens, an intraocular lens implantable after cataract surgery. It also sells the Infiniti and Laureate systems for cataract surgery, and the firm’s Accurus system is used for procedures on the back of the eye. Alcon sells the Allegretto Wave laser eye surgery system for correcting vision as well. — Christopher Hollis


Study Shows Bright Future for Enbrel

A survey of rheumatologists indicates the rheumatoid arthritis drug Enbrel will not be replaced any time soon as the standard of care by other drugs under development.

According to the report “Rheumatoid Arthritis: Competitive, Crowded Market Sets the Bar High for Novel Agents,” doctors consider Amgen’s, Wyeth’s and Takeda’s Enbrel (etanercept) the most advantageous drug for rheumatoid arthritis.

The main clinical outcomes and drug delivery features that influence rheumatologists’ choice of a prescription to treat rheumatoid arthritis are efficacy (reducing signs and symptoms of rheumatoid arthritis and inhibiting or slowing the progression of structural damage at one year); safety and tolerability (serious infections); and delivery (onset of action).

The research done to prepare the report includes both current and developing drugs through 2016. Among included drugs are the following:

  • Golimumab (CNTO 148);
  • Ocrelizumab (anti-CD20);
  • Cimzia (certolizumab pegol);
  • Rheumatrex (methotrexate);
  • Humira (adalimumab);
  • Orencia (abatacept);
  • MabThera (rituximab); and
  • Actemra (tocilizumab).

The most promising agents expected to launch by 2016 are certolizumab pegol or golimumab, which “could fulfill the requirements of the minimal acceptable profile,” the report said. However, the authors said more data is needed on those drugs’ ability to induce remission in a larger percentage of patients than etanercept when used in combination with methotrexate, to slow structural damage progression after two years of treatment and to lower the rate of serious infections. — Yuliya Melnyk


EC Approves New Pediatric Formulation of Kaletra

Abbott Laboratories received European Commission (EC) approval for its new pediatric tablet formulation of Kaletra, a combination antiretroviral drug indicated for the treatment of HIV-1 in adults and children over the age of 2.

The new tablet offers advantages over Kaletra’s (lopinavir/ritonavir) other pediatric formulations, the soft gel capsule and oral solution. For example, the soft gel capsule is only supposed to be taken with food, unlike the new tablet formulation. Also, the tablet does not need to be refrigerated as does oral solution.

The new pediatric formulation contains lower doses of the active ingredients than the adult version.
Starting in May, Abbott plans to launch the new product in the UK, Germany and Sweden. The company said approximately 4,000 children are infected with HIV in Europe.

EC approval of the new tablet is significant for developing nations as they use the Certificates of Pharmaceutical Products, which are based on European marketing clearance, to approve drugs, Abbott said.

The drug will be priced at half the cost of the adult formulation, which costs $500 annually in Africa, Abbott said. There are an estimated 2.5 million children under the age of 15 living with HIV in undeveloped nations, 90 percent of whom live in sub-Saharan Africa.

Abbot told DID that it is still in negotiations with the Thai government over a compulsory license the country instituted for Kaletra, which caused the firm to temporarily stop selling the drug in Thailand (DID, May 9, 2007).

Despite the issues surrounding the compulsory license in Thailand, the firm recently shipped the product to the nation, Abbott told DID. The company has a drug approval application for the new tablet formulation pending in Thailand. — Christopher Hollis


EPO Grants Protection for Crohn’s Candidate

The European Patent Office has given Australian drugmaker Giaconda a patent for Myoconda, a treatment for Crohn’s disease patients infected with Mycobacterium avium paratuberculosis.

Myoconda is a combination of rifabutin, clarithromycin and clofazimine, antibiotics used to treat mycobacterial and other infections.
The decision gives the company patent protection for the product in the European Union until April 2018. Patents have been granted in the U.S., Australia, New Zealand, South Africa, Israel and the Philippines.

In 2004, Pharmacia, the original developer of the drug, completed a Phase IIIa trial in which Crohn’s patients taking Myoconda demonstrated statistically significant improvement in achieving remission at 16 weeks compared with conventional therapy. However, the drug did not show statistically significant results in maintaining remission after completion of therapy.

After Pfizer and Pharmacia merged, Myoconda rights reverted to the Australian-based Center for Digestive Diseases, which sold the intellectual property for the drug to Giaconda. The company decided to revise the drug’s development program by increasing the dose of clofazimine, which Pharmacia had lowered in its trial.

Last September, Giaconda reported it had entered a deal with the Prague Clinical Services to conduct a Phase III trial to gain Myoconda approval from the UK’s Medicines and Healthcare products Regulatory Agency. The company said it might be required to perform a separate Phase III study, which it intends to conduct in the U.S., to gain FDA approval. — Elizabeth Jones


UK Commission Letter on Blood Substitute Cites Safety, Efficacy Concerns

 Biopure’s effort to get UK approval for its blood-substitute candidate Hemopure hit a snag as regulators said major issues remain involving safety, quality, clinical efficacy, reliability of data monitoring and auditing of clinical trials.

The Commission on Human Medicines noted the lack of data in trauma patients as a concern for the potential off-label use of Hemopure [hemoglobin glutamer - 250 (bovine)]. However, the agency invited Biopure to discuss these issues with a Medicines and Healthcare products Regulatory Agency (MHRA) team of medical, statistical and pharmaceutical reviewers.

Hemopure’s application was accepted for review in September 2006 and the MHRA issued its preliminary opinion letter in December 2006. The company had requested an indication for treatment of acutely anemic adult orthopedic surgery patients younger than 80. In its response to the preliminary opinion, submitted last November, Biopure changed the product’s indication to the treatment of acute anemia following orthopedic surgery blood loss when blood is not readily available or is not an option.

While the commission’s most recent letter said Biopure’s November response reassured the commission on several questions, it said major pharmacological and clinical issues were not yet or only partially resolved. However, the company noted the commission has not advised it to withdraw its application.

Biopure CEO Zafiris Zafirelis said the company will meet with the UK regulatory review team as soon as possible for clarification of their requirements. The firm will announce the date of its meeting with MHRA when it is set, as well as the outcome of the meeting and an anticipated timeline.

Biopure said one reason the commission has unresolved questions may be that the firm has not completed a clinical trial for anemia in patients for whom blood was not available or an option. Biopure is supporting the U.S. Navy’s government-funded efforts to develop a potential out-of-hospital trauma indication, the company said.

In December 2006, the FDA’s Blood Products Advisory Committee recommended the agency continue a clinical hold on the Navy’s trial of Hemopure (DID, Dec. 18, 2006). But Biopure said last January that the U.S. Navy agreed to buy Hemopure and seven different modifications of the treatment for preclinical testing. Calls to the company about the trial’s current status were not answered by press time.

Additional Trials

In a February SEC filing, the company said its second trial of Hemopure in patients undergoing percutaneous coronary intervention ended in late 2007. A key objective of the study was to observe whether intracoronary delivery of the treatment lessens ischemia.

Enrollment was stopped after the first five patients, although the protocol allowed for 10, because the investigator concluded the results showed a trend that proved the principle being tested, Biopure said.

A second safety trial, in patients undergoing limb amputation, also ended in late 2007, primarily because of slow enrollment due to a protocol design that did not account for different clinical practices across institutions and countries.

Biopure is scheduled to present at an upcoming public workshop given by the FDA, “Hemoglobin Based Oxygen Carriers: Current Status and Future Directions,” which will take place April 29–30.

Hemopure is approved for sale in South Africa for acutely anemic surgical patients. Sales of the product were $58,000 for the first quarter of 2008, according to the firm’s 8k filing with the SEC. — April Astor


Pharmacogenomics Terminology Guidance Covers Four Privacy Levels

The FDA took the final step to harmonize pharmacogenomic definitions and sample coding guidance with that of Japan and the European Union by issuing its own guidance for comment.

The guideline — E15 Definitions for Genomic Biomarkers, Pharmacogenomics, Pharmacogenetics, Genomic Data and Sample Coding Categories — provides definitions and additional information related to aspects covered by the definitions and notes that certain principles discussed in the document may be applicable to related disciplines such as proteomics and metabalomics.

Key definitions define genomic biomarker as a measurable DNA or RNA characteristic that is an indicator of normal biologic or pathogenic processes or a response to therapeutic or other interventions. They define pharmacogenomics as the study of variations of DNA and RNA characteristics as related to drug response. The also define and pharmacogenetics as the study of variations in DNA sequence as related to drug response.

The guideline also offers harmonized definitions for the four general coding categories of biological samples used to generate data in pharmacogenomic and pharmacogenetic studies:

  • Identified, as by a Social Security number or national insurance number;
  • Coded, without any personal identifiers;
  • Anonymized, where samples and data initially are single- or double-coded and the link between personal identifiers and unique codes is later deleted; and
  • Anonymous, or lacking both personal identifiers and coding.

A copy of the guidance is available at www.fda.gov/OHRMS/DOCKETS/98fr/FDA-2008-D-0199-gdl.pdf. — Yuliya Melnyk

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Reporters: Martin Gidron, April Astor, Christopher Hollis, Elizabeth Jones, Yuliya Melnyk

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