Schering’s drug pipeline has become all the more important as recent restructuring efforts has seen the firm divest its dermatology and Jenapharm therapeutics businesses and pull out of R&D in the areas of central nervous system (CNS) and cardiovascular drugs.
Schering already markets the oral contraceptive Yasmin, and big things are expected by the launch of its Yaz and Angeliq products. Angeliq, the only hormone therapy available, combines estradiol with drospirenone. It is currently available in all major European markets. In the US, the Food and Drug Administration (FDA) issued an approvable letter for Angeliq in September 2004.
Requested information was provided to the FDA and a final decision is expected in the fourth quarter of 2005.
Clinical trials with the Yaz have shown high efficacy in patients with symptoms of premenstrual dysphoric disorder (PMDD), a more severe form of premenstrual syndrome (PMS).
In November 2004, Schering received an approvable letter for new oral contraceptive Yaz. The FDA requested additional data to support the clinical benefit of this pill’s dosing regimen – 24 days of active pills followed by four days of placebo pills. These data have been submitted to the FDA and a final decision is expected end of 2005.
Schering also provided details of its therapy for uterine fibroids, Asoprisnil is a novel selective steroid receptor modulator that exhibits unique pharmacodynamic effects in animal models and humans. Asoprisnil, represent a new class of progesterone receptor (PR) ligands that exhibit partial agonist and antagonist activities in vivo.
Phase III clinical trials with Asoprisnil have recently been completed. The results of the trials are currently being evaluated together with Schering’s development partner TAP Pharmaceuticals. Submission for registration of this product is planned in Europe in 2006.
Schering’s refocusing to generate a solid product pipeline in its core areas was undertaken to allow the company to enter a phase of solid growth at a time when its rivals in the pharmaceutical industry would see growth hampered by a less forgiving operating environment, particularly with regard to regulatory oversight.
Schering’s efforts in diagnostic imaging, seems to have made equally solid progress, with the prospect of a new class of blood pool contrast agents to diagnose vascular disease in the offing
The Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion for MS-325 (gadofosveset trisodium), tradenamed Vasovist, specifically used for magnetic resonance angiography (MRA) to diagnose such disorders like aortoiliac occlusive disease in patients with known or suspected peripheral vascular disease (PVD) or abdominal aortic aneurysm (AAA).
Schering AG expects the European Commission’s marketing approval for Vasovist in the fourth quarter of 2005.
One of Schering’s strongest development areas remains in its research into multiple sclerosis and the products it has made available. In the BENEFIT trial, Schering investigated the efficacy and safety of Betaferon (interferon beta-1b) in patients with first clinical symptoms indicative of multiple sclerosis (MS).
In June 2005 the last of the 468 patients completed a two-year investigational treatment with Betaferon. Initial analysis shows high adherence of patients with first clinical signs of MS to Betaferon treatment. The final results of the study will be presented at ECTRIMS end of September 2005.
The company also has a BEYOND trial in which the relative efficiacy of high-dose, high-frequency Betaferon 250 mcg every other day, a BEYOND dose (Betaferon 500 mcg) every other day and glatiramer acetate 20 mg administered subcutaneously every day in patients with relapsing-remitting MS. Recruiting of the study is planned to be completed in 2005, final results will be available in 2007.
One of the more interesting developments within its pipeline is the study in which Campath (alemtuzumab), a monoclonal antibody, for the treatment of MS, which is currently in phase II development. The hope is that Campath could add a novel therapeutic approach to existing MS therapy options.
Multiple sclerosis is a chronic, inflammatory condition of the nervous system and is the most common, non-traumatic, neurological disease in young adults. Multiple sclerosis may affect approximately two million people worldwide.
There are a current crop of disease modifying drugs, which deal effectively in halting the progress of MS although a cure seems unlikely in the near future.
Other disease-modifying drugs currently available include Avonex and interferon beta-1b (Betaferon/Betaseron), as well as glatiramer acetate (Copaxone) and immunosupressants, such as mitoxantrone.
Glatiramer acetate is a synthetic drug that does not occur naturally in the body. It is a random polymer of four amino acids, supposed to mimic a component of human myelin.
Interim results from the Campath study are expected during the second half of 2005, final results are expected to be available in 2007.
For the treatment of Crohn’s disease, a chronic and severe inflammatory disease of the gastrointestinal tract, Schering is developing Leukine (sargramostim) in two phase III programs.
An “Induction trial” (N.O.V.E.L. 4) is evaluating Leukine’s ability to induce clinical remission and response following eight weeks of treatment. In a “Retreatment trial” (N.O.V.E.L. 3), Leukine’s ability to induce clinical remission and response in patients who have relapsed after experiencing initial response or remission is evaluated. Submission for registration in the US is planned for the end of 2006.
In Schering’s oncology business area, the decision to expand its haematology business, developing innovative treatments for solid tumours, looks to have been a good one as it continues to be highly active in cancer treatments and therapies.
First results from the phase III CONFIRM 1 trial with PTK/ZK, a new oral targeted therapy designed to block the growth of blood and lymphatic vessels, demonstrated positive drug effects in patients with metastatic colorectal cancer combined with FOLFOX chemotherapy as a first-line therapy.
Further analysis of the CONFIRM 1 data, including detailed evaluations of overall survival endpoints, is expected in the second half of 2006.
In addition, the CONFIRM 2 trial compares the PTK/ZK combination regimen to FOLFOX-4 alone in patients with metastatic colorectal cancer who have progressed after irinotecan-based first-line chemotherapy. Final overall survival data is expected in mid-2006.
Schering are also testing Bonefos (clodronate), an oral non-amino bisphosphonate intended to reduce the occurrence of bone metastases in the post-surgical (adjuvant) treatment of breast cancer patients.
Bonefos is currently being investigated in the ongoing National Surgical Adjuvant Breast and Bowel Project (NSABP) B-34 study. Final results from that trial, which has completed enrollment of 3,323 women with breast cancer in March 2004, are expected in 2008.
Schering is also in the process of initiating Phase II studies with ZK-EPO, a novel, fully synthetic epothilone in the taxane class of chemotherapy agents.
ZK-EPO is a microtubule stabiliser that preferentially accumulates in the nucleus of cells, predominantly affecting tumour cells, and is not recognized by drug efflux pumps. Microtubules are composed of regular arrays of the protein tubulin and are essential for tumour cell division, the disruption of which is a key anti-cancer strategy. ZK-EPO is more water-soluble than taxanes and does not require a formulating agent such as Cremophor, thereby may reduce side effects.
ZK-EPO is the only fully synthetic epothilone that was designed to overcome multidrug resistance and to combine high efficacy with an improved therapeutic window. Epothilones belong to a class of cytotoxic agents considered to have the potential to replace the taxane class of chemotherapy agents to treat various cancers.
Epothilones inhibit cancer cells by halting cell replication in a similar manner as taxanes. Unlike taxanes, however, epothilones appear to be able to evade some of the cancer cells drug-resistance mechanisms that deprive many cancer therapies of their long-term effectiveness.