Drug Industry Daily - Aug. 25, 2010 Issue

Vol. 9 No. 165

Pfizer’s Sutent Fails in Phase III Lung Cancer Trial

Pfizer’s Sutent missed its primary endpoint of overall survival in a Phase III clinical trial of advanced non-small cell lung cancer (NSCLC) patients, though the drug showed improvement in progression-free survival.

Pfizer will analyze the data to try to identify patient subgroups for a future trial in either previously untreated or recurrent disease, the company said Monday. The trial examined patients with previously treated advanced NSCLC in combination with Genentech/OSI Pharmaceuticals’ Tarceva (erlotinib HCl).

Sutent is already approved for two cancer types: gastrointestinal stromal tumor after disease progression or intolerance to Novartis’ Gleevec (imatinib mesylate) and advanced renal cell carcinoma. Pfizer said it is committed to developing Sutent (sunitinib malate) for additional tumor types.

The company released only top-line data, but said it will present the full data set in October at the European Society for Medical Oncology Congress.

Other NSCLC Candidates Face Setbacks

Pfizer is not alone with its disappointment, as other companies have also faced setbacks recently in NSCLC drug development.

Allos Therapeutics’ Folotyn (pralatrexate) has demonstrated clinical activity comparing it with Tarceva in a Phase IIb, second-line treatment study of advanced NSCLC patients (DID, July 29). The study was not designed to show a statistically significant difference between the two treatments.

Merck KGaA and its U.S. subsidiary EMD Serono are resuming two Phase III studies of Stimuvax (BLP25 liposome vaccine) in patients with NSCLC after previously halting the trials due to a serious adverse event in a multiple myeloma trial (DID, June 18).

Abraxis BioScience plans to expand Abraxane (paclitaxel protein-bound particles) in other indications, including NSCLC, with an estimated sNDA filing in the first half of 2011 (DID, July 1).

Pfizer also plans a first half of 2011 NDA filing for crizotinib for NSCLC, as it recently began Phase III trials to see if the drug improves survival versus standard chemotherapy (DID, June 8). Earlier this year, Pfizer stopped a Phase III trial of figitumumab as a first-line treatment for advanced non-adenocarcinoma NSCLC but said it will continue studying the drug (DID, Jan. 4).

Bayer HealthCare Pharmaceuticals and Onyx Pharmaceuticals’ liver and kidney cancer treatment Nexavar (sorafenib tosylate) in June also failed to meet the primary endpoint of improving overall survival in a trial conducted to expand the drug’s indication to include a first-line treatment for advanced non-squamous NSCLC.

Additionally, Novartis stopped a Phase III trial of ASA404 (vadimezan) this year after an interim analysis found it was unlikely to improve patient survival as a first-line treatment. However, a trial observing ASA404 in second-line NSCLC is ongoing. — April Hollis


Roche Signs Potential $1.1 Billion Deal With Aileron for New Class of Drugs

Roche has agreed to provide up to $1.1 billion to Aileron Therapeutics to develop a new class of drugs known as stapled peptides that have the potential for use across multiple therapeutic areas.

Aileron gets at least $25 million in technology access fees and R&D support, according to the deal announced Tuesday. The $1.1 billion is based on payments that will be made following discovery, development, regulatory and commercialization milestones.

Roche will work with Aileron to develop drug candidates against up to five undisclosed targets in Roche’s key areas: oncology, virology, inflammation, metabolism and central nervous system disorders.

The deal with Roche follows a 2009 agreement in which Roche, along with Novartis, GlaxoSmithKline and Eli Lilly, together pledged $40 million in financing to Aileron, which is privately held.

Aileron CFO Steven Kafka said it is telling that Roche calls his company’s technology transformative. Stapled peptides are promising therapies because they can penetrate cells and bind specifically to proteins. “That gives the possibility of now creating drugs for targets that we couldn’t reach with existing approaches,” he said.

Kafka said it was important the collaboration be centered on very specific targets because the stapled peptide platform has potential across a variety of therapies and dozens, if not hundreds, of targets.

Aileron will take on substantial responsibility to develop drug candidates against the selected targets. However, there will be a wall between Roche-only targets and collaborations with other drug companies, Kafka explained. “Once we are working together with Roche on that target, we are working with Roche on that target: a specific protein-on-protein interaction.”

Kafka said it is hard to predict when clinical trials of any potential drug candidates would launch.

“The promise here is reaching targets that are not currently drugable by existing approaches,” he explained. “By stabilizing peptides, we can confer properties that in a way combine the best features of antibodies and small molecules, specifically getting them inside cells, and binding and having an effect on known protein interaction.”

Kafka said the company has “an emerging stable of data that gives promise to the opportunity for stapled peptides. We are very encouraged by what we are seeing.”

Aileron is working on one potential lead stapled peptide candidate, the Bim peptide, which plays a role in cell apoptosis. It is currently in preclinical trials and has shown promise in oncology treatments for several solid tumors, including lung and breast cancer and hematology, such as lymphoma, Kafka said. — LaCrisha Butler


Eisai’s Epilepsy Drug Perampanel Sees Positive Phase III Results

Japanese drugmaker Eisai’s investigational epilepsy drug perampanel showed positive results in a Phase III trial, putting the compound on track for an NDA filing as soon as next year.

