Johnson & Johnson's next generation non-nucleoside reverse transcriptase inhibitor TMC 125 is on deck to be the first of the firm's four virology NDAs over the next four years, Group Chairman Julie McHugh said during an analyst update outlining the company's growth strategy in New Brunswick, N.J. June 7.

Virology is a leading driver of J&J's business, McHugh added, and the company has established a dedicated business unit to support the development of drugs to treat HIV and hepatitis C.

TMC 125 has the potential to be the first novel NNRTI, an established class of anti-retrovirals for the treatment of HIV, in 11 years. The drug's high genetic barrier to resistance could give it a competitive advantage against established competitors, management noted.

"By next generation, we mean that TMC 125 can be successfully used even if a patient's virus has developed a resistance to all currently approved NNRTIs, including [Bristol-Myers Squibb's] market leader Sustiva ," Tibotec President Roger Pomerantz said. J&J plans to file TMC 125 in the U.S. and in Europe this month, he announced.

The company released Phase IIb data evaluating TMC 125 in heavily treatment-experienced patients with NNRTI resistance and protease inhibitor resistance last year, showing that patients treated with 800 mg of TMC 125 experienced a significantly greater reduction in viral load compared to patients who received an active control.

Pivotal Phase III trials evaluating TMC 125 studied the drug in combination with J&J's protease inhibitor Prezista (darunavir), which was approved last year in treatment-experienced patients, marking the company's entry into HIV (¹ Also see "J&J Enters HIV Arena With Prezista; Darunavir Is Tenth Protease Inhibitor" - Pink Sheet, 3 July, 2006., p. 3).

In the studies, DUET 1 and 2, treatment-experienced HIV patients were treated with a combination of Prezista, TMC 125 and background regimens or Prezista plus placebo and background regimens, with the primary endpoint being proportion of patients with undetectable viral load at 24 weeks. The results are expected to be presented at the International AIDS Society Conference in July.

The firm is planning three additional filings within its virology franchise for the 2009/2010 timeframe: the protease inhibitor telaprevir for hepatitis C in the European Union, a second NNRTI TMC 278 and an investigational drug for multidrug-resistant tuberculosis, TMC 207.

J&J owns rights to telaprevir in Europe and certain other ex-U.S. markets. The company's partner, Vertex, has previously said it expects to file an NDA in the U.S. at the end of 2008 (² Also see "J&J Aims For Virology Leadership, But Pipeline Covers Traditional Strengths" - Pink Sheet, 24 July, 2006., p. 6).

With TMC 278, J&J plans to initiate Phase III trials later this year; the company is studying the NNRTI as a first-line treatment for HIV, with Phase IIb data suggesting comparable efficacy to Sustiva(efavirenz), with superior tolerability, Pomerantz said.

In addition, the firm is continuing to evaluate Prezista in clinical trials to broaden its indications. Ongoing clinical trials include TITAN, evaluating the protease inhibitor in early treatment-experienced patients, and ARTEMIS in treatment-naive populations. In both studies, Prezista is being compared head-to-head to Abbott's Kaletra (lopinavir/ritonavir).

Data from TITAN and ARTEMIS will form the basis of filings for expanded indications, which the company plans to submit sNDAs for at the end of 2007, according to Pomerantz.

J&J used the analyst meeting as an opportunity to outline development and commercialization plans across all of its core therapeutic areas.

Worldwide Chairman of Pharmaceuticals Joe Scodari said the company is on schedule to file regulatory applications for five new compounds by the end of 2007 and an additional seven to 10 compounds between 2008 and 2010.

Aside from TMC 125, other filings planned in 2007 include: CNTO 1275, a first-in-class interleukin-12/23p40 inhibitor, for psoriasis; dapoxetine for the treatment of premature ejaculation in Europe; the long-acting injection formulation of Invega , paliperidone palmitate, with once monthly dosing for schizophrenia; and Zarnestra (tipifarnib) for acute myeloid leukemia.

Dapoxetine and Zarnestra were both deemed "not approvable" by FDA in 2005, Zarnestra based on results of Phase II data and dapoxetine on results of two Phase III trials in 2,614 men. J&J studies have shown no reports of suicidality with dapoxetine, a short-acting selective serotonin reuptake inhibitor. However, the company has said it would need to have a pristine safety profile to be approved by FDA (³ Also see "J&J’s Dapoxetine Has Sound Safety Profile, But Will FDA Be Satisfied?" - Pink Sheet, 11 September, 2006., p. 18).

Since filing the NDA for dapoxetine, J&J has conducted two additional Phase III trials in Europe and Asia in approximately 3,000 men, Group Chairman-Global R&D CNS/Internal Medicine Paul Stoffels said.

The company plans to file dapoxetine in Europe and Canada but did not release a timeline for resubmitting an NDA in the U.S.

Among the six filings timed for 2008 is the Topamax follow-on carisbamate, which has completed Phase II studies in epilepsy. Other potential submissions include golimumab, a self-injectable tumor necrosis factor inhibitor with the potential for dosing once every four weeks. J&J expects to file golimumab initially in three indications, rheumatoid arthritis, ankylosing spondilitis and psoriatic arthritis. Schering-Plough is J&J's development partner for golimumab.

The ongoing late-stage clinical development program for the first-in-class anticoagulant rivaroxaban includes several Phase II and III trials targeting enrollment of 35,000 to 40,000 patients for prevention and treatment of venous thromboembolism and stroke prevention in atrial fibrillation.

Rivaroxaban could change the standard of care as an anticoagulant because it offers an opportunity to be the first single agent that can be used in an IV or subcutaneous formulation in an acute care setting in hospitals and as an oral agent that patients can be transferred onto in the chronic care setting at home, Group Chairman-North America Pharmaceuticals Seth Fischer asserted.

[Correction added June 12: Rivaroxaban is being developed only as an oral product. Fischer indicated the product offers an advantage in that the oral agent can be used both in the hospital and then later in the home.]

J&J will rely on new products to generate robust sales in the face of several upcoming patent expirations for high-revenue products, including for the antipsychotic Risperdal and the anti-epileptic Topamax , which is also used for prevention of migraine.

The company's launch of the patient-controlled transdermal fentanyl product Ionsys is also continuing to face obstacles. FDA approved the opioid in May 2006, but J&J has failed to launch the drug due to manufacturing challenges with the product's electronic delivery device.

Scodari declined to provide a timeline for launching Ionsys, but said, "We believe that we've addressed these challenges, and we hope to have detailed discussions with both the FDA and European regulators regarding what we've learned and our recommendation on how best to move forward."

- Jessica Merrill (j.merrill@elsevier.com)

J&amp;J Growth Plan Calls For Four Virology Filings In As Many Years

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J&J Growth Plan Calls For Four Virology Filings In As Many Years