Regulatory and clinical developments over the Christmas period

Outside the deal-making sphere news was pretty thin on the ground over the holiday period. Notable events included final EU approval for Roche’s Avastin in ovarian cancer as well as confirmation that the drug is unlikely to be filed in the US in this use; broad European approval for United Therapeutics’ intravenous Remodulin and a US filing for the oral version; and a timeline for the fresh regulatory review of Vivus’s Qnexa in the wake of data confirming the drug’s worrying side effects.

Teva meanwhile grabbed headlines on the first day of the year by announcing the surprise exit of chief executive Shlomo Yanai. In what is seen as a strong hire for the Israeli generics firm – and a big loss to Bristol-Myers Squibb - he will be replaced by the US pharma giant’s executive Jeremy Levin in May.

January 1

Teva’s chief executive Shlomo Yanai has led the Israeli generics giant for five years, overseeing a string of acquisitions that more than doubled the groups revenues – analysts expect 2011 sales to hit $18.26bn – and took the company further into branded and OTC products.

The company’s shares lost a fifth of their value last year on concern about the impending loss of market exclusivity for its biggest selling drug, MS therapy Copaxone, and fears ambitious long term growth targets will be missed. The company’s Israeli-listed stock has advanced 4.5% to NIS16,050 on news of the change at the top. Mr Levin was responsible for Bristol-Myers’ successful “string of pearls” acquisition strategy and is widely respected as a canny deal maker; hiring a big pharma name suggests Teva’s attempts to grow its non-generics business are likely to continue.

December 29

Amgen said the FDA’s Oncologic Drugs Advisory Committee (ODAC) will review its application to approve Xgeva in preventing the spread of prostate cancer to the bone on February 8 (Amgen data confirms Xgeva potential, December 14, 2010). A PDUFA date of April 26 has been set.

Xgeva, a RANK ligand inhibitor, is currently approved to prevent skeletal-related events in patients with bone metastases from solid tumours; the second indication could be a major growth driver for the product.

The ODAC panel will also review on February 9 the sNDA for Dacogen, submitted by Eisai, to treat elderly patients with acute myelogenous leukaemia (AML). Dacogen is approved for the treatment of myelodysplastic syndromes (MDS) in about 30 countries outside of the US, where it is being developed and marketed by Johnson & Johnson. The drug as a treatment for MDS loses orphan drug protection in 2013 (EP Vantage Interview - Astex looks past Dacogen horizon, September 29, 2011).

J&J filed for US approval to expand the use of oral anticoagulant Xarelto, to reduce the risk of secondary cardiovascular events in patients with acute coronary syndrome. Strong data from the pivotal Phase III trial conducted in this setting was presented at the American Heart Association meeting in November (AHA 2011 - Xarelto proves its worth with strong ACS data, November 14, 2011).

Gentium meanwhile said it anticipates submitting a response to the Day 120 list of questions from the EMA in the first quarter of 2012, with regard to its filing for defibrotide. The product would be the first approved treatment for the prevention of hepatic veno-occlusive disease (VOD) in adults and children undergoing haematopoietic stem-cell transplantation therapy.

December 28

Promising pre-clinical data was published in the journal Experimental Neurology on Alnylam Pharmaceuticals' ALN-HTT programme, an RNAi therapeutic drug-device combination being developed for Huntington's disease in partnership with Medtronic.

The paper described how a small interfering RNA (siRNA) targeting the huntingtin gene, administered by intrastriatal infusion with convection-enhanced delivery (CED), results in widespread distribution of the siRNA and significant silencing of the huntingtin mRNA throughout the striatum. The therapeutic was well tolerated and the companies plan to undertake further work.

December 27

Perrigo Company received final FDA approval for its generic version of hayfever treatment Clarinex. Under the terms of a settlement struck with Schering-Plough in 2008 Perrigo can launch on July 1 2012; the product is predicted to be the company’s second biggest sales growth driver.

French regulators approved United Therapeutics intravenous Remodulin for the treatment of pulmonary arterial hypertension; following reviews by 22 European member nations, the product will now be available in most European countries.

The company also said it filed for US approval for an oral version of the drug, and is expecting a standard 10 month review period. With underwhelming phase III results for oral treprostinil it remains to be seen whether FDA approval will be granted (United punished as oral Remodulin flops again, August 24, 2011).

December 26

Eisai resubmitted its filing for AMPA receptor antagonist perampanel (E2007) to the FDA. The product is indicated for the treatment or partial-onset seizures associated with epilepsy.

The FDA issued a Refusal to File letter in July 2011 in which reformatting and reanalyses of some datasets were requested. The MAA for perampanel is currently under regulatory review in Europe and under phase II studies in Japan as well as in global phase III studies for generalised epilepsy. If approved, perampanel will be the first product in this class of anti-epileptic drugs.

December 23

On February 22, the Endocrinologic and Metabolic Drugs Advisory Committee of the FDA will review Vivus’s Qnexa for the treatment of obesity; a PDUFA date of April 17 has been set.

Data from the recently completed Fortress safety review will be a focus; on December 21 the company released data confirming the link between topiramate, an ingredient of Qnexa, and oral clefts in infants of women exposed during pregnancy.

Thrombogenics filed ocriplasmin with the FDA for approval as a treatment of symptomatic vitreomacular adhesion including macular hole. In October 2011, the EMA accepted the drug for review for the same indication. If approved ocriplasmin will be the first pharmacological treatment for VMA, potentially removing the need to operate – the only treatment option currently available (EP Vantage Interview - ThromboGenics eyeing approval success, December 23, 2011).

Following the withdrawal of Avastin for breast cancer back in June Roche received final EU approval of the drug as a front-line treatment for women with advanced ovarian cancer. However, detailed results published in the New England Journal of Medicine a couple of days later prompted comments from the company confirming approval in the US is unlikely to be sought, in the near future at least.

The two trials - GOG-0218 and ICON 7 – demonstrated a modest benefit over standard chemotherapy in terms of progression-free survival, but little if any evidence of prolongation of survival has emerged so far. The FDA has previously said that it wants to see an improvement in overall survival from these studies (Avastin in ovarian gets EU backing but US will be harder won, September 26, 2011). Roche is awaiting final overall survival data to make a decision.

The FDA set a PDUFA date of August 27 for Gilead’s Quad pill. The combination product is the company’s most important sales growth driver with revenues of $842m forecast for 2016, according to EvaluatePharma.

Finally, SkyePharma announced another delay to the decision in Europe over approval of asthma drug Flutiform. After member states could not reach a unanimous decision the process will go to arbitration, which could add another 10 months to any decision, analysts believe. Shares in the heavily indebted company dropped 16% on the news, to 33p (Event - SkyePharma holding breath for crucial Flutiform approval, August 18, 2011).

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