Genmab's HuMax-CD4 Awarded Fast Track Status From FDA
COPENHAGEN, Denmark, Feb. 21 /PRNewswire-FirstCall/ -- Genmab A/S (CSE: GEN and Neuer Markt: GE9D) announced today that HuMax-CD4 has been designated a Fast Track product by the US Food and Drug Administration (FDA). HuMax-CD4 is in Phase III studies to treat patients with active rheumatoid arthritis (RA) who have failed to respond to treatment with Methotrexate and TNFalpha blocking agents.
Under the FDA Modernization Act of 1997, designation as a Fast Track Product means that the FDA will facilitate the development and expedite the review of a drug if it is intended for the treatment of a serious or life- threatening condition, and it demonstrates the potential to address unmet medical needs for such a condition.
This fast track designation gives Genmab the opportunity to submit a Biologics License Application (BLA) in sequential sections, and have these sections reviewed as they are submitted, thus saving development time. A BLA is the biologic products equivalent to a New Drug Application and is the final stage before a drug is approved for the market by the FDA. Fast track status also opens the possibility for receiving a priority review of the BLA where the review time would be halved to just 6 months.
``Fast Track status accelerates the development time table for HuMax-CD4,'' said Lisa N. Drakeman, Ph.D., Chief Executive Officer. ``There are hundreds of thousands of patients who could benefit from additional treatment options.''
In December 2001, the FDA gave Genmab permission to begin Clinical Phase III trials with HuMax-CD4 for RA. This trial will involve 400 patients at 50 sites in the US and Europe. Genmab will manage this study with its substantial in-house product development team that includes clinical, regulatory and data management staff in the US and Europe.
About Genmab A/S
Genmab is a Danish biotechnology company creating and developing fully human antibodies for the treatment of life-threatening and debilitating diseases. Genmab has a number of products in development to treat cancer, rheumatoid arthritis and other inflammatory conditions such as psoriasis. Genmab aims to create a broad portfolio of new therapeutic products based on its research and development. At present, Genmab's commercial opportunities are based upon research in its own laboratories, as well as via alliances with leading international companies, including Roche, Immunex Corporation, Oxford GlycoSciences Ltd., Medarex, Inc., deCODE Genetics, Scancell, Ltd., Sequenom, Inc., Eos Biotechnology Inc., and Glaucus Proteomics B.V. Genmab has its headquarters in Copenhagen, Denmark and operations in Utrecht, The Netherlands and Princeton, New Jersey in the US. For more information about Genmab, visit www.genmab.com.
Background
Ongoing Pivotal Phase III study - TNFalpha and Methotrexate Failure
In December 2001, Genmab initiated a placebo-controlled, multicenter, Phase III clinical trial in rheumatoid arthritis to treat patients who have failed to respond to TNFalpha inhibitors and methotrexate. The study is expected to treat 402 patients, who will be randomly assigned to one of three treatment groups: placebo, 80mg, or 160mg of HuMax-CD4. These patients will be dosed once at the outset, again at two weeks, then once every four weeks until week 22. The primary clinical endpoint proposed is the mean ACR20 response at 26 weeks.
Rationale for treating patients who fail TNFalpha Inhibitors
A number of clinical and scientific arguments support a potential role for HuMax-CD4 in the treatment of rheumatoid arthritis, and provide a rationale for the Phase III programme. In addition, safety and efficacy data from our Phase I/II and Phase II studies supports our current development plan. We have also submitted safety data to the FDA on 263 patients, the vast majority of whom have received multiple doses of HuMax-CD4.
Failure to Respond to TNFalpha Inhibitors and Incomplete Response -- In clinical trials, once the placebo response level is subtracted, just under 50% of the patients treated with the two TNFalpha inhibitors now in the market, infliximab and etanercept, achieved response at the ACR20 level. This objective standard is used by regulatory authorities to evaluate the effectiveness of rheumatoid arthritis therapies. ACR20 is designed to detect clinically significant change and differentiate active treatment from placebo in clinical trials, but it does not reflect complete response or suppression of disease. However, if ACR70 is used to identify patients who reach near complete suppression of signs and symptoms of rheumatoid arthritis, then in major TNFalpha inhibitors trials the best response is only approximately 15% of patients achieving this result. Additionally, some patients lose treatment effect with continued TNFalpha inhibitor therapy.
While patients may express the same symptoms, rheumatoid arthritis is a diverse disease influenced by genetic factors that can vary from person to person. This helps to explain why not all patients respond to TNFalpha inhibitors and why agents directed to targets other than TNFalpha may be useful in the treatment of patients not responding to TNFalpha inhibitors. HuMax-CD4 is in this category, as it targets a different step in the inflammation cascade, the activation of T cells. Furthermore, in animal arthritis models, antibodies directed against CD4 work synergistically with antibodies to TNFalpha, improving treatment. Therefore, therapy directed to CD4-positive T cells may demonstrate efficacy in patients resistant to TNFalpha inhibitors.
Unmet Medical Need -- Most patients who fail to respond to TNFalpha inhibitors will have ongoing active disease, but currently there are no safe and effective treatment alternatives, since they would already have been treated with one or more of the available disease modifying therapies. Drug treatment options include, either alone or in combination, agents such as cyclosporin A, leflunomide, azathioprine, and d-penicillamine, all with risk of serious toxicity.
Without additional treatment, poor disease control may result in irreversible long-term damage, including joint destruction. Thus, we believe patients who fail to respond to TNFalpha inhibitors represent a major unmet medical need.
HuMax-CD4 Clinical Results to Date
Rheumatoid Arthritis
Completed Phase I/II Study
In our Phase I/II single dose escalation placebo-controlled study involving 35 patients, HuMax-CD4 appeared to be well tolerated in that none of the patients were observed to experience any unexpected drug-related side effects. Furthermore, in this single dose escalation study, 50 per cent of all patients in the four highest dose groups (0.5, 1.0, 2.0 and 4.0 mg/kg) obtained at least an ACR20 response. In addition, one of these patients achieved ACR50, and two achieved an ACR70 response. The same four groups appeared to experience a reduction in the number of swollen joints of more than 60 per cent. (mean) and similarly, a reduction in the number of tender joints of more than 60 per cent. (mean) was observed when evaluating all 16 actively treated patients.
Completed Phase I/II Extension Study
Genmab also conducted an extension of the Phase I/II study to test the safety in continuing HuMax-CD4 with methotrexate treatment. In this open label study, ten patients with active rheumatoid arthritis received a single dose of HuMax-CD4 (4 mg/kg) in combination with low dose methotrexate. The treatment appeared to be well tolerated, in that no serious adverse events and no depletion of T cells were observed. In addition, the patients were found to have signs of clinical efficacy. The number of swollen joints, painful joints and physician's global assessment of disease activity were found to have been reduced, with medians of 57%, 46% and 54%, respectively. Furthermore, two of the ten patients achieved ACR20.
Ongoing Phase II study - Broader Rheumatoid Arthritis Indication
In order to help prevent the debilitating joint destruction that can occur as rheumatoid arthritis progresses, it is becoming common medical practice to treat rheumatoid arthritis patients with low doses of methotrexate relatively early in the course of their treatment. The company is also currently conducting a Phase II study for HuMax-CD4 in a broader arthritis population consisting of patients with moderate to severe arthritis also undergoing methotrexate therapy. If HuMax-CD4 is effective for these patients, we plan to expand the above mentioned Phase III programme in 2003 to include a study in this broader rheumatoid arthritis population. Blinded safety data from this study was presented to the FDA prior to its approval for the Phase III study.
Psoriasis Phase II Results
This small, placebo controlled Phase II study was designed to establish the safety and lowest effective dose of HuMax-CD4 in patients with moderate to severe psoriasis. Eighty-five patients received placebo or one of four dose levels (20, 80, 160, 280 mg) of HuMax-CD4 once weekly for four weeks. After the last treatment, the patients were followed over a period of 11 weeks with the primary endpoint being evaluated at week 7.
Four weeks HuMax-CD4 treatment was safe and well tolerated. PASI was reduced with increased dose levels. Mean PASI was reduced by 12%, 14%, 16% and 24% in the active dose groups, respectively. At the highest dose level, 38% of the patients obtained more than 25% reduction of PASI and half of those patients obtained more than 50% reduction of their PASI.
The efficacy results obtained after just four weeks of treatment indicate that longer treatment would lead to even further reduction of PASI, and Genmab therefore plans to proceed to Phase IIb in psoriasis in the second half of 2002... |
