Schering-Plough's R&D efforts build on the company's existing therapeutic areas, according to the drug maker's R&D update Nov. 1.

"It's important to note how many of our new products and our lifecycle management opportunities actually extend franchises that we already have in the marketplace," Exec VP and President-Global Pharmaceuticals Carrie Cox said.

Schering's strategy of concentrating on areas where it has existing products and experience "makes us stronger competitors in those areas and leverages commercial strengths and infrastructures that we already have," Cox stated.

The company's headline projects fall into a familiar category: antivirals.

Schering is aiming to build on its existing treatments for hepatitis C virus with a new HCV protease inhibitor discovered in Schering's laboratory, Exec VP-Global Development Thomas Koestler reported. Schering markets PEG-Intron (pegylated interferon alfa-2b) and Rebetol (ribavirin) in the U.S.; the two drugs represent the current standard of care for chronic HCV infection.

Schering initiated a Phase II, 300-patient study of the new oral protease inhibitor in October after Phase I results showed a reduction in viral load in patients who failed PEG-Intron therapy when treated with the novel protease inhibitor and PEG-Intron in combination.

The Phase II trial will evaluate the HCV protease inhibitor plus PEG-Intron at different doses and also will compare the dual combination against treatment with the protease inhibitor, PEG-Intron and Rebetol.

Additionally, the company is planning future studies in treatment-naive patients, African Americans and patients co-infected with HCV and HIV.

Launch is expected to come in 2009-2010, Cox said.

Schering's antiviral pipeline also includes the CCR5 receptor antagonist, vicriviroc, for treatment of HIV. Koestler noted the agent is "the first new orally active class for HIV therapy in a decade."

Schering will focus initial registration of vicriviroc on treatment-experienced HIV patients, Koestler said. The decision comes after a study in treatment-naive patients was halted due to virological breakthrough. The discontinuation of the treatment-naive trial was announced Oct. 27.

Schering-Plough ended the Phase II, 92-patient study of vicriviroc plus GlaxoSmithKline's Combivir in treatment-naive patients because a return to detectable viral levels was seen in some patients late in therapy compared to the control regimen of Combivirand Bristol-Myers Squibb's Sustiva .

The Phase II study in treatment-experienced HIV patients is continuing, Schering said.

Koestler maintained vicriviroc is well-suited for treatment-experienced therapy because of its "powerful activity" against drug resistant HIV.

Despite the decision to stop the trial in treatment-naive patients, Koestler said Schering will continue to study vicriviroc within that patient population. The drug maker is planning to initiate another Phase II trial in treatment-naive patients using a different treatment regimen, he said.

"The activity of vicriviroc is at least additive to all other classes of drugs...so it's important for us to find the optimal combination therapy," Koestler said.

Schering is currently "studying vicriviroc in combination with the appropriate background therapies for all patient populations," Koestler reported. "We are focusing on the treatment-experienced patients, but we are also looking at naive, and we intend to expand the program to pediatrics," he added. Launch for vicriviroc is slated for the 2008-2009 period.

In the anti-infective category, Schering's most advanced agent is the oral triazole antifungal Noxafil (posaconazole). The firm is planning to submit a complete response to FDA's "approvable" letter next year, Koestler said. The letter, which was received in June, seeks additional data on the treatment for refractory invasive fungal infections.

Schering is preparing to submit Noxafil for prophylaxis as well. Data from recent clinical trials will be the basis for prophylaxis filings in the U.S. and EU for high-risk patients with graft versus host disease undergoing hematopoietic stem cell transplant and high-risk patients who have prolonged neutropenia.

Schering recently completed two Phase III trials of Noxafil in over 1,200 patients, Koestler reported. Results of the first study showed that Noxafil reduced the incidence of all invasive fungal infections by 50% at any given time in the study. For the primary endpoint of invasive fungal disease in the 16-week study period, Noxafil produced a 67% reduction in incidence of aspergillosis, the company reported.

The second study, which evaluated Noxafil in 602 patients with leukemia or myelodysplastic syndromes at risk of invasive fungal infections, also met its primary endpoint. Data will be presented at the American Society of Hematology annual meeting in December.

Schering also is looking to build on its inflammatory portfolio with golimumab, a fully human antibody offering once monthly subcutaneous therapy for rheumatoid arthritis. Golimumab is licensed from Centocor; Schering holds worldwide marketing and development rights outside of the U.S. and Japan.

The company recently completed Phase II trials with the therapy showing rapid, sustained responses in RA patients. Golimubab has also demonstrated an "attractive safety profile," which is expected to make the drug competitive in the anti-TNF market. Cox projected a launch in 2009-2010.

Schering reported that it is making several advances in its primary care pipeline as well, building on its core cardiovascular and respiratory franchises.

The drug maker is developing a thrombin receptor antagonist for arterial thrombosis that "has a unique mechanism of action by which it will directly block thrombin induced platelet activation," Koestler said. The antithrombotic has potential for use as a single agent or in combination therapy.

The mechanism of action suggests efficacy can be achieved without bleeding liability, so Schering plans to target the therapy to reduce vascular events in high-risk patients, including those with acute coronary syndrome, as well as moderate-risk patients, such as those who have had a myocardial infarction or stroke.

The company has initiated Phase II studies of the thrombin receptor antagonist and is actively planning for Phase III, Koestler said.

"Our data suggests an early onset of action of 90% inhibition within 60 minutes, which may prove to be particularly beneficial to patients in the ER," Cox said.

"It's too early to say what the clinical profile will be, but if it lives up to its potential expectations, this could be a major product for us in the marketplace," she added. Launch could come in 2010-2011.

Of the projects highlighted during the R&D review, Koestler and Cox noted that several were developed in Schering's labs, including Noxafil, vicriviroc and the HCV protease inhibitor. Schering is also turning to licensing to augment its portfolio (see ¹ Also see "Schering Seeks Salvation In External Deals; Hassan Outlines Licensing Plan" - Pink Sheet, 7 November, 2005.).

Faced with a "late-stage pipeline gap," as CEO Fred Hassan noted, Schering has concentrated on maximizing the performance of its existing brands.

"Our core products do have long periods of expected exclusivity and about 85% of our current sales should be protected well through the next decade," Cox said.

Top-line sales growth at Schering is being driven by the company's cholesterol franchise, which consists of Zetia (ezetimibe) and Vytorin (ezetimibe/simvastatin).

In the U.S., Schering's cholesterol franchise ranks among the top three and is continuing to grow, Hassan reported. Cox cited trends towards lower cholesterol goals and combination therapy as evidence of further growth opportunities for the brands. Vytorin offers "a very compelling value proposition. We believe we are very well positioned for the future."

Cox also described the respiratory franchise as an area with a "strong heritage, but also a strong opportunity for the future." She said there is a "vigorous lifecycle management program in place for Nasonex ."

"Two and a half years ago, this brand seemed flat and dull. We were getting advice to dump the respiratory category all together," Hassan said. "Today, we have rejuvenated Nasonex."

Cox also pointed to opportunities with the asthma drug Asmanex (mometasone), the firm's most recent product launch in the U.S. "Asmanex can be positioned along the treatment spectrum in this important market but clearly this is a challenge for us and one that will be difficult [because] there are well-established brands in the market and we are late as an entrant."

"It won't be easy, but we think there is a good place for Asmanex along this spectrum," she said.

Respiratory therapies in the pipeline include pleconaril, which would be the first antiviral for the common cold, a fixed combination of mometasone and formoterol with Novartis and a combination of loratadine ( Claritin ) and montelukast with Merck; all three could reach the market in 2009-2010.

Schering-Plough R&D Pipeline Sticks To Traditional Strengths

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