The compound, which is being developed as an adjunctive treatment for partial seizures in patients with epilepsy, proved to be effective at reducing median seizure frequency and increasing responder rates, the primary endpoints in the double-blind, placebo-controlled study, Eisai said Tuesday.

The results are the first received by the company in a series of three Phase III trials. While the other two studies are ongoing, the company plans to submit marketing applications for perampanel in the U.S. and Europe simultaneously by the end of its fiscal year 2011, which ends in March 2012.

If the drug is approved, it would potentially compete with Lundbeck’s Sabril (vigabatrin), which was approved by the FDA last year to treat complex partial seizures and infantile spasms (DID, Aug. 25, 2009).

GlaxoSmithKline and Valeant Pharmaceuticals’ drug Potiga (ezogabine, also called retigabine) could also be a competitor if it receives FDA approval. An advisory committee voted 13–0 earlier this month in favor of the drug’s efficacy and 11–0 with two abstentions that urinary retention, a side effect, can be mitigated with monitoring (DID, Aug. 12). — David Belian


Baxter Inks $45 Million Deal to Commercialize Kamada’s Glassia

Kamada has entered into a commercialization agreement with Baxter for the rights to market its emphysema treatment, which could be worth up to $45 million.

Baxter will make an upfront cash payment of $20 million for rights to Glassia, a ready-to-use treatment for alpha1-antitrypsin deficiency (AATD), and additional payments of up to $25 million based on other milestones, the companies said Tuesday.
Baxter has committed to purchase $60 million worth of Glassia, a figure that could reach upward of $110 million during the first five years of the agreement. Kamada is also eligible to receive royalties based on sales.

The agreement with Baxter includes an exclusive distribution and manufacturing agreement for Glassia, as well as a technology-sharing agreement for the manufacturing of the liquid treatment. Baxter will be responsible for marketing and distribution of Glassia in the U.S., Australia, Canada and New Zealand.

Israel-based Kamada said in July it expects to gain 10 percent of the $400 million to $500 million AATD market following the FDA’s approval of Glassia last month. Company officials said they also plan to go after the 90 percent to 95 percent of patients with AATD who are undiagnosed. Unlike other treatments, including Talecris’ Prolastin and Baxter’s Aralast, Glassia does not have to be reconstituted (DID, July 6).

Kamada had previously made the distribution deal with ASD Healthcare for the U.S., but that deal was terminated amicably, Kamada spokesman Yaron Cherny told DID.

“ASD is a great partner, but Baxter has some other benefits,” Cherny said, such as its impressive experience in the alpha-1 market. “Baxter is known as the No. 1 company at identifying new patients, and therefore this could be a better deal for the patient community.”

The cooperation with Baxter will enable Kamada financial independence and firmness needed for facilitating the development of the next generation product, the inhaled AAT, Kamada said.

The distribution rights and the licensing agreement do not include the inhaled product, now in Phase II/III clinical trials in Europe, but the companies could strike such a deal on that product in the future. Kamada hopes to apply for FDA approval of that version in 2012. — LaCrisha Butler


NICE Again Refuses Avastin for Colorectal Cancer

The UK’s National Institute for Health and Clinical Excellence (NICE) has again said Roche’s Avastin is not cost-effective for metastatic colorectal cancer (MCC).

The agency, in a preliminary determination made Tuesday, said it could not recommend Avastin (bevacizumab), in combination with chemotherapy, for both first- and second-line use.

NICE originally rejected Avastin for the MCC indication in 2006 (DID, Aug. 23, 2006).

Although Roche submitted a patient access plan as part of the reassessment to justify the cost of bevacizumab, an agency committee felt the plan was complex and administrative costs prohibitively high.

The actual cost of the drug is about $32,100 per patient for a year’s worth of treatment. Roche had offered to pay for Avastin treatment after the first year, as well as a payment to the National Health Service for each person starting first-line treatment.

“As a final consideration, the Committee did not consider bevacizumab represented a sufficiently innovative technology in the treatment of [MCC] because it did not result in a substantial improvement in progression-free or overall survival,” according to the appraisal consultation document.

Cost-effectiveness of bevacizumab presented by Roche was between $162,400 and $167,000 per quality-adjusted life year gained. Under the patient assistance program, however, those figures would drop to between $38,000 and $46,400.

Bristol-Myers Squibb/ImClone’s Erbitux (cetuximab) won NICE’s approval as a first-line MCC treatment in 2009.

NICE set a comment deadline of Sept. 15. The appraisal committee will meet Sept. 28 to make a final decision.

The agency also said it is developing guidance on diagnosis and management of colorectal cancer, expected in July 2011. — Jonathan Block

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Reporters: David Belian, April Hollis, Virgil Dickson, Jim Brocker, LaCrisha Butler

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