Genzyme, a Sanofi company, announced that its Phase III clinical trial of a drug for multiple sclerosis (MS), called Lemtrada (alemtuzumab), led to positive results in patients.

MS is a debilitating neurological disease that affects the nervous system, causing a range of symptoms such as sensory deficits, muscle weakness, and cognitive impairment. Lemtrada is a humanized monoclonal antibody that has already been approved in the EU, Canada, and Australia, and is currently under review by the FDA.

What is Lemtrada?

Lemtrada is a monoclonal antibody that targets a protein on the surface of immune cells called CD52.

By doing so, the drug suppresses the immune system, which is overactive in MS patients and attacks the myelin sheath that covers nerve fibers in the brain and spinal cord. Lemtrada was originally developed as a treatment for leukemia, but then repurposed for MS because of its immunomodulatory properties.

The Phase III trial

The Phase III trial in question, called CARE-MS II, enrolled 840 MS patients with relapsing-remitting MS, the most common form of the disease.

The participants were randomly assigned to receive either Lemtrada or Rebif (interferon beta-1a), an existing drug for MS that is injected under the skin. The trial’s primary endpoint was the annualized relapse rate (ARR) after two years of treatment. The trial also measured disability progression and MRI outcomes as secondary endpoints.

The results

The trial met its primary endpoint, showing that Lemtrada reduced the ARR by 49% compared to Rebif. Specifically, the ARR was 0.22 in the Lemtrada group and 0.39 in the Rebif group.

Moreover, more than twice as many Lemtrada patients were relapse-free for two years compared to Rebif patients, and the time to first relapse was longer with Lemtrada. In addition, Lemtrada showed a significant reduction in the risk of disability progression, as measured by the Expanded Disability Status Scale (EDSS).

At two years, 26% of Lemtrada patients had confirmed disability progression compared to 32% of Rebif patients.

The MRI outcomes also favored Lemtrada. Specifically, Lemtrada patients had a greater reduction in the number of new or enlarged T2 hyperintense lesions, as well as a greater reduction in the mean number of gadolinium-enhancing lesions.

Gadolinium is a contrast agent that highlights active inflammation in the brain.

The safety profile

The safety profile of Lemtrada was consistent with previous trials. The most common adverse events were infusion-associated reactions, infections, and thyroid disorders.

Specifically, 93% of Lemtrada patients experienced an infusion-associated reaction during at least one infusion, but most of these reactions were mild to moderate and resolved within a few hours. Infections were reported in 70% of Lemtrada patients and 64% of Rebif patients, but serious infections were more common with Rebif.

Thyroid disorders, especially autoimmune thyroiditis, were also more common with Lemtrada, affecting 36% of patients, but most of these cases were asymptomatic and resolved with thyroid hormone replacement therapy. Other adverse events, such as malignancies, occurred at a similar rate between the two treatment groups.

The implications

The positive results of the CARE-MS II trial are promising for MS patients who are looking for more effective and convenient treatments.

Lemtrada is given intravenously for five consecutive days in the first year and for three consecutive days in the second year, as opposed to Rebif, which is self-injected three times per week under the skin. Moreover, Lemtrada has a durable effect that lasts for years, as shown in previous trials.

However, the higher incidence of infusion-associated reactions and thyroid disorders with Lemtrada should be carefully monitored and managed, especially in patients with pre-existing autoimmune conditions or infections.

The future

The positive results of the CARE-MS II trial have boosted the prospects of Lemtrada in the US, where the FDA is expected to decide on its approval by December 27, 2020.

If approved, Lemtrada would become the third monoclonal antibody for MS in the US, after Ocrevus (ocrelizumab) and Kesimpta (ofatumumab), both of which target different proteins on immune cells. Moreover, Lemtrada could be used earlier in the treatment of MS, as suggested by the CARE-MS II results, instead of being reserved for patients who have failed other therapies.

Conclusion

The Phase III clinical trial of Lemtrada in MS patients has shown positive results that support its efficacy and safety in reducing relapses and disability progression over two years of treatment.

Lemtrada’s unique mechanism of action and administration schedule make it an attractive option for MS patients who are not satisfied with the currently available treatments. However, the higher risk of infusion-associated reactions and thyroid disorders with Lemtrada should be taken into account when weighing the benefits and risks of the drug.

The approval of Lemtrada by the FDA would expand the treatment options for MS patients in the US and pave the way for further research on monoclonal antibodies in MS